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Alan Franciscus
Editor-in-Chief
Risk of HCV-Infected Allografts "Serious
Public Health Threat"
Living Donor Liver Transplants Offer Fewer Complications
Than Cadaveric Organs
Metabasis Therapeutics, Inc. Awarded a Two Year,
$2.4 Million Phase II SBIR Grant to Identify Hepatitis C Drugs
Treatment of Acute HCV Requires Expert Timing
Pregnancy May Have Beneficial Effect on Chronic
HCV Infection
Liver transplant recipients over 60 have lower
survival
State Develops Plan to Battle Hepatitis C
Vertex Pharmaceuticals Reports Six-Month Results
from Phase II Clinical Study of Merimepodib (VX-497) in HCV
Drug Earnings Look A Bit Sickly
Life on the Waiting List: Teacher Bides Precious
Time
Massachusetts Prisons Have High Disease Rate
Schering-Plough Gets EU Ok For New Pegintron
Label
New Mexico Inmates to Get Hepatitis Treatment
Pamela Anderson Says Hepatitis C May Kill Her
in a Decade
Fast-Track Review Speeds Japan Pegasys Approval
Laboratory Corporation of America. (LH) To Offer
Liver Fibrosis Assay HCV FibroSure™ Through Exclusive
Relationship With BioPredictive
Schering-Plough Posts Quarterly Loss, Sales
Fall
Tularik Receives FDA “Fast-Track”
Status
Is Acupuncture A Risk Factor For Hepatitis?
Health Officials Report Rise in Hepatitis C
$25 Million Settlement Offered Over Hepatitis
C Outbreak
Problems at Schering-Plough Run Deeper Than
Hassan Thought
EU Removes Requirement for Liver Biopsy For
Pegintron Patients
Possible Settlement of Lawsuits Reached in Hepatitis
C Outbreak
Schering-Plough Provides Grant Supporting Major
New Hepatitis C Research And Education Initiative By American
Academy of Family Physicians
Response to Standard Hepatitis C Treatment Can
Be Predicted As Early As Week 1
Schering-Plough Reports Novel Investigational
Protease Inhibitor
Researchers Identify Essential Component of
Immunity against the Hepatitis C Virus
New Drug Hope for Millions of Hepatitis C Victims
Shorter Interferon/Ribavirin Course Effective
for Chronic Hepatitis C Types 2 & 3
Study Shows 24 Weeks of Pegintron Combination
Therapy As Effective As 48 Weeks In Genotype 2/3 Hepatitis
C Patients
Efficacy in HCV Genotype 4: Unmet Need
Roche Study May Bring Wider Use of Pegasys Hepatitis
C Drug
New Study Investigates Pegasys and Copegus for
the Treatment Of Chronic Hepatitis C in African Americans
New Study Demonstrates Benefits of Hepatitis
C Therapy among Previously Under-Treated Patient Population
Idun Pharmaceuticals Reports Positive Data for
First Oral Clinical Trial in HCV Patients
Drug Hope for Hepatitis C
Pegasys Found Superior to Current Hepatitis
B Treatments
Cirrhotic Patients with Spontaneous Bacterial
Peritonitis
Cultures Of Human Fetal Hepatocytes
Idenix Pharmaceuticals Presents Positive 1-Year
Data On Telbivudine(LdT) For The Treatment Of Chronic Hepatitis
B
Management Of Hepatocellular Carcinoma Larger
Than 10 Cm
Severe Hepatitis C-Related Liver Damage Following
Liver Transplantation
Health-Related Quality of Life in Long-Term
Liver Transplant Survivors
Survival of Recipients Of Liver Grafts From
Donors Over 80 Years
Virus-Related Muscle Damage Tied To Chronic
Fatigue
Transplant Extends Survival in Liver Cancer
Patients
Designer Transplant Drug Shows Promise In Monkeys
Compound May Block Organ Rejection Without Side-Effects
October 15th, 2003
Risk of HCV-Infected
Allografts "Serious Public Health Threat"
Peggy Peck
Limitations in donor screening combined with outmoded donor
tissue sterilization procedures suggest that about 300 hepatitis
C virus (HCV)-infected musculoskeletal tissue specimens are
distributed by U.S. tissue procurement centers each year,
according to the results of a study presented here at the
41st annual meeting of the Infectious Diseases Society of
America.
Lennox Archibald, MD, medical director
of Regeneration Technologies in Alachua, Florida, said that
the Food and Drug Administration (FDA) currently "has
no approved test for postmortem presence of HCV in donor tissues.
Our research suggests that there could be up to 300 infected
tissue specimens distributed each year in the U.S. The multiple
infections this could cause in the recipient population “and
those who have contact with them — presents a serious
public health threat." Dr. Archibald supervised investigations
of allograft infection outbreaks while serving as a medical
epidemiologist with the Hospital Infections Program at the
Centers for Disease Control and Prevention from 1995 to 2002.
He noted that about 18,000 cadaveric donors
provide 650,000 allografts for transplantation often cartilage
for joint surgeries--each year. Thus, tissue from a single
infected donor could be distributed among dozens of recipients.
Serological tests used to screen tissue
donors for HIV antibody and hepatitis B virus (HBV) surface
antibody are very sensitive, but serology for HCV is not as
sensitive (97%), Dr. Archibald said. This is clinically worrisome
because data from first-time blood donors suggest that the
seroprevalence of HCV is markedly higher, 0.4%, than seroprevalence
of HIV (0.02%) or HBV (0.2%). Thus, he theorized that HCV
prevalence among tissue donors would also be higher. He said
an analysis of data from tissue procurement agencies suggests
that HCV is actually more common almost three times more common--among
tissue donors than among first-time blood donors.
In the study, Dr. Archibald and colleagues
obtained seroprevalence data collected from July 1996 to June
2001 from 39 U.S. tissue procurement agencies. HIV, HBV, and
HCV tests were performed on postmortem blood after standard
donor screening, which included medical/social history, physical
examination, and review of medical records. Positive HIV Ab
was confirmed by Western Blot, HBsAg by neutralization, and
HCV by recombinant immuno-blot assay.
Dr. Archibald used published anti-HCV
sensitivity data for clinical samples to estimate the annual
number of HCV-infected tissue donors that might not be detected
on initial screening.
The 39 agencies performed initial serology
on a total of 19,300 cadaveric tissue donors. That sample
represents about 21% of the tissue donors in the U.S. during
the same period. Seroprevalence rate for HCV Ab was 1.06%
compared with 0.03% for HIV and 0.29% for HBsAg, he said.
Thus, about five HCV-infected tissue donors
would be missed and 180 HCV-infected allografts distributed.
But that estimate does not include the number of tissue donors
that may be in the "window period" during which
serology would not detect infection. So a more accurate estimate,
he said, "is about 300 to 350 infected allografts each
year."
A sterilization procedure that included
viral inactivation would reduce this risk, but Dr. Archibald
noted that the FDA does not currently require that tissue
processors use such procedures.
"The significance of this study
is that, clearly, ongoing testing of cadaveric tissue does
not exist and this unique investigation has determined a significant
rate of hepatitis C infection among donors," Christopher
Woods, MD, director of the microbiology laboratory at the
Durham Veterans Administration Medical Center in North Carolina,
told Medscape. Dr. Woods was not involved in the study.
He added, "We can't underestimate
the importance of making sure that tissues that are being
transplanted into our desperately ill patients are, in fact,
healthy tissues. [This study] is a very important study."
Millions of people have been unknowingly
infected with hepatitis C, some of them from contaminated
blood during transfusions, according to health officials.
"We know that many people are infected
with hepatitis C and are unaware that they have the disease,"
said newly appointed US Surgeon General Dr. David Satcher.
"Unfortunately, many of them cannot
be readily identified because the disease does not cause symptoms
until it is far advanced."
"Many with hepatitis C virus have
no reason to believe they are infected," researchers
say. "Many of those at high risk are average people --
middle-aged housewives who had a cesarean section delivery,
young adults who had transfusions as high-risk babies or middle-aged
men who served in Vietnam."
It is believed that millions are infected
with hepatitis C by transfusions.
Hepatitis C is a potentially deadly disease
that infects the liver, causing extreme fatigue, nausea, loss
of appetite and abdominal pain. It can eventually cause cirrhosis
of the liver and death.
It is considered a silent epidemic because
many people don't develop symptoms for decades. The Centers
for Disease Control and Prevention (CDC) in Atlanta estimates
that 40 to 70 percent of those exposed to tainted blood become
infected with hepatitis C. Symptoms of Hepatitis C are nausea
and vomiting, weakness, fever, muscle and joint pain, yellowing
of eyes and skin, dark urine and tenderness in upper abdomen.
It is spread most commonly through intravenous
drug use, blood transfusions and organ transplants. It can
also be spread through sexual contact, although it is a less
likely means of transmission.
Satcher said that those who were infected
from contaminated blood transfusions could be tracked through
hospital and blood bank records.
An estimated 8,000 to 10,000 people die
from hepatitis C each year.
Back to top
Living
Donor Liver Transplants Offer Fewer Complications Than Cadaveric
Organs
by Megan Rauscher
Living donor liver transplantation (LDLT)
is associated with a lower rate of serious complications and
rejection and may have a slightly higher survival than orthotopic
liver transplantation, according to intermediate term morbidity
and mortality data from 92 patients who underwent LDLT at
the University of Rochester in New York between 2001 and 2002.
The study represents the largest single-center
study of LDLT in the U.S., Dr. Parvez S. Mantry told Reuters
Health. He presented the results Monday during the 68th Scientific
Meeting of the American College of Gastroenterology in Baltimore,
Maryland.
"From the donor standpoint, we published
data separately showingthat it is an extremely safe procedure,"
Dr. Mantry told Reuters Health.
In the current study, most recipients tolerated
the procedure "very well," he said, with 86% not
experiencing any significant complications, and the survival
rate was "pretty good," with 92% of patients alive
at 6 months.
"Although I published just the intermediate
term mortality, we are seeing that patients who underwent
LDLT even two or three years ago are for the most part doing
quite well," Dr. Mantry told Reuters Health.
The biliary and vascular complication rate
for the Rochester LDLT cohort (6.7% and 2.2%, respectively)
is lower than that reported nationally (22% and 9.8%, respectively),
the research team notes in a meeting abstract.
"The only condition where we have
to be a little watchful, and again that is evolving, is chronic
hepatitis C," Dr. Mantry said. "These patients may
have a higher morbidity from LDLT although that data is not
yet completely assimilated."
"LDLT, from my perspective as a hematologist,
is a very good alternative to cadaveric liver transplantation
mainly because the shortage of organs is so great," Dr.
Mantry said.
New York State has the largest waiting
list in the country but the least number of organs supplied
from cadavers so there is a "huge gap between supply
and demand," he explained, "which is why we like
to bank on living donor liver transplantation."
Dr. Mantry said he believes that LDLT is
"certainly going to catch on and will definitely be a
large part of liver transplantation in the future."
Back to top
October 16th, 2003
Metabasis
Therapeutics, Inc. Awarded a Two Year, $2.4 Million Phase
II SBIR Grant to Identify Hepatitis C Drugs
Metabasis Therapeutics, Inc. announced
today that it has been awarded a two year Phase II Small Business
Innovation Research (SBIR) grant of up to $2.4 million by
the National Institute of Allergy and Infectious Disease (NIAID)
entitled "Liver-Targeted Prodrugs for the Treatment of
Hepatitis C."
The grant supports research at Metabasis
focused on identifying potent, efficacious and safe drugs
for the treatment of hepatitis C patients using the company's
proprietary HepDirect(TM) technology.
The HepDirect technology is a prodrug technology
developed and patented by Metabasis that enables liver targeting
of the biologically active form of a wide variety of new and
existing drugs. Liver targeting can increase liver drug levels
and reduce peripheral exposure to the active compound and
thereby result in more effective and safe drugs for treating
liver diseases.
It is estimated that greater than 170 million
people are infected with hepatitis C worldwide. Despite recent
improvements in current therapies, a large segment of this
population is still not adequately treated. Nucleosides represent
a class of compounds commonly used to treat viral infections
such as hepatitis C. To date, however, few nucleosides other
than the marketed drug ribavirin have proven effective against
hepatitis C. Poor efficacy is attributed in many cases to
poor conversion of the nucleoside to the corresponding nucleoside
triphosphate, or NTP, which is the active form of the drug.
Metabasis believes its HepDirect technology can overcome this
limitation and lead to higher NTP levels in the liver while
simultaneously decreasing NTP levels outside of the liver,
which in some cases will result in improved safety.
Mark Erion, Executive Vice President of
Research and Development stated, "We are excited to receive
this award from NIAID. We plan to use the funding to expand
our nucleoside and HepDirect prodrug libraries, which we believe
will help us to identify new inhibitors of an enzyme important
for hepatitis C viral replication. The funding will also support
our efforts to further develop a cell-based screen that we
believe will provide information useful for selecting a development
candidate. Our HepDirect prodrug technology is being used
with Metabasis' drug candidates for hepatitis B and primary
liver cancer and we believe it will prove useful for targeting
drugs designed to treat hepatitis C infections to the liver."
Metabasis Therapeutics, Inc. (www.mbasis.com)
is a privately held, biopharmaceutical company that develops
proprietary products principally for the treatment of liver
and liver-related metabolic diseases. Metabasis has expertise
in the fields of nucleoside / nucleotide chemistry and metabolism,
liver biology and liver-specific drug delivery. Metabasis
has discovered and developed a new class of drug candidates
for treating diabetes that act to lower liver glucose production
in diabetic patients. The first drug candidate from this program,
CS-917, is being developed in collaboration with Sankyo Co.,
Ltd. and is currently undergoing clinical testing. Metabasis
has also developed its HepDirect technology that allows liver-specific
delivery of new and existing drugs. Two novel drug candidates
derived from the HepDirect technology are in clinical testing:
a drug for hepatitis B called Hepavir B, developed in collaboration
with Ribapharm, Inc., and a drug for primary liver cancer
called MB7133, to which Metabasis retains exclusive rights.
Back to top
Treatment
of Acute HCV Requires Expert Timing
Peggy Peck
If acute hepatitis C (HCV) is left untreated, a high number
of patients who are asymptomatic after exposure will spontaneously
clear the virus within two to four months of infection, according
to David Oldach, MD, from the University of Maryland School
of Medicine in Baltimore.
Dr. Oldach, who spoke during a symposium
on hepatitis C management controversies at the 41st annual
meeting of the Infectious Diseases Society of America, said
that one recent published report indicated that the clearance
rate in untreated individuals is "as high as 52%."
However, he said that waiting for the virus to clear spontaneously
can be problematic because if treatment is delayed too long,
it is unlikely that the virus will respond to therapy. The
issue boils down to this question, he said: "How early
is too early, and how late is too late?"
Given the high rate of spontaneous clearance,
Dr. Oldach said there are good data that suggest treatment
"before two to four months is probably too early."
He noted that for most patients treatment should follow "a
robust immune response" and he added that HCV-specific
proliferative responses are "necessary, but not always
sufficient for clearance [of HCV]."
He cited an ongoing University of Maryland
study of healthcare workers exposed to HCV through needle-stick,
which suggests that there are some factors that predict spontaneous
clearance of HCV: "Young females with symptomatic infection
are most likely to clear."
Just as treatment before two to four months
is too early, Dr. Oldach said that "if you wait to treat
until six months, you've probably waited too long." Studies
indicate that the likelihood of achieving a viral response
begins to decrease by six months. Thus, he said, treatment
should ideally take place between four and six months after
infection.
Once the patient and physician have agreed
that treatment is indicated, Dr. Oldach said the next issue
is "what therapy should be used?"
Most large studies were conducted in populations
with chronic infection, so there is little evidence to guide
treatment choices, he said.
Citing four studies that were conducted
in acute posttransplant HCV, Dr. Oldach said that high dose
5-10 million IU/day) interferon-alpha monotherapy for two
weeks followed by 24 weeks at standard dose (3 million IU
three times per week) achieved the most robust response. But
"the addition of ribavarin did not affect outcome,"
he said.
Raymond T. Chung, MD, associate professor
of medicine at Harvard Medical School in Boston, Massachusetts,
said that aside from acute HCV, a second difficult treatment
population is made up of patients who have HIV as well as
chronic HCV. With these patients, the clinician needs to determine
not only when and how to treat but also when and how often
to biopsy, because some data suggest that coinfection increases
the progression of fibrosis in the liver.
Dr. Chung said that he tracks fibrosis
by developing a fibrosis index that is based on the change
in fibrosis score between the first and second biopsy, divided
by the time between biopsies. When this index increases, he
recommends initiation of treatment.
Once treatment is initiated in coinfected
persons, Dr. Chung said that patients should be closely monitored
because "early viral response has a strong negative predictive
value. Thus, if the patient fails early, he or she is likely
to fail late."
When selecting an agent to treat coinfected
individuals, Dr. Chung said he recommends pegylated interferon,
which he said "should now be considered the standard
of care for coinfected individuals."
Eliot W. Godofsky, MD, assistant clinical
professor of medicine at the University of South Florida in
Tampa, said the difficult treatment decisions especially treatment
of coinfected individuals might be eased with "a noninvasive
test for markers of fibrosis." But Dr. Godofksy, who
chaired the HCV controversies symposium, said such tests were
"just in the investigational stage and clearly not ready
for prime time."
Back to top
Pregnancy
May Have Beneficial Effect on Chronic HCV Infection
Medscape
Pregnancy and parturition may enhance the natural resolution
of hepatitis C virus (HCV) RNA in women with chronic HCV infection,
according to a report published in the October issue of the
Journal of Medical Virology (J Med Virol
2003;71:205-211).
The findings are based on a study of 22
pregnant and 120 nonpregnant female patients infected with
HCV. Patients in both groups tested positive for anti-HCV
antibodies and for HCV RNA.
In the pregnant group, two women lost HCV
RNA permanently after parturition and one lost HCV RNA intermittently,
Dr. Masashi Mizokami, from Nagoya City University Graduate
School of Medical Sciences in Japan, and colleagues note.
In contrast, in the control group, one woman lost HCV RNA
permanently and one lost it intermittently (p = 0.03).
At 3 months after parturition, women who
lost HCV RNA were more likely than those with persistent HCV
RNA to have an HCV core protein level < 15 fmol/L (p =
0.02).
"The mechanism by which pregnancy
and delivery influence HCV viremia levels is not well understood,"
the authors note. However, it may be immune-mediated and result
from the post-delivery "rebound of the Th1 response after
Th2 shift during pregnancy."
Taken together, the findings suggest that
"pregnancy and parturition may improve the prognosis
in women with chronic HCV infection," they add.
Back to top
Liver Transplant Recipients over 60
Have Lower Survival
gastrohep.com
Older liver transplant recipients have lower survival than
younger patients, find physicians in the November issue of
the American Journal of Transplantation (Am J
Transplant 2003; 3(11): 1407-12).
Older age is not considered a contraindication
for liver transplantation. However, age-related morbidity
may be a cause of mortality.
In this study, physicians from Spain evaluated
survival and incidence of post-transplant complications in
111 adult liver transplant recipients.
The team divided patients into 2 groups
according to age:
Patients younger than 60 years (n = 54)
Patients older than 60 years (n = 57)
The doctors found that older patients were
more frequently transplanted for hepatitis C and hepatocellular
carcinoma. Their liver disease tended to be less advanced.
Malignancy as the cause of death:
Older patients = 21%
Younger patients = 2%
However, after transplantation these patients had significantly
lower survival, when compared to younger patients.
The team determined that higher age was
independently associated with mortality.
In addition, the incidences of de novo
neoplasia and nonskin neoplasia were
higher in older patients.
In this study, the team found that malignancy
was the cause of death in 2% of patients under 60 years, compared
with 21% of patients over 60 years.
Higher age and smoking were independently
associated with a greater risk of dying of de novo neoplasia.
Dr Ignacio Herreroa's team concluded, "Older
liver transplant recipients have a significantly lower survival
than younger patients".
"Malignancy is responsible for this decreased survival."
Back to top
State Develops Plan to Battle Hepatitis
C
The Hawaii Department of Health is releasing a newly developed
plan that addresses issues of surveillance, education, prevention
and treatment of hepatitis C, health officials said. "Because
of the similar risk factors between viral hepatitis, HIV and
sexually transmitted diseases, we have been working to develop
a program that integrates hepatitis prevention, particularly
hepatitis C, into existing public health department prevention
services and programs," said Peter Whitica, chief of
the department's STD/AIDS Prevention Branch.
Hawaii physicians and laboratories have
reported more than 5,000 cases of HCV since 1997, but since
the virus does not always produce symptoms, as many as 20,000
in the state could be infected, officials said.
Back to top
October 17th, 1003
Vertex Pharmaceuticals
Reports Six-Month Results from Phase II Clinical Study of
Merimepodib (VX-497) in HCV
Merimepodib Demonstrated Proof-of-Mechanism (Tolerability
and Clinical Activity) in Combination with Pegylated Interferon
and Ribavirin - Vertex Pharmaceuticals Incorporated (Nasdaq:VRTX)
today reported encouraging results from a six-month interim
analysis of an ongoing Phase II clinical trial with its novel
drug merimepodib (VX-497) for the treatment of hepatitis C
virus (HCV) infection. This 31-patient study is designed to
evaluate the safety, tolerability and clinical activity of
merimepodib administered in combination with pegylated interferon
(peg-IFN) and ribavirin in HCV patients who were non-responsive
to treatment with a previous course of interferon and ribavirin.
At six months, merimepodib met its primary endpoint of safety
and tolerability and was not associated with any serious adverse
events. At six months, merimepodib also met its secondary
endpoint of clinical activity and demonstrated a statistically
significant antiviral response in combination with pegylated
interferon and ribavirin.
"In this six-month interim analysis, merimepodib was
well tolerated and showed a statistically significant dose-dependent
antiviral effect, suggesting that merimepodib may enhance
the antiviral activity of pegylated interferon and ribavirin,"
stated John J. Alam, M.D., Senior Vice President of Drug Evaluation
and Approval. "Based on the tolerability and clinical
activity of merimepodib observed in the interim analysis of
this study, we believe proof-of-mechanism for merimepodib
in treatment-refractory patients has been obtained. The complete
analysis, which will include 12-month treatment and six-month
post-treatment data, will be used to guide the clinical path
of merimepodib going forward."
"Within the limitations of the size
of this study, we are encouraged by the tolerability and additive
antiviral activity that merimepodib demonstrated in patients
who were non-responsive to previous combination therapy,"
stated Dr. Patrick Marcellin, Professor of Medicine at University
of Paris VII, and the lead investigator for the study. "The
main goal of HCV treatment is to clear the virus
from patients. The addition of merimepodib to a standard-of-care
regimen appears to increase the proportion of treatment-refractory
patients who show a viral response at six months, representing
a clinically important finding. "
Study Design
The Phase II, double-blind, placebo-controlled, randomized
study is designed to evaluate the safety and tolerability
of two dose regimens of merimepodib in combination with peg-IFN
and ribavirin in patients with HCV genotype 1 who were non-responsive
to interferon-alpha and ribavirin therapy. The secondary objective
of the study is to assess the pharmacokinetics and clinical
activity of merimepodib. The study is being conducted in Europe.
Patients enrolled in the
study had previously received a minimum of 12 weeks of IFN
and ribavirin treatment without achieving undetectable viral
RNA (vRNA)at any time point. After the initial six months
of the trial, patients had the option to extend treatment
for an additional six months. Collection of 12-month end-of-treatment
data and six-month post-treatment sustained virologic response
data is continuing.
Vertex anticipates that when the study is complete, the full
trial results will be presented at a medical conference.
Merimepodib is one of several drug candidates
in Vertex's product portfolio that the Company is developing
independently in the areas of infectious disease, autoimmune
disease, inflammation and genetic disorders. Based on results
from ongoing studies, as well as an analysis of market opportunity,
Vertex expects to prioritize two drug candidates from this
portfolio for full development and
commercialization in high-value markets served by specialists.
At the same time, Vertex will continue to pursue strategic
alliances to maximize the near-term and downstream commercial
value of certain research and clinical development programs.
Vertex currently retains all worldwide development and commercial
rights for merimepodib.
About Merimepodib
Merimepodib is a small molecule, orally administered inhibitor
of the enzyme inosine monophosphate dehydrogenase (IMPDH).
IMPDH inhibition leads to a reduction in intracellular guanosine
triphosphate (GTP), a molecule required for DNA and RNA synthesis.
Recent reports in the medical literature
suggest that IMPDH inhibitors such as merimepodib may enhance
the antiviral activity of ribavirin in vitro by depleting
GTP and increasing the rate of incorporation of ribavirin
into viral RNA, rendering the virus nonfunctional (1). These
insights provide a mechanistic interpretation for the antiviral
activity observed clinically when merimepodib is added to
ribavirin-containing HCV therapies. IMPDH inhibition may therefore
represent an attractive strategy for increasing the sustained
viral response rate in HCV patients, the principal goal of
treatment.
Previous Studies of Merimepodib
Merimepodib has been evaluated in two previous short-term
studies in HCV patients. Vertex previously reported data from
a 28-day Phase II study to evaluate the safety, tolerability
and clinical activity of merimepodib combined with interferon-alpha
in treatment-naive HCV patients. The viral load data from
this study showed a trend toward enhanced antiviral activity
in patients treated with merimepodib combined with interferon
as compared to patients receiving interferon alone.
Vertex has also conducted a 28-day Phase
II study of merimepodib administered as a monotherapy to HCV
patients who were non-responsive to prior treatment with interferon-alpha.
Results from this study showed that merimepodib was well tolerated
and appeared to reduce levels of serium alanine aminotransferase
(ALT), a marker of liver inflammation.
About HCV Infection
HCV infection is a serious disease that causes inflammation
of the liver, which may lead to fibrosis and cirrhosis, liver
cancer, and ultimately, liver failure. Chronic hepatitis C
infection afflicts approximately 2.7 million people in the
U.S., many of whom are unaware of their infected status. HCV
may go undetected for up to 20 years following initial infection.
Worldwide, the disease strikes as many as 185 million people.
Each year, 8,000 to 10,000 people in the U.S. die from complications
of HCV. Current treatments have been effective for only 40
to 60 percent of patients chronically infected with genotype
1 HCV, the most difficult viral strain to treat and the most
common form in the U.S. Patients who are non-responsive to
current HCV therapy have limited treatment options, and clinical
experience shows that only a very low proportion of such patients
achieve a sustained viral response with subsequent treatment
regimens.
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology
company committed to the discovery and development of breakthrough
small molecule drugs for serious diseases. The Company's strategy
is to commercialize its products both independently and in
collaboration with major pharmaceutical partners. Vertex's
product pipeline is principally focused on viral diseases,
inflammation, autoimmune diseases and cancer. Vertex's first
approved product is the HIV protease inhibitor Agenerase (amprenavir),
which Vertex co-promotes with GlaxoSmithKline.
Vertex Safe Harbor Statement
This press release may contain forward-looking statements,
including statements that i) that merimepodib may enhance
the antiviral activity of pegylated interferon and ribavirin;
ii) that proof-of-mechanism has been obtained based on interim
data from Vertex's clinical study; and iii) that Vertex will
prioritize two drug candidates from its portfolio for independent
development and commercialization in high-value markets served
by specialists. While management makes its best efforts to
be accurate in making forward-looking statements, such statements
are subject to risks and uncertainties that could cause Vertex's
actual results to vary materially. These risks and uncertainties
include, among other things, the risk that i) the six-month
interim analysis of the study may not be indicative of the
12-month analysis; ii) data suggesting proof-of-mechanism
may not be confirmed by 12-month data, or the results of this
small Phase II study of merimepodib may not be indicative
of the results that would be obtained in a larger trial; iii)
Vertex's drug development programs may not proceed as planned
due to partnership, technical or patient enrollment issues,
and other risks listed under Risk Factors in Vertex's form
10-K filed with the Securities and Exchange Commission on
March 31, 2003.
Agenerase is a trademark of the GlaxoSmithKline
group of companies.
(1) Zhou, S. et al. (2003) The effect of
ribavirin and IMPDH inhibitors on hepatitis C virus subgenomic
replicon RNA. Virology 310: 333-342.
Vertex Contacts:
Lynne H. Brum, Vice President, Corporate Development and Communications,
(617) 444-6614
Michael Partridge, Director, Corporate Communications, (617)
444-6108
Jaren Irene Madden, Media Relations Specialist, (617) 444-6750
Back to top
October 17th, 2004
Drug Earnings
Look A Bit Sickly
Ed Silverman
Just a few years ago, drug stocks were treated like gold.
And for good reason.
Since the results of drug companies aren't
tied to economic cycles, the industry was viewed as a nice
hedge against a soft economy. Moreover, billion-dollar sellers
were still streaming out of many labs.
Not anymore.
This year, the pharmaceuticals group is
likely to generate earnings growth of just 0.9 percent, half
of last year's performance, according to Michael Krensavage,
an analyst at Raymond James.
"Many of the big names have been left
behind in the rally since last spring," said Brandon
Carl, an analyst at BB&T Asset Management. "Basically,
a lot of people are worried about competition from generic
drugs."
Investors will get a glimpse of how the
major drug companies are faring this week when Merck, Pfizer,
Schering-Plough, Wyeth and Bristol-Myers Squibb report third-quarter
earnings. Johnson & Johnson last week posted a 20 percent
increase in profit, though it acknowledged it is in a cost-cutting
mode.
Between them, these companies form the
heart of the U.S. drug industry and employ tens of thousands
of people in New Jersey.
The biggest drag on the sector is Schering-Plough,
which last year lost patent protection for Claritin, the allergy
medicine, and faces increased competition for its hepatitis
C treatment. Recently, the Kenilworth drug maker announced
a restructuring.
But the subsequent arrival of cheaper generics
is the big reason the company is expected to report third-quarter
earnings of 10 cents a share, a 66 percent drop compared with
the previous year, Krensavage said.
By the same token, Schering-Plough shares
have been battered for so long that Tim Anderson, an analyst
at Prudential Financial, said he believes the company is undervalued,
at least for the longer term. In particular, he points to
sales potential for Zetia, a cholesterol drug.
Schering-Plough "should be one of
a small handful of pharmaceutical stocks with naturally occurring
revenue and earnings growth," he wrote in a note to clients.
"This growth will likely be driven largely by Zetia,
and a (planned) combination of Zetia and Merck's Zocor."
The outlook for Merck, by contrast, is
less certain. The Whitehouse Station drug maker recently spun
off Medco Health Solutions, the pharmacy-benefits manager,
which means investors will see earnings from Merck reflecting
a pure pharmaceuticals entity.
But Merck faces concern about the prospects
for cholesterol drug Zocor, its biggest-selling medicine.
Year-over-year sales are expected to decline, according to
Anderson. Meanwhile, Zocor faces generics in other countries
and the recent launch of AstraZeneca's Crestor here.
"We remain skeptical on Merck, because
prescription data suggest the company needs accelerated sales
to hit its earnings growth target of 10 percent this year,"
wrote Krensavage, who looks for Merck to report third-quarter
earnings of 83 cents, up 6.4 percent.
He added Merck prescriptions filled through
retail and mail-order pharmacies fell 9.5 percent through
August, and dollar-valued sales rose 1.3 percent, citing data
from NDC Health, a market-research firm.
Similarly, analysts are cautious about
Pfizer, which sells Lipitor, the leading cholesterol treatment,
because of fresh competition. There is also a potential rival
for Viagra, another big seller. Krensavage looks for earnings
of 38 cents, down 4.5 percent from a year ago.
On an upbeat note, Krensavage said he forecasts
Bristol-Myers Squibb will report an 11 percent increase in
earnings, to 41 cents. The performance is mostly due to the
poor showing a year ago, but also strong results from treatments
for HIV and schizophrenia.
Wyeth is expected to report third-quarter
profit of 55 cents, up 17 percent, said Krensavage, whose
forecast is 5 cents less than the consensus of other drug-industry
analysts. The bright spots include rising sales of a heartburn
drug and an anti-depressant.
But declining sales of hormone replacements,
which have been linked to cancer, continue to plague the Madison-based
drug maker. He expects sales of the Premarin product line
to show a sales drop of $285 million, or 32 percent, from
a year ago.
Back to top
Life on
the Waiting List: Teacher Bides Precious Time
by Jack Slater
That Saturday morning was pleasant— almost too pleasant.
It was May 26, 2002. My wife and I were in our kitchen in
Ballard, about to make a batch of gazpacho to welcome the
coming summer. I was holding a tuna-salad sandwich, wrapped
in plastic, which I had just bought at the corner store.
We heard the rattle of the mailbox, so I went downstairs,
sandwich in hand. I opened the mailbox door and there it was—the
letter I had been expecting for almost two months. I pulled
it out and stared at the envelope. It seemed to glow in my
hand. I kissed it and said a quick prayer for the hope it
had to offer. For it to say I had been placed on the waiting
list for a liver transplant.
I HAVE HEPATITIS C, a nasty, blood-borne virus that attacks
the liver,eventually killing it and the person in whom the
liver resides. By that May morning, I had endured six months
of tests in one of life’s more ironic contests: trying
to prove I was healthy enough to earn my place in line for
a donated organ.
The only known treatment for “hep C” involves
daily injections of interferon. The side effects are nasty
and the cure rate is roughly 20 percent. My disease is sufficiently
advanced to make the odds of a cure much lower and the harsh
treatment not worth the odds. Now my only hope is if somebody
out there dies the right kind of death: one that leaves the
liver intact. The person who dies needs to be healthy—and
needs to die when I’m healthy enough to be approved
for, and survive, a grueling surgery. The person needs to
have my blood type, be about my size and have had the foresight
and kindness to register the desire to be an organ donor.
Of course, I wish you a long and happy life. But if that doesn’t
happen, well, someone out there could use your lungs, heart,
valves, eyes, skin, bone, tendons, kidneys and liver. It’s
an amazing world we live in.
I HAD NO SYMPTOMS when I was diagnosed with hep C in 1997.
That same year I was hired to teach history at Seattle’s
Franklin High School, a job that brought my life full circle.
I learned the gift of gab selling men’s shoes at my
father’s store in West Palm Beach, Fla. I was a history
and education major in college and taught adult ed for a year
before I hit the road, Jack Kerouac style. I stumbled into
acting, which I did for 20 years: movies, television, commercials,
a bit of stand-up political humor. It was fun while it lasted,
but no way for a grown man to live. I had long harbored this
notion of moving to Seattle, where I could drink good beer
at the Virginia Inn and play softball at Green Lake. And in
1991, I did just that, after falling in love with the woman
who has been both my dream and my wife for 12 years. After
teaching at the King County Jail and as a substitute teacher
in the Seattle schools, I landed this great gig at Franklin.
Teenagers are fun and exasperating and bored by un-hip education.
Reading is slow; computer games brilliantly quick. It doesn’t
help that many parents are chronically broke or that many
teachers are close to broke.
But teaching has its perks. It feels righteous to chaperone
the prom. We hear great concerts by the jazz band and see
wonderful stage productions. We see talented kids mature and
add a few inches from year to year. We miss them when they
graduate.
Teaching history has been made even more exciting by world
events. Each day, it seems, the front page offers earthshaking
news that can be connected to the culture, social movements
and wars of the past, that connects people in the Middle East,
Korea and Texas. Every chance I got, I taught African-American
history. It’s in our face every day. We must learn it
well. All of us.
So when I was told I had hep C, I quit drinking ‘doctor’s
order’ and poured myself into teaching. For almost five
years, I was happy and symptom-free.
THEN, IN LATE 2001, I GREW TIRED. Impossibly tired. School
starts at 7:45 a.m.; I had trouble getting out of bed in time.
Driving home after school, I found myself dozing at red lights.
A medication I was taking sent me on frequent trips to the
bathroom; it’s not cool to be late for class or to leave
in the middle.
By May 2002, I had to stop working. I was calling in sick
too often to be any good to my students. I had trouble reading.
Grading papers took more energy than I could muster. I had
grown pale and thin and suffered bouts of encephalopathy:
toxins, not processed by my failing liver, lodged in my brain,
resulting in bizarre behavior, like peeing on the floor, and
ambulance trips to the hospital of which I have no memory.
My muscles began to atrophy. I was no longer the mighty force
on my over-40 softball team or a dazzling dinner-and-dance
partner.
I excused myself from a dinner party once to lie down for
a bit. When my friends woke me four hours later, I didn’t
know where I was and barely knew who they were, so they took
me to the hospital, where the doctors gave me some medicine
and asked if I could name the president and my wife’s
birthday. I insisted—wrongly—that her birthday
was the same as mine. But as a way-left liberal, I am obsessed
with George W. Bush, so the president question was a no-brainer
even for a person temporarily deprived of his brain.
For five years, my condition had seemed little more than background
noise. Now it reared up as what it really was: end-stage liver
disease. I experienced nausea, cellulitis (which turned my
lower left leg black), severe fatigue, swollen abdomen, legs
and groin. Not all at the same time, and not in any pattern
I could predict. The only thing predictable about the course
of hep C is that it’s downward.
I figured I was an excellent candidate for a transplant. I
am not a smoker. I had negative colonoscopies and endoscopies.
I breezed through the blood tests, CAT scans, DEXA scans and
echocardiograms. I presented myself to the hospital’s
social worker as an emotionally stable person with a wife
and friends who would provide round-the-clock care for two
to three months after the surgery. And I have insurance: Transplant
surgery costs upward of $350,000. There would be a light at
the end of this very dark tunnel. I was in a hurry to get
to it.
SO IT WAS THAT WARM MORNING IN MAY 2002, standing at the mailbox,
tuna sandwich in one hand, my future clutched in the other.
The letter fairly vibrated in my hand. I opened it slowly
as I made my gimpy way back upstairs to the kitchen. The refrigerator
door stood open and my wife stood over a mound of minced tomatoes.
I read the first line.
“We regret to inform you ... “
I flung the letter at my wife and let out a roar like unto
death itself. I threw the sandwich into the refrigerator as
hard as I could. I wanted—needed—the atavistic
thrill of exploding tuna.
But I was denied even that small satisfaction. The sandwich
shot past the bottles and jars and Tupperware and landed neatly
in its plastic wrap. I should count myself lucky, because
once you start wiping up great wads of tuna salad from the
walls of your refrigerator you might as well clean the whole
dang box. That’s too wretched a task even on the best
day of your life. I wanted to pick up the refrigerator itself
and hurl it out the window. Maybe I could hire three or four
guys from the Millionair Club to heave it through the window
for me. Nothing less would express how rotten I felt. I was
dying of a monster blood virus and I didn’t want anything
but my rightful place in line for some poor, dead guy’s
liver that would otherwise go to waste.
Maybe I should go to Spain where there are no motorcycle-helmet
laws and livers aplenty. The waiting list here is very long.
Whenever a state decides to make motorcycle helmets mandatory,
organ donations plummet. Other things conspiring against me:
a drop in gang violence, lower speed limits in Montana, people
mellowing out through meditation and yoga, automobile air
bags and the Department of Homeland Security.
This kind of thinking leads to madness. Let it go, let it
go. I PICKED UP THE LETTER. It said I was not good transplant
material because, over the course of my life, my use of alcohol
was considered excessive.
What? I hadn’t had a drink in five years. Even in my
younger, wilder days, booze wasn’t a big deal. Sure,
I enjoyed my beer. But beer with pizza after a ballgame isn’t
drinking, it’s a picnic. Wine with dinner? Of course.
But never had a DUI. Never had an accident.
I asked the transplant folks to define “excessive.”
Their answer: Drinking more than one glass of wine a week,
smoking or using any illegal drug was a sign of chemical dependency.
I begged to differ, so I was sent to a specialist who determined
that, in fact, I was not chemically dependent. I now have
an official paper stating that I am not an alcoholic or a
drug addict. Do you? I’m like the guy who gets released
from the mental hospital and is given a paper saying that
he is no longer “mental.” He has proof he’s
not crazy. Do you?
It made no difference to hospital officials. They asked that
I attend Alcoholics Anonymous meetings for six months and
submit to random urine tests to see if I could “handle
this pressure-packed time without resorting to drinking, smoking
or using illicit drugs.” I felt like they were robbing
six months of my life—and daring me to fail.
But they have their rules. And I have this lousy liver. So
I went to AA. It was pretty good. The people I met there were
caring, thoughtful and intensely honest. When I finally gathered
the courage to speak at a meeting, I suggested that part of
the reason we drink is because we are awash in media fairy
tales of relentlessly happy couples sipping cocktails on virgin
beaches or of beautiful women who will be your pal for the
night if you just drink the right beer.
I was shouted down. In AA, there are no excuses. Just tell
your story and sit down.
That’s what I did. And on the day before Thanksgiving
wonder of wonders and hallelujah!—I was welcomed onto
the transplant waiting list.
They gave me a pager. I felt halfway cured.
IT’S BEEN ALMOST A YEAR. There is no way to know when
a liver will show up with my name on it. I need to be good
to go at all times. Think about it: I could be talking on
the phone with my parents in Florida and—beep! beep!—my
pager goes off and life changes forever. They’ll just
have to hold their breath, take a long walk and pray until
the next phone call.
A few hours later, I will emerge with a pre-owned liver and
a regimen of expensive medicine, frequent hospital visits
and unpleasant complications.
Everyone has complications. And I will always have hep C,
but my new liver will buy me some time before it, too, becomes
diseased. The oddsmakers give me an 85 percent chance to make
it a year; 67 percent to make it five years.
But that all presumes I survive surgery.
What if there’s a problem with the anesthesia or an
infection or some simple mistake? Maybe I should write in
permanent marker on my stomach—LIVER RECIPIENT!, along
with my Social Security number and blood type—just in
case.
What if my body rejects the liver? What if people bring me
balloons with Tweety Bird on them?
I had polio when I was 6. We were living in Chicago then,
and I was sent to a hospital for what seemed like months.
I remember thinking the nurse, Miss Tripp, was mean and that
hospitals were such sad places.
They still feel sad to me: the matter-of-fact doctors and
their eager interns; the janitors who scrub the floors and
don’t make eye contact; the guy in the next bed who
watches dopey TV shows; the awkward visits by his relatives
and minister. We, the sick, look at those who are not as if
they won the lottery and we won the wheelchair. Even the floor-moppers
have it better than we do. Oh, to be able to mop the floor.
For months after I got sick, I divided the world into those
who have hep C—namely, me—and the rest of the
world. I felt bitter, alone and alienated from all that is
fun, beautiful and tender. It must be how combat veterans
feel. They know things that they don’t want to talk
about and we don’t really want to know. I live in my
own little combat zone and I am the walking wounded.
It took months before I told more than five or six friends.
This disease is common among drug addicts who use needles.
I could imagine minds at work, speculating, judging. I really
am not certain how I got it. And once you have it, the how
doesn’t much matter. So now I tell everybody. Let them
speculate. Let them judge. As if one dying man is more tragic
than another.
PEOPLE SAY I AM BRAVE, and ask how I manage. I have no good
answer.
I accept that I am living and dying on the edge of limited
time. Aren’t we all? But I have made no pledge forswearing
self-pity, anxiety, anger or depression. Expressions of love
from my wife get me through the hard days. Being sick and
alone has got to be the worst. I urge you to visit, write
a note or make a call to the sick and shut-in. Just to say
hi. Someday you will be grateful for the same.
All my life, I’ve been blessed with a light heart and
a positive attitude. I love James Thurber, P.G. Wodehouse,
Mark Twain and the cartoons in The New Yorker. I love Laurel
and Hardy, Erma Bombeck, Monty Python, Lenny Bruce, Richard
Pryor, Bill Cosby and “Catch-22.” I own a whoopee
cushion, a red nose and a beanie with a bicycle horn glued
on top. I once worked as a street clown with a group called
Free Public Laughs in Chicago.
Every time I laugh, I feel my guts being bathed in milk and
honey and my mother’s chicken soup. Sometimes I’ll
bump into one of my wise-guy friends and he’ll say,
“Hey! You’re not dead yet?” It’s OK.
I laugh. I laugh at this rotten disease and curse it, rip
out its throat and kick it down the stairs. And then I laugh
some more. Laughter is strong and it heals. There is scientific
proof. Read Norman Cousins’ “Head First: The Biology
of Hope and the Healing Power of the Human Spirit.”
Read “Laughter is the Best Medicine” in Reader’s
Digest. Need I say more?
My wife and I are blessed with friends who overwhelm us with
their generosity. They help pay insurance premiums and bring
us homemade meals on wheels. They give us tickets to the opera
and ballgames. Two friends work through our combined Rolodexes
each month, encouraging small gifts of cash and time. Former
students send wall-sized sheets of paper scribbled with good
wishes and poems. One student wrote “To Mr. Slater.
R.I.P.” He wants me to Rest. In Peace. If it sounds
right to him, it sounds right to me.
I was never one to send teddy bears, books or blankets in
the wake of hurricanes, earthquakes or bombings. Bless those
who do. I shall join their ranks. For this is my earthquake.
I must take the pills, exercise, rest, laugh frequently and
start sending those teddy bears, and whatever else the Red
Cross says it needs. LIKE YOU, I’M NOT READY TO DIE.
And this wasn’t supposed to happen to me.
If there was any justice in the world, surviving polio should
have given me a pass on dramatic diseases for the rest of
my life. It left me with a slight limp, but it exempted me
from the draft during the Vietnam War. I’ve lived an
active life but am not a thrill-seeker. A comfortable chair
and a good book are always preferred over activities requiring
helmets, snowshoes or even golf clubs. And in 1997, when I
was 51, I did the right thing and got my over-50 physical.
Two days later, the doctor called to order a follow-up visit.
I imagined a stern talking-to about prostate cancer and cholesterol
levels. Turns out those things were fine. But my blood and
enzyme numbers showed I had end-stage liver disease. Then
the doctor explained what “end-stage” means.
Here I was doing all the right things—teaching school,
building community, staying healthy, getting a physical—and
I get a fetid pie thrown in my face.
I left the office and drove to Alki Beach. It was raining,
and I was grateful for that. A beautiful day would have been
like a slap in the face. I remember the gloriously wretched
smell of low tide. I sucked in the smell of the rotting sea
world. Misery loves wretchedness.
So this is how it’s going to happen for me. A long,
daily death. I’ve had a few friends die of AIDS, a few
of cancer, a couple by suicide and one from hang gliding.
Now it’s my turn?
A SLOW-MOTION DEATH IS NOT HOW I IMAGINED my life would be,
or cease to be. It allows for too much contemplation. I prefer
to “be here now.” Big questions of cosmology and
cosmogony are best left alone. But these days, I can become
obsessed by death. I could die on the surgery slab, an actor’s
last scene in an operating “theater.” Or l could
be one of the 2,500 sick folks who die each year waiting for
a new liver.
And of course there’s still time to be run over by a
truck. At Alki that day, and many times since, I have found
myself confused, sad and defeated, alone with my whoopee cushion
and James Thurber. I imagine conversations that go like this:
Say, Leroy, did you hear that Slater died?
No kiddin’? Man, Slater was a real stand-up guy.
Yes, he was good people. I’ll miss him.
Yeah, me too. Listen, I’m kinda hungry. You wanna get
somethin’ to eat?
Yeah, sure. Let’s go.
That’s how it is and how it’s always been. How
soon they forget. So I imagine my funeral and hope that people
tell the best stories about me and describe me well in all
my complexity. I think the wake should continue for about
a week. If I have any money left, I’ll leave it for
the catering. Lay me in a hammock with my arms folded behind
my head and the ballgame on the radio. Or bury me in a plain
box under some rosebushes to atone for my sometimes lazy approach
to recycling.
My brother says he plans to defy the maxim that says you can’t
take it with you. He wants me to dig a big hole and put him
and all his possessions in together. I will do it for him
if he gets run over by that truck before I do.
I don’t care much about material things. But what about
all my book learning, street smarts, good intentions, the
search for meaning, the love received? It seems like such
a waste to have it thrown in the grave with me. Any love I
have given I know will last forever. There is comfort in that.
Too much time at the office? Not I. I was dancing, singing,
having dinner parties, making art, planting a garden.
So why me? Is there a cosmic reason? Or is it just my time
to get out of the way and free up a parking space?
The answer is there is no answer. Just suffering and, if you
are lucky, meaningful work, good friends, a few opportunities
to love and time to plant tomatoes.
IF I SOUND HOPELESS AND GRIM, keep in mind this is not some
treatable case of prostate cancer. This is me falling down
on the sidewalk and bleeding to death because my blood will
no longer coagulate (highly unlikely except in my overworked
imagination). I look for hope, laughter and love in the neighborhood
of my heart, but I live in the shadow of the valley of death.
I look at my neighbors in Ballard, and they give me joy and
tuna casseroles. About a week after Sept. 11, 2001, I was
scanning the shelves of the Elliott Bay Book Co. Few of the
titles seemed relevant to this new world reality. How could
I buy a book about the Civil War or the flowers of the Sahara?
Here we were, alive in Seattle, trying to understand why some
3,000 of us were dead in New York. A generation of war was
soon to come and attention must be paid. We are on red alert
every day.
In some ways, this world in turmoil has taken the pressure
off me. Now we all have a dis-ease. We are all targeted. Every
lone lunch bucket on the sidewalk warrants a call for the
bomb squad. I feel the same way every time I have a nosebleed.
LAST YEAR, MY DOCTOR TOLD ME I HAD TWO TO THREE YEARS LEFT
to live
with my diseased liver. I said, “WHAT?” He said
three years is a long time. He is from a country where the
average life expectancy is 57 years.
I am 57.
My doctor is a good man and I have come to like him enormously.
I reminded him that in this country, we spend billions on
medical research and have the best of everything at least
those of us with insurance and expect to live very long lives.
I said that in three years, this country will see a whirlwind
of change and I want to be there for it. I want to see if
they discover weapons of mass destruction in Iraq. I want
to see the Mariners win it all someday. I have planted a small
star jasmine whose vine will grow slowly and produce enough
blossoms that will waft sweet springtime delight into our
bedroom. That will take at least six to seven years. The doctor
smiled and said, “I understand. But you have hepatitis
C.”
On the drive home, I threw up. It wouldn’t be the last
time.
Jack Slater is on a medical leave from the Seattle Public
Schools, where he teaches history. He was born in Chicago,
graduated from Calvin College in Michigan and worked for 20
years as an actor and humorist. He has been a community and
political activist and is an avid artist and gardener. He
lives in Ballard with his wife, Deborah Swets, the executive
director of CityClub. You can reach him at jslater@sseattletimes.com
*Seattle Times photographer Alan Berner can be reached at
206-464-8133 or aberner@seattletimes.com
*To reach an editor about this project, contact Jacqui Banaszynski
at 206-464-8212 or jbanaszynski@seattletimes.com
Copyright 2003 The Seattle Times Company
Back to top
October 20, 2003
Massachusetts
Prisons Have High Disease Rate
Massachusetts prisoners have some of the highest rates of
infectious disease in the country, according to a study slated
to be released next week.
Citing a study from the Massachusetts Public Health Association,
The Boston Globe reported that Massachusetts inmates have
the seventh-highest rate of HIV infections in the nation.
And 44 percent of women and 27 percent of men were diagnosed
with Hepatitis C according to the report.
Disease specialists theorized that the higher rate of intravenous
drug use in the Northeast could be part of the cause, the
Globe reported.
Researchers and others have called for health care improvements
for parolees so that they will not infect the communities
they return to after serving their sentences.
Much of the problem is related to substance abuse, Dr. Alfred
DeMaria, the state's director of communicable disease control,
said.
"Substance abuse is clearly the predominant risk factor,"
DeMaria said.
"And if you look at the pattern of imprisonment in this
country over the years, drug crimes are drawing longer and
longer sentences."
Back to top
October 21st, 2003
Schering-Plough
Gets EU Ok For New Pegintron Label
Schering-Plough Corp. said Tuesday that the European drugs
regulator has approved a new label for chronic hepatitis C
treatment PegIntron Injection.
Schering-Plough Europe said that the European Agency for the
Evaluation of Medicinal Products, or EMEA, has approved a
new label for PegIntron (peginterferon alfa-2b) Injection,
the most-prescribed interferon treatment for chronic hepatitis
C.
As noted in the new label, patients are no longer required
to undergo liver biopsy to confirm diagnosis of hepatitis
C and to indicate the potential for treatment impact.
Traditionally, liver biopsy in patients with chronic hepatitis
C has influenced treatment decisions and has been used during
treatment to determine whether the disease has stabilized
or progressed. The revised PegIntron label clarifies for physicians
that a biopsy may not be necessary if a decision to treat
has already been made based on other factors.
For example, the EMEA noted that, since the viral eradication
rate is high (88 percent) for patients with hepatitis C genotype
2/3 virus taking PegIntron and Rebetol (ribavirin) combination
therapy, treatment is often indicated even if the biopsy turns
out to be benign. “Many patients have been put off by
the idea of undergoing an invasive procedure like liver biopsy,”
said Thierry Poynard M.D, Ph.D., Professor of Medicine, Groupe
Hospitalier Pitie-Salpetrier, France. “The new PegIntron
label eliminates a barrier to treating patients at risk for
hepatitis C. This is an important step in fighting this serious
disease.” PegIntron is a longer-acting form of Intron
A (interferon alfa-2b, recombinant) Injection that uses proprietary
PEG technology developed by Enzon, Inc. of Bridgewater, N.J.,
USA.
PegIntron, recombinant interferon alfa-2b linked to a 12,000
dalton polyethylene glycol (PEG) molecule, is a once-weekly
therapy dosed according to patient body weight that is designed
to achieve an effective balance between antiviral activity
and elimination half-life. Schering-Plough holds an exclusive
worldwide license to PegIntron. Rebetol is an oral formulation
of ribavirin, a synthetic nucleoside analog with broad-spectrum
antiviral activity.
It is approved worldwide for use in combination with PegIntron
or Intron A for the treatment of adult patients with chronic
hepatitis C. Schering-Plough has rights to market oral ribavirin
for hepatitis C in all major world markets through a licensing
agreement with ICN Pharmaceuticals Inc. of Costa Mesa, Calif.,
USA.
Chronic hepatitis C is estimated to affect more than 10 million
people in major world markets. In Europe, chronic hepatitis
C is a leading cause of chronic liver disease and one of the
most common reasons for liver transplant.
Schering-Plough Europe, based in Brussels, Belgium, is
a country operation of Schering-Plough Corporation of Kenilworth,
N.J., USA.
Back to top
New Mexico
Inmates to Get Hepatitis Treatment
AP
New Mexico for the first time will began treating prisoners
for hepatitis C, a virus that infects about a third of the
state's 6,200 inmates.
A new generation of medicines that can effectively treat the
virus was not developed until about two years ago, said Dr.
Frank Pullara, medical director for the state Corrections
Department.
Hepatitis C, often contracted through intravenous drug use,
can destroy the liver in a small percentage of those who get
it.
Treatment can range from $15,000 to $30,000 per patient. However,
Pullara said that's only a fraction of the $500,000 price
tag of a liver transplant which the state likely would have
to pay for if an inmate needed it.
"What we want is to catch those people who are going
to have significant damage to their livers if we don't treat
them,'' Pullara said. "If we don't intervene now, sooner
or later, they're going to get into trouble."
A small group of inmates will begin a regimen of pills and
shots, Pullara said.
Four will be undergoing treatment by next week, said Pullara,
a University of New Mexico School of Medicine liver disease
specialist who along with other medical experts developed
a protocol for treating inmates for hepatitis C.
Most people with hepatitis C don't become seriously ill. Pullara
said many with the virus don't even know they have it. There
often are no symptoms. Others feel tired or have mild flu-like
symptoms.
However, 20 percent to 25 percent of those who contract a
chronic infection develop serious complications. They can
develop liver cancer or cirrhosis or their livers ultimately
can stop working.
Pullara said there is no way to tell at the start of the disease
who might develop complications.
Inmates with hepatitis C now have their blood tested periodically
to see whether their liver function is deteriorating.
If a series of those tests reveals an inmate is likely to
suffer liver damage over time, that inmate is referred to
a treatment review committee and their liver functions are
monitored more closely. The committee decides for which inmates
the medication would be appropriate.
Prisoners can decide against treatment. Pullara said side
effects are "horrendous" and include nausea, vomiting
and possibly severe depression.
"If I had 100 people sitting in this room who have hepatitis
C I could only probably convince 10 to take the treatment,"
he said. "This is a fairly brutal treatment."
Back to top
Pamela
Anderson Says Hepatitis C May Kill Her in a Decade
Pamela Anderson says hepatitis C, which she was diagnosed
with in 2001, will probably kill her in a decade.
"I think I've got a good 10 years left in me, which is
sad, too. Maybe 15, if I'm lucky," Anderson tells Us
Weekly magazine in a first-person story for the Nov. 3 issue.
"It's scary, but lately I've been feeling great. For
some reason, my liver keeps getting healthier."
Hepatitis C causes inflammation of the liver, which can lead
to cirrhosis, liver cancer and liver failure. About 3.9 million
Americans have the disease. Anti-viral drugs are a standard
treatment, and therapy is successful about half the time.
But Anderson isn’t taking interferon,
the injectable drug hepatitis patients often use. Her homeopathic
doctor, Wendy Hewland, tells the magazine she "made a
single remedy specifically for Pam" that Anderson is
using as an alternative form of medicine.
The 36-year-old actress, who starred in
the TV shows "Baywatch" and "V.I.P.,"
also says she's no longer planning to marry singer Kid Rock,
to whom she got engaged in April 2002.
"We're not engaged anymore. Our relationship
is not really something you put a label on," she says.
"He wanted to buy me a house in Malibu, Calif., (in August),
but the thing is, I really just need to be with my kids and
work on their relationship with their father."
That would be former Motley Crue drummer Tommy Lee, with whom
she resolved an ugly custody battle in January. The couple
married in 1995 and divorced three tumultuous years later.
"There's definitely a lot of love and history between
Tommy and me, that's for sure. It doesn't matter whether we're
together or not. We're crazy about each other always have
been, always will be,'' Anderson says.
"I'm just happy that my kids (Dylan and Brandon) are
having a healthier, better relationship with their dad. Now
we spend a lot of time together as a family we go to movies,
we cook dinner, everything."
Back to top
Fast-Track
Review Speeds Japan Pegasys Approval
A fast-track review helped Chugai/Roche's Pegasys (recombinant
peg-interferon alfa-2a) gain Japanese approval for chronic
hepatitis C less than a year after filing. The submission
was made in mid-November 2002, resulting in a final clearance
last week. It is the first pegylated interferon approved in
Japan, where around 1.5 million people have chronic hepatitis
C, of whom 30-40,000 are receiving conventional interferon
therapy.
Pegasys's single once-weekly injection regimen (a fixed 180ug
subcutaneously) will considerably simplify treatment, which
should lead to rapid adoption, the firms predict. Local trials
(24 weeks of monotherapy) gave an overall sustained virological
response of 36%, higher than standard interferon, Chugai noted.
90 micro g and 180 micro g injection formulations have been
approved and should be price-listed and launched late this
year, into an interferon market which has grown by 13% on
average over the last four years.
Laboratory
Corporation of America. (LH) To Offer Liver Fibrosis Assay
HCV FibroSure™
PRNewswire
Through Exclusive Relationship With BioPredictive Laboratory
Corporation of America Holdings (LabCorp®) and BioPredictive,
a French diagnostics firm, today announced an exclusive partnership
that combines LabCorp’s expertise in infectious disease
testing with BioPredictive’s noninvasive, predictive
testing technology to quantitatively determine the amount
of liver fibrosis, and the rate of its progression, in hepatitis
C (HCV) patients. HCV FibroSURE™ is expected to be broadly
available in the U.S., only through LabCorp, beginning in
the first quarter of 2004.
This partnership gives U.S. physicians greater options when
assessing their HCV patients for liver fibrosis. As leaders
in their fields, both BioPredictive and LabCorp bring a rare
scientific expertise to the relationship that will benefit
U.S. physicians in search of the most up-to-date and effective
treatment options for HCV.
HCV FibroSURE™ is a noninvasive blood test, which uses
a combination of six serum biochemical markers in a patented
algorithm to predict fibrosis and necroinflammatory activity
in the liver. The extent of fibrosis and necroinflammatory
activity in the liver is a key component of assessing the
need for therapy in HCV infected patients and of predicting
the likelihood of progression to cirrhosis.
The current standard of care for assessing liver fibrosis
and necroinflammatory activity in HCV patients has been a
liver biopsy. However, a liver biopsy is an invasive medical
procedure that carries with it a risk of serious adverse events
due to bleeding and/or other complications.
Using the patented algorithm analysis of results from six
serum biochemical markers, HCV FibroSURE™ has been shown
in several studies to lead to a quantitative and reproducible
assessment of fibrogenic and necrotic activity in the liver
of HCV patients. The blood sample can be readily collected
in minutes and results can be returned to the physician within
days. The innovative, highly sensitive HCV FibroSURE™
assay provides an easily accessible alternative to a liver
biopsy in HCV infected patients.
“The type of scientific and corporate partnership we
have with BioPredictive is a key component of LabCorp’s
strategy to bring the latest in diagnostic technology to the
medical community,” said Myla P. Lai-Goldman, M.D.,
LabCorp executive vice president, chief scientific officer
and medical director. “As the only U.S. clinical laboratory
offering BioPredictive’s groundbreaking technology,
physicians now have additional assessment options for their
HCV patients. We are pleased to add this test to our broad
menu of clinical assays for this disease.”
“When biotechnology companies need a clinical laboratory
partner, they look for a company with a proven business strategy,
as well as scientific and technological expertise,”
said Dr. Thierry Poynard, a world-renowned hepatologist, head
of Hepato-Gastrotroenterology department in Pitie- Salpetriere
Hospital in Paris, researcher and founder of BioPredictive.
“We are excited to be working with LabCorp because they
are leaders in the world of hepatitis testing, and have a
keen understanding of the importance of new technology to
improve the management of HCV patients.”
About BioPredictive
BioPredictive is a young French start-up
of Paris-University, created in 2002, whose main purpose is
studying, designing, and developing biological tests. The
concept is to improve the management of disease by replacing
invasive strategies with noninvasive strategies. The first
step has been the discovery and development of biochemical
markers of chronic liver disease. Fibrotest is a biochemical
marker of liver fibrosis and Actitest is a marker of inflammation
and necrosis of the liver. BioPredictive is the company licensed
by Assistance Public-Hopitaux de Paris (AP-HP) to use and
sell the FibroTest and ActiTest noninvasive tests. These tests
will be available exclusively from LabCorp in the U.S. under
the name HCV FibroSURE™.
One year after FibroTest-ActiTest commercial launch, BioPredictive
performs over 2,000 tests per month and services 150 private
and 12 public hospital laboratories in France, Switzerland,
Portugal, Morocco and Mexico. Our partners are Paris Biotech,
AP-HP, CNRS, Universites Paris 5 and Paris 6. BioPredictive
was rewarded by the French research ministry at the Fourth
National Contest of innovative companies. To learn more about
BioPredictive, visit the web site at: http://www.biopredictive.com/
About LabCorp
Laboratory Corporation of America®
Holdings is a pioneer in commercializing new diagnostic technologies
and the first in its industry to embrace genomic testing.
With annual revenues of $2.5 billion in 2002, over 24,000
employees nationwide, and more than 200,000 clients, LabCorp
offers over 4,000 clinical assays ranging from blood analyses
to HIV and genomic testing. LabCorp combines its expertise
in innovative clinical testing technology with its Centers
of Excellence: The Center for Molecular Biology and Pathology,
in Research Triangle Park, NC; National Genetics Institute,
Inc. in Los Angeles, CA; ViroMed Laboratories, Inc. based
in Minneapolis, MN;
The Center for Esoteric Testing in Burlington, NC; and DIANON
Systems, Inc. based in Stratford, CT. LabCorp clients include
physicians, government agencies, managed care organizations,
hospitals, clinical labs, and pharmaceutical companies. To
learn more about our growing organization, visit our web site
at: http://www.labcorp.com/.
Each of the above forward-looking statements is subject to
change based on various important factors, including without
limitation, competitive actions in the marketplace and adverse
actions of governmental and other third-party payors. Actual
results could differ materially from those suggested by these
forward-looking statements. Further information on potential
factors that could affect LabCorp’s financial results
is included in the Company’s Form 10-K for the year
ended December 31, 2002 and subsequent SEC filings.
Laboratory Corporation of America Holdings
CONTACT: Pamela Sherry of Laboratory Corporation of AmericaHoldings,
+1-336-436-4855, or shareholder direct, +1-800-LAB-0401, orCompany
Information, http://www.labcorp.com/
Web site: http://www.biopredictive.com/
Web site: http://www.labcorp.com/
Back to top
October 22nd, 2003
Schering-Plough
Posts Quarterly Loss, Sales Fall
Bill Berkrot and Ransdell Pierson
Struggling drug maker Schering-Plough Corp. Wednesday reported
a third-quarter loss as sales fell and it increased reserves
for litigation related to investigations into its sales and
marketing practices.
Schering-Plough shares were off nearly 6 percent to near a
seven-year low as it battles a host of problems, especially
evaporation of Claritin sales. The former $3 billion a year
allergy drug went off patent last year and the company began
selling it over-the-counter at a fraction of its former price.
Chief Executive Fred Hassan, hired earlier this year to turn
the company around after bringing Pharmacia Corp. back to
financial health, promised no quick fixes.
“You really need to like both challenges and adventure
to work at Schering-Plough right now,” Hassan said on
a conference call with investors and analysts. “It is
a long process and for many of us it could be a painful process,
but you will see a new Schering-Plough emerge.”
The Kenilworth, New Jersey-based company said it lost $265
million, or 18 cents per share, compared with a profit of
$429 million, or 29 cents, a year ago.
Revenue fell 16 percent to $2.0 billion from $2.4 billion,
reflecting declining sales of its hepatitis C drugs and the
company’s former flagship medicine Claritin.
Excluding the 24 cents a share from the litigation charge,
Schering-Plough earned 6 cents a share—shy of the 10
cents a share Wall Street was expecting.
NO FORECASTS
Hassan declined to provide any future earnings projections,
citing uncertainty over when one of the company’s hepatitis
drugs may face cheaper generic competition and other factors.
“It’s not productive to give lot of numbers which
can be changed overnight,” Hassan said.
The company did provide one number that appeared to unsettle
investors—the addition of $350 million to litigation
reserves for ongoing investigations in Massachusetts and Pennsylvania.
The company said the reserves were an estimate and that actual
legal costs could be less. But it cautioned that costs could
also “materially exceed” the liability reserves
Schering-Plough has set aside.
“We still have a long, hard road ahead on legal front,”
Hassan said.
Meanwhile, sales of the company’s biggest current product
line—its Peg-Intron and ribavirin treatments for hepatitis
C—have plunged following the U.S. launch early this
year of Swiss rival Roche AG’s similar but less-expensive
drugs.
Carrie Cox, the recently appointed president of Schering-Plough’s
global pharmaceutical business, said the company’s former
management was asleep at the wheel as Roche built its presence
in the hepatitis market.
Schering-Plough is now putting much stock in the outcome of
a large clinical trial comparing Peg-Intron with Roche’s
Pegasys drug.
“To do a head-to-head trial clearly indicates our belief
in the superiority of Peg-Intron,” Cox said.
Albert Rauch, an analyst for A.G. Edwards, called the head-to-head
trial a gutsy move, but a gamble borne of desperation.
“Right now their butt is being kicked by Roche,”
he said.
The company’s greatest hope for reviving earnings is
new cholesterol drug Zetia and a pill containing Zetia and
Merck and Co.’s Zocor. The partners later this year
plan to ask U.S. regulators to approve the combination cholesterol
drug.
“Zetia and the Zetia/Zocor combination is the big savior.
That could drive a lot of earnings growth for them,”
said Rauch, who projects $1 billion in Zetia sales next year.
Schering-Plough shares were down 89 cents, or 5.6 percent,
to $15.11 in midday trade on the New York Stock Exchange.
Back to top
Tularik
Receives FDA “Fast-Track” Status
Reuters
Tularik Inc. (TLRK.O: Quote, Profile, Research) on Wednesday
said that the U.S. Food and Drug Administration has granted
it “fast-track” status for T67 for therapy in
patients with unresectable hepatocellular carcinoma, or HCC.
The FDA Fast Track program is used to facilitate the development
and expedite the review of new drugs that are intended to
treat serious or life-threatening conditions.
Amgen Inc. (AMGN.O: Quote, Profile, Research) , the world’s
largest biotechnology company, agreed in May to take a 21
percent stake in Tularik. Tularik, based in South San Francisco,
California, identifies genes associated with cancer.
Back to top
Is Acupuncture
A Risk Factor For Hepatitis?
There is a modest association between hepatitis C and acupuncture,
find investigators in the November issue of the Journal
of Gastroenterology and Hepatology (J Gastroenterol
Hepatol 2003; 18(11): 1231-6).
Acupuncture has been associated with infectious hepatitis.
In this study, investigators from England and the United States
conducted a systematic review to critically evaluate this
risk. The team performed 4 independent literature searches
to identify all epidemiological evidence linking acupuncture
with hepatitis. These studies were validated by the authors
and data extracted according to predefined criteria.
Acupuncture increased the risk of hepatitis modestly
Overall, 15 investigations fulfilled the inclusion criteria.
The majority of these were from Asia. The team found that
5 investigations reported an association between acupuncture
and seropositivity to hepatitis C virus. However, acupuncture
increased the risk of hepatitis modestly. Drs Ernst and Sherman
concluded, “A modest association between hepatitis C
and acupuncture has been reported in some countries”.
“This emphasizes the importance of exclusively using
disposable acupuncture needles”.
Back to top
Health
Officials Report Rise in Hepatitis C
Stephenson County Health Department is watching hepatitis
C rates after noting a rise in cases in 2002. A county health
department annual report showed 17 hepatitis C cases in 2002,
a 40 percent increase over the 12 cases reported in 2001.
But the Illinois Department of Public Health reported 22 cases
of hepatitis C in Stephenson County for 2002. County Health
Administrator Jeff Todd said the discrepancy reflects the
inclusion of later test results and that the IPDH figure is
probably accurate, which means an 80 percent increase in the
number of hepatitis C cases.
The case count represents disease carriers - individuals who
are infected but not symptomatic. From April 2001 - when the
federal government made hepatitis C a reportable disease -
to the present, the state reported 818 infected persons.
Pam Kirkpatrick, communicable disease coordinator for the
Health Department, said doctors are doing a better job of
screening for hepatitis C and advising patients about risk
factors, including having received a blood transfusion or
solid organ transplant before July 1992, having received clotting
factors made before 1987, and having ever been on long-term
kidney dialysis. CDC estimates that injection drug use accounts
for 60 percent of all new cases of the ailment, although body
piercing or tattooing with unsterilized needles, sharing personal
care items, sharing drug paraphernalia and sexual activity
resulting in blood-to-blood contact can also lead to infection.
Antiviral therapy is effective about half the time.
Former “Baywatch” star Pamela
Anderson has hepatitis C. According to news reports today,
she told US magazine in an upcoming issue, “I think
I’ve got a good 10 years left in me, which is sad, too.
Maybe 15, if I’m lucky.” Anderson, who was diagnosed
with the disease in 2001, is currently using homeopathic treatments,
according to reports.
Todd said there are currently about 2 million to 4 million
undiagnosed cases of hepatitis C nationwide.
Back to top
$25 Million
Settlement Offered Over Hepatitis C Outbreak
An outbreak of Hepatitis C at a Norman Regional Hospital pain
clinic has prompted a settlement offer totaling $25 million,
Eyewitness News 5 has learned.
The offer follows the consolidation of dozens of lawsuits
moving through the Cleveland County court system. Among those
named in the litigation: Norman Regional Hospital, Dr. Jerry
Lewis, and nurse anesthetist James Hill.
Hill's role in the transmission of the Hepatitis C virus became
the focus of a state nursing board investigation. He lost
his license earlier this year and was fined $99,000.
Investigators believe Hill reused medical shunts on numerous
occasions, possibly spreading the disease from one patient
to the next.
More than 75 patients were eventually diagnosed with Hepatitis
C, a debilitating inflammation of the liver that can have
lifelong consequences.
The settlement proposal obtained by Eyewitness News 5 would
send a bulk of the payment to those patients who developed
Hepatitis C. 63 individuals would receive $350,000 each. Another
patient, who became ill at an earlier time, would receive
$710,000.
Additional sums would be distributed to those who may have
been at risk, but did not become ill, or who contracted less
serious illnesses. Attorneys would share $670,000 as part
of the settlement, as it is now proposed.
All of the figures are still tentative, according to sources
close to the case, who tell us the $25 million cap is a top
dollar figure.
Parties involved in the lawsuits are unable to comment on
the record because of a confidentiality order issued by the
presiding judge.
Hill has never spoken publicly about the matter. Officials
at Norman Regional Hospital have noted the facility's leadership
role in the investigation and noted Hill was never employed
by the hospital itself, though he did perform contract work
at the clinic.
Dr. Lewis issued a statement last year defending procedures
in place at the clinic and his actions as supervisor of medical
procedures.
Back to top
October 23rd, 2003
Problems
at Schering-Plough Run Deeper Than Hassan Thought
You have to like a challenge and adventure to work at Schering-Plough
at the moment," said the company's CEO, Fred Hassan.
It appears that he has inherited far more problems at Schering-Plough
than he expected.
The troubled company reported a third-quarter net loss of
$265 million compared with profits of $429 million last year
as sales of its key products tumbled in the face of competitor
launches and OTC switches. The loss per share was $0.18 compared
with earnings per share of $0.29 a year ago.
The loss also reflects the addition of $350 million to reserves
to cover pending litigation regarding an investigation into
its past sales, marketing and clinical trial practices. Mr
Hassan, who took control of the company in April, would not
discuss the details of such issues and the outstanding FDA
consent decree during the recent conference call to report
the third-quarter figures.
However, he did acknowledge that he was spending much of his
time with the FDA in a bid to build a level of trust with
the regulatory body that would demonstrate Schering-Plough's
seriousness to resolve the issues.
...product sales
Sales of its once best-selling prescription antihistamine,
Claritin Rx (loratadine), fell by 83% to $68 million, reflecting
the switch of the product to over-the-counter status at the
end of last year. Sales of the company's hepatitis C franchise
of Intron (interferon alfa-2b) products were cut by 43% to
$398 million as Schering-Plough failed to keep up with the
introduction of Roche's competing product, Pegasys (peginterferon
alfa-2a). US Intron sales were hit particularly hard, falling
by 60% to $171 million. The company has now initiated a head-to-head
IDEAL trial to attempt to demonstrate superior efficacy of
its pegylated product, Peg-Intron, over Roche's.
"We continue to see the serious impact of a downward
slope of our key growth drivers and the effect of the severe
challenges and issues should not come as a surprise. We are
working hard to address these but there is no quick fix. It
will be a long and hard process," cautioned Mr Hassan.
Total US pharmaceutical sales fell by 48% to $599 million
during the quarter to result in an overall global pharmaceutical
revenue decline of 24% to $1.6 billion. International pharmaceutical
sales posted a 5% gain to $1 billion but reflected in this
was a favourable foreign exchange rate effect of 9%. Total
global revenues, including animal health and other divisions,
fell by 16% to $2 billion.
Schering-Plough Selected Product Sales ($ mill)
| Product |
3rd qtr |
%chg |
9 mth |
%chg |
| Intron franchise (1) |
398 |
-43 |
1,482 |
-23 |
| Clarinex |
169 |
+3 |
561 |
+33 |
| Remicade |
142 |
+54 |
382 |
+67 |
| Nasonex |
114 |
-29 |
368 |
-8 |
| OTC Claritin |
107 |
n/a |
319 |
n/a |
| Temodar |
90 |
+18 |
237 |
+13 |
| Integrilin |
79 |
+3 |
260 |
+17 |
| Claritin Rx |
68 |
-83 |
289 |
-84 |
| Caelyx |
30 |
+56 |
78 |
+55 |
| Prventil |
23 |
+5 |
82 |
-26 |
(1)includes Intron
A, Peg-Intron and Rebetol.
Since Mr Hassan took control of the company in April, he has
implemented many cost-cutting exercises, but says that the
effects of these will not necessarily filter through to the
bottom line over the coming quarters as the company increases
its investment in sales and marketing activities to stem the
loss of market share for its key products. Selling, general
and administration costs for the quarter were flat at $873
million, while R&D costs rose by 13% to $401 million.
Things at Schering-Plough are not expected to change until
at least 2005, and next year it must contend with the possible
launch of a generic version of its hepatitis C treatment,
Rebetol (ribavirin). Inventories are now being run down ahead
of this scenario, which is further denting sales figures for
the product this year.
...nine months
For the nine-month period, global revenues were down by 17%
to $6.5 billion, with pharmaceutical sales of $5.2 billion,
down by 24%. Net earnings were $90 million, a 95% reduction
over the previous year's figure. EPS were $0.06 compared with
$1.13 in 2002. SCRIP - World Pharmaceutical News FILED 23
October 2003 COPYRIGHT 2003 PJB Publications Ltd
Back to top
EU Removes
Requirement for Liver Biopsy For Pegintron Patients
Reuters
The EMEA has approved new labeling for Schering-Plough's pegylated
interferon product, Pegintron (peginterferon alpha-2b), which
no longer requires that patients undergo a liver biopsy to
confirm their diagnosis. The change is similar to that made
for Roche's rival product, Pegasys (peginterferon alpha-2a),
in July (Scrip No 2869, p 21).
The revised label tells doctors that a biopsy may not be necessary
if a decision to treat has already been made based on other
factors. SCRIP - World Pharmaceutical News FILED 23 October
2003 COPYRIGHT 2003 PJB Publications Ltd
Back to top
Possible
Settlement of Lawsuits Reached in Hepatitis C Outbreak
A proposed $25 million settlement has been reached in more
than 60 civil suits arising from a hepatitis C outbreak at
the Pain Management Clinic of Norman Regional Hospital in
Oklahoma. More than 900 patients treated at the clinic between
May 1999 and August 2002 were tested after a nurse anesthetist
James C. Hill admitted to reusing needles while administering
pain medication. Hill and his supervisor, anesthesiologist
Dr. Jerry W. Lewis, also treated patients at Northwest Surgical
Hospital and the Oklahoma Center for Orthopedic and Multi-Specialty
Hospital, both in Oklahoma City. Tests showed no patient at
those clinics was exposed to hepatitis C.
Liability insurance from all three institutions and the medical
practitioners will be used in the settlement, which may be
approved next week in Cleveland County District Court, Oklahoma
City attorney Glen Huff said Wednesday. Most of the money
will go to 62 patients who have hepatitis C. At a January
meeting, the Oklahoma Board of Nursing revoked Hill’s
license for five years and fined him nearly $100,000. Hill
has admitted he reused needles and syringes but said he did
not think he caused patients any harm. Lewis said he did not
know about Hill’s procedures.
Back to top
October 24th, 2003
Schering-Plough
Provides Grant Supporting Major New Hepatitis C Research And
Education Initiative By American Academy of Family Physicians
Schering-Plough Corporation today announced that it is providing
an unrestricted educational grant in support of a major initiative
by the American Academy of Family Physicians (AAFP) to develop
tools and educational programs concerning hepatitis C for
family physicians.
Hepatitis C is a viral infection of the liver that affects
an estimated 4 million Americans and contributes to approximately
8,000 to 10,000 deaths each year, according to the Centers
for Disease Control and Prevention (CDC). This toll is expected
to triple by the year 2010. Hepatitis C is the most common
cause of chronic liver disease, and associated end-stage liver
disease is the most frequent indication for liver transplantation
among adults. The National Institutes of Health (NIH) estimate
that only about 25 percent of Americans infected with hepatitis
C are aware they have the disease and receive appropriate
treatment.
"Family physicians diagnose more cases of hepatitis C
than physicians in any other specialty," said Michael
Fleming, M.D., president of the AAFP. "Our ultimate goal
is to provide family physicians with resources that will enhance
their efforts to diagnose and effectively treat this disease
and yield the greatest benefits for patients. We appreciate
Schering-Plough's support of this important initiative."
The hepatitis C initiative, part of an AAFP-wide educational
focus on prevention, began with a survey of 1,500 family physicians
concerning their beliefs, knowledge of and clinical practices
related to the screening, diagnosis and treatment of hepatitis
C. The survey included doctors in all 50 states—in rural,
suburban and inner city areas—to better understand their
interactions with hepatitis C patients and to identify barriers
to treatment. The survey findings, which are being processed,
will be used in developing the educational program.
"Schering-Plough is pleased to support the AAFP in this
important effort as part of our continuing role as an industry
leader in providing products and services for the benefit
of people with chronic hepatitis C," said Robert J. Spiegel,
M.D., senior vice president of medical affairs and chief medical
officer, Schering-Plough Research Institute. "As with
any disease, obtaining accurate information about treatment
issues facing hepatitis C patients and their physicians—as
will be identified by the AAFP physician survey—is the
first step in making effective and appropriate treatment more
widely available."
Founded in 1947, the American Academy of Family Physicians
represents more than 94,300 physicians and medical students
nationwide. It is the only medical specialty society devoted
solely to primary care. Please visit
http://www.aafp.org/ for more information about AAFP.
Schering-Plough Research Institute is the pharmaceutical research
and development arm of Schering-Plough Corporation, a research-based
company engaged in the discovery, development, manufacturing
and marketing of pharmaceutical products worldwide.
Back to top
Response
to Standard Hepatitis C Treatment Can Be Predicted As Early
As Week 1
Study of Patients' viral kinetics yields valuable information
for treating physicians
The results of the largest viral kinetics study ever undertaken
in hepatitis C (HCV) patients has found that the sustained
virological response (SVR) to treatment with peginterferon
alfa-2a (40KD)/ribavirin (PEGASYS(r)/ COPEGUS(r)) can now
be predicted as early as week 1 or week 4 - by monitoring
the pattern of how a patient's viral load declines. At the
moment, patients have to undergo 12 weeks of treatment before
finding out if it is likely to be successful.
The DITTO-HCV (Dynamically Individualized Treatment of Hepatitis
C Infection and Correlates of Viral/Host Dynamics) study,
an investigator initiated European Commission project, also
found that although early individualization of treatment according
to viral kinetics could work in principle when more treatment
options are available, it was not possible to improve SVR
rates more than the standard regimen of 24 or 48 weeks of
PEGASYS(r)/ COPEGUS(r) with the treatment modifications that
were tested.
The overall SVR for genotype 1 was 58% for standard treatment
(peginterferon alfa-2a 180 mcg weekly plus 1000 - 1200 mg
ribavirin daily for 48 weeks) versus 49% for individualized
treatment. In genotype 2/3, the SVR was 87% for standard treatment
versus 90% for individualized treatment.
"We discovered that one group of patients that we classified
as 'rapid viral responders' have the best chance of a sustained
virological response with the standard treatment," said
Professor Stefan Zeuzem, Director of the Department of Internal
Medicine at the University Hospital in Homburg, Germany and
DITTO-HCV study investigator. "However, individualized
treatment according to early viral kinetics did not improve
on the sustained virological response that we can already
achieve, since none of the treatment modifications improved
the outcome of the patients that do not have a rapid viral
response."
The conclusion of the study is therefore that the concept
of individualization according to viral kinetics should be
retested when better alternatives exist for those patients
not rapidly responding to the peginterferon alfa-2a/ribavirin
treatment.
Rapid viral responders have most promising results
Rapid viral responders were prospectively defined as patients
whose HCV RNA declined by at least 99% during the first month
of treatment. The study found that in this sub-group, even
the most difficult-to-treat genotype 1 patients could achieve
83% SVR. A relatively high SVR rate (71%) was obtained even
for the rapid responding patients treated with ribavirin for
only the first 6 weeks instead of the standard regimen of
ribavirin during the whole peginterferon treatment of 48 weeks.
These SVR rates are similar to that achieved by genotype 2/3
patients (88%), who traditionally have been easier to treat.
"It is therefore critical for these rapid responding
patients to be identified," said Professor Zeuzem.
New predictive criteria could move the 12 week stopping
rule down to under a month
The DITTO-HCV study retrospectively identified two new criteria
to classify rapid viral responders and predict the likely
treatment outcome. For the DITTO-1st week criterion viral
levels are measured at baseline and two times in the first
week of treatment; while the DITTO-2nd slope criterion uses
three measurements of viral levels between the second and
fourth week of treatment.
"Both of these new criteria predicted who was and who
was not likely to respond to treatment more accurately than
the existing 12-week stopping rule. We had obtained 100% negative
predictive value (NPV) and 90% positive predictive value (PPV)
with these criteria," said Professor Avidan Neumann,
from the Bar-Ilan University, Israel, and the DITTO-HCV study
coordinator.
Using these criteria for stopping treatment in patients predicted
early on not to respond will make treatment more cost-effective,
even considering the added cost of the extra measurements
of viral load.
"This is good news for patients and physicians. Using
these new criteria, we will be able to very early, identify
more of those patients who will ultimately not achieve an
SVR so we can advise them to stop taking their medication,
thus improving their quality of life," said Professor
Neumann.
"We now know that tailoring treatment according to viral
kinetics cannot improve SVR rates with the treatment choices
we have at the moment. However, by measuring viral levels
earlier in treatment, a test physicians are already familiar
with, we can likely move the stopping rule currently defined
at week 12 down to week 4 or even week 1 and avoid having
patients who will not achieve an SVR being treated unnecessarily.
These novel prediction algorithms will hopefully be confirmed
soon by other clinical trials and their feasibility in clinical
practice will be assessed, thus allowing us to optimise the
treatment of hepatitis C patients," concluded Professor
Neumann.
About DITTO-HCV
The DITTO-HCV study is an independent
multi-centre European investigator group initiated study supported
by the European Commission Quality of Life FP5 program (QLK2-2000-00836),
Hoffmann La-Roche and Maxim Pharmaceuticals. 300 patients
with chronic hepatitis C from France, Germany, Greece, Israel,
Italy, Netherlands, Spain, Sweden and Switzerland were enrolled
in the study, which began in April 2001.
Presentation of results
The results of the DITTO-HCV study will be presented at AASLD,
Boston as a poster on Saturday, October 25 and as an oral
presentation on Monday October 27, 2003.
Notes to Editors:
The DITTO trial was conducted through 9 clinical centers in
France (Hopital Mondor, Paris), Germany (Goethe Universitat,
Frankfurt), Greece (Univ. Thessalonoki), Israel (Tel-Aviv
Sourasky Medical Center), Italy (University Hospital of Parma),
Netherlands (Erasmus Univ Hospital Rotterdam Dijzit), Spain
(Univ. Barcelona), Sweden (Goeteborg Univ.) and Switzerland
(Univ. Geneve) and coordinated in Israel (Bar-Ilan University).
References:
*Neumann AU, Schalm SW, von Wagner M, Germanidis G, Lurie
Y, Missale G, Martell M, Vrolijk J-M, Norkrans G, Soulier
A, Verheij-Hart E, Colucci G, Ferrari C, Zeuzem S & Pawlotsky
J-M. Early viral kinetics prediction of sustained virological
response after 1 or 4 weeks of peg-interferon-alfa-2a and
ribavirin therapy (DITTO-HCV Project). Presented at the American
Association for the Study of Liver Diseases, Boston, October
24-28 2003. Abstract no. 192. Hepatology, October,
2003, Vol. 37, No. 4, Suppl. 1, 248A.
*Zeuzem S, Pawlotsky J-M, Hagai E, von Wagner M, Goulis I,
Lurie Y, Gianfranco E, Vrolijk J-M, Esteban JI, Soulier A,
Verheij-Hart E, Hansen B, Tal R, Ferrari C, Schalm SW &
Neumann AU. International, multicenter, randomized, controlled
study comparing standard versus dynamically individualized
treatment in patients with chronic hepatitis C (DITTO-HCV
Project). Presented at the American Association for the Study
of Liver Diseases, Boston, October 24-28 2003. Abstract no.
317. Hepatology, October, 2003, Vol. 37, No. 4, Suppl.
1, 310A.
For more information please contact: Prof. Avidan U Neumann,
+972-58-808-626
Back to top
Schering-Plough
Reports Novel Investigational Protease Inhibitor
Schering-Plough Corporation (NYSE: SGP) today reported that
a novel investigational protease inhibitor developed by Schering-Plough
Research Institute (SPRI) was shown to be a potent inhibitor
of hepatitis C virus (HCV) replication in vitro, according
to data provided by researchers in an oral presentation(1)
here today at the 54th annual meeting of the American Association
for the Study of Liver Diseases (AASLD).
The hepatitis C protease is a viral enzyme complex that is
essential to the replication of the hepatitis C virus. By
interfering with viral replication, HCV protease inhibitors
may represent a new antiviral approach to treating hepatitis
C patients.
"The development of protease inhibitors has been a major
milestone in the treatment of HIV infection. Now companies
such as Schering-Plough are beginning to test the first of
similar drugs to treat the hepatitis C virus, which can cause
fatal liver disease and has infected millions of people worldwide,"
said Francesco Negro, M.D., divisions of gastroenterology
and hepatology, and of clinical pathology, University Hospital,
Geneva, Switzerland, who presented the data. "Hepatitis
C protease inhibitors have the potential to have the same
impact on HCV therapy that the HIV drugs have had," he
said.
"These encouraging findings suggest this class of drugs
is a promising area of research in the treatment of hepatitis
C," said Cecil B. Pickett, Ph.D., president of Schering-Plough
Research Institute. "Once developed, these protease inhibitors,
either alone or in combination with existing therapies, may
help in eradicating the hepatitis C virus in patients chronically
infected with the disease. Our lead compound in this area
has just begun clinical testing."
Schering-Plough has a dedicated HCV protease inhibitor development
program. Its researchers, leaders in the structural biology
of HCV, are using their expertise to design potent antiviral
agents that can inhibit the enzyme activities required for
HCV maturation and replication. As the worldwide leader in
developing new and more effective treatments for hepatitis
C, Schering-Plough is well positioned to develop and market
innovative therapies that target HCV replication. The company
in 1991 introduced the first product approved in the United
States for treating chronic hepatitis C and in 1998 launched
the first combination therapy. In 2001, Schering-Plough introduced
the first pegylated interferon therapy. Today, PEG-INTRON(R)
(peginterferon alfa-2b) Powder for Injection in combination
with REBETOL(R) (ribavirin, USP) Capsules is the most prescribed
treatment for hepatitis C worldwide. More than 300,000 hepatitis
C patients worldwide, including 175,000 U.S. patients, have
received this combination therapy since its introduction in
2001.
Study Results
Dr. Negro, along with fellow scientists from University Hospital
and working with a team of SPRI researchers, used multiple
procedures to assess the antiviral activity of a novel protease
inhibitor in the Schering-Plough portfolio known as SCH6 in
a standard cell line (Huh-7 hepatoma cells) that was infected
with HCV. After a 72-hour incubation period with varying concentrations
of SCH6, viral transcription and protein expression were measured
by real-time polymerase chain reaction, or PCR (by TaqMan),
quantitative in situ hybridization, immunoblot and indirect
immunofluorescence.
HCV replication and expression were effectively inhibited
by SCH6, which reached its peak activity at 100 nM, as consistently
shown by all procedures used. At these concentrations and
for these lengths of incubation, SCH6 did not appear to induce
cytotoxic morphological changes or apoptosis (cell death).
Researchers noted that while HCV protease inhibitors show
promise in early stage development, much additional work will
be required before this class of compounds becomes available
to patients.
Schering-Plough Commitment to Hepatitis C As the leading innovator
of interferon-based treatments for hepatitis C, Schering-Plough
on Sept. 23, 2003, announced plans to initiate the IDEAL trial,
a major clinical study involving 2,880 patients that for the
first time will directly compare the two approved forms of
pegylated interferon therapy for chronic hepatitis C: PEG-INTRON
versus PEGASYS (peginterferon alfa- 2a/Hoffmann-La Roche,
Inc.), both used in combination with ribavirin. Schering-Plough
Research Institute, in collaboration with leading medical
centers, will conduct the comparative study in response to
requests by the hepatitis C medical and patient communities,
and to clear up misperceptions in the marketplace about these
two treatments.
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Researchers
Identify Essential Component of Immunity against the Hepatitis
C Virus
Researchers at Columbus Children's Research Institute (CCRI)
on the campus of Columbus Children's Hospital have identified
a key component of protective immunity against the hepatitis
C virus, the major cause of chronic liver disease and transplantation
in the United States. The study found that successful control
of hepatitis C infection required close cooperation between
two types of white blood cells know as CD4+ "helper"
and CD8+ "killer" T lymphocytes. The findings, published
in the October 24 issue of Science, indicate that
the immune system is unable to eliminate the virus without
the CD4+ T lymphocytes.
"Our goal is to understand how a person's immune response
determines the outcome of the hepatitis C infection,"
said Christopher M. Walker, Ph.D., director of the Center
for Vaccines and Immunity at CCRI on the campus of Columbus
Children's Hospital and professor of pediatrics at The Ohio
State University College of Medicine and Public Health. "Approximately
70 percent of individuals exposed to hepatitis C become lifelong
carriers of the virus. The remaining individuals successfully
contain the infection and appear to have long-lasting immunity
to the virus. Our finding that CD4+ T helper cells are essential
for this protection move us one step closer to developing
an effective vaccine for hepatitis C," he added.
There are 170 million people around the world (including 4
million in the United States) infected with the hepatitis
C virus. Most of these people don't know they are chronic
carriers of the virus until they develop liver problems.
The study, conducted in an animal model of human hepatitis
C infection, demonstrated that temporary depletion of the
CD4+ T helper cells abolished protective immunity against
a second infection with the virus. The CD8+ T killer lymphocytes
alone were an ineffective defense as the virus rapidly mutated
to evade this immune response.
"Vaccines are the most cost-effective way to contain
viruses like hepatitis C and with these findings, we move
one step closer to that goal," added Dr. Walker.
Columbus Children's Hospital ranks among the top 10 in National
Institutes of Health research awards and grants to freestanding
children's hospitals in the country. With nearly 500,000 patient
visits each year, Children's Hospital is a 111-year-old pediatric
healthcare network treating newborns through age 21. In 2002,
the Children's Research Institute conducted more than 250
research projects and is the home of the Center for Injury
Research and Policy along with other Centers of Emphasis encompassing
gene therapy; molecular and human genetics; vaccines and immunity;
childhood cancer; cell and vascular biology; developmental
pharmacology and toxicology; and biopathology. Pediatric Clinical
Trials International (PCTI), a site management organization
affiliated with the hospital, also coordinated more than 50
clinical trials. In addition to having one of the largest
ambulatory programs in the country, Children's offers specialty
programs and services. Each year, more than 75,000 consumers
receive health and wellness education, and 2,000 students
from 93 institutions and 500 residents receive training at
Children's. More information on Children's Hospital of Columbus
is available by calling (614) 722-KIDS (5437), or through
the hospital's Web site at
http://www.columbuschildrens.com.
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October 25th, 2003
New Drug
Hope for Millions of Hepatitis C Victims
A new drug that prevents a contagious virus from duplicating
in the body could be a new weapon against hepatitis C, a disease
that could kill more people than AIDS, scientists said.
More than 170 million people around the globe are infected
with the virus that can cause permanent liver damage and in
many cases death.
There is no vaccine against the hepatitis C virus (HVC) and
current treatments can cause unwanted side effects.
But scientists working for the German drugs giant Boehringer
Ingelheim have developed a drug that could offer new hope
to patients with the illness.
Called BILN 2061, the drug targets an enzyme to block the
replication of the virus.
In eight people given four doses of the treatment viral loads,
or the amount of virus in the blood, dropped by 100 to 1,000
fold after 48 hours without producing any unpleasant reactions
in the patients.
"The antiviral results of protease inhibitor BILN 2061
in a proof-of-concept human trial clearly demonstrate the
great potential of selective and anti-HCV agents," Daniel
Lamarre, of the company research centre in Laval, Canada,
said in a report published online by the science journal Nature.
BILN 2061 is the first of a class of drugs called NS3 protease
inhibitors to be tested in humans.
Although more longer trials are needed to see if the drug
keep the viral load down and if resistance develops, the scientists
believe it "holds great promise to markedly improve treatments
of chronic HCV infection."
Former US surgeon general Dr C Everett Koop has described
the illness as a graver threat to public health than AIDS.
"Hepatitis C already infects three times more people
than does AIDS. It is responsible for more than one-third
of all liver transplants," Dr Koop warned in an Internet
message, adding that the illness could kill more people than
AIDS each year.
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October 27th, 2003
Shorter
Interferon/Ribavirin Course Effective for Chronic Hepatitis
C Types 2 & 3
by Peggy Peck
Among patients with chronic hepatitis C (HCV) genotype 2 or
3 infection, 24 weeks of PEG-interferon alfa-2b plus ribavirin
treatment is as effective as a 48-week regimen, according
to results of a study of presented at the 54th Annual Meeting
of the American Association for the Study of Liver Diseases.
The shorter course has the added bonuses of lower cost and
fewer side effects.
"Look at the response rates: 81% of patients achieved
sustained viral response with just 24 weeks of treatment,"
said principle investigator Dr. Stefan Zeuzem of Saarland
University Hospital, Homburg, Germany.
Two hundred twenty-four HCV patients (42 genotype 2, 182 genotype
3) were enrolled in the study in which they were treated with
PEG-interferon alfa-2B 1.5g/kg plus ribavirin 800-1000 mg/day.
The results were compared with those achieved in historical
controls treated with the same combination for 48 weeks.
In an interview with Reuters Health, Dr. Zeuzem said that
HCV treatment is often compromised by "the side-effects
that cause patients to reduce dose or discontinue therapy.
But if you look at the historical data from studies of 48
weeks, what we see is a response at 24 weeks and then the
side effects become evident during the second half of treatment.
By shortening treatment, we are significantly reducing the
depression, fatigue, headaches—the side effects that
make the treatment so difficult."
The end-of-treatment response rate with the shortened course
was 94% (versus 95% among historical controls), and the estimated
sustained virologic response rate at 48 weeks was 84%.
Dr. Zeuzem also pointed out that "standard 48-week treatment
costs about 20,000 euros, so 24-weeks costs about 10,000 euros."
He predicted similar reductions in cost in the U.S.
"Twenty-four weeks should now be considered the standard
for patients with genotype 2 and 3," he said.
Dr. Zeuzem noted that the shortened treatment regimen is much
better tolerated by patients as evidenced by improved compliance:
only 5% of patients discontinued treatment, while the discontinuation
rate in historical controls is 14%. Likewise, 22% of patients
required dose reduction during the 24 weeks, while doses were
reduced in 49% of historical controls.
The study was funded by Schering-Plough Research Institute,
Kenilworth, NJ.
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Study Shows
24 Weeks of Pegintron Combination Therapy As Effective As
48 Weeks In Genotype 2/3 Hepatitis C Patients
Results of study conducted as a post-approval commitment to
EMEA reported at 54th annual AASLD meeting in USA
Study of PegIntron individualized, weight-based therapy in
difficult-to-treat genotype 4 virus also reported at AASLD
Schering-Plough Europe today reported results of a clinical
study demonstrating that a 24-week course of individualised,
weight-based PegIntron(R) (peginterferon alfa-2b) Powder for
Injection and Rebetol(R) (ribavirin) Capsules is as effective
as a 48-week course (historical control data) in achieving
sustained virologic response (SVR) in patients infected with
hepatitis C virus (HCV) genotypes 2 and 3, with the shorter
treatment regimen being better tolerated by patients(1). SVR
is defined as the sustained undetectability of HCV six months
following the end of treatment and is the standard criterion
for efficacy. Results of the study were reported as a "late-breaker"
poster presentation at the 54th annual meeting of the American
Association for the Study of Liver Diseases (AASLD) in Boston,
Mass., USA.
Investigators also reported results of clinical studies involving
a broad range of hepatitis C patients, which confirmed that
individualised, weight-based dosing of PegIntron in combination
with Rebetol is effective in treating chronic infections with
various forms of the hepatitis C virus, including genotypes
2, 3 and 4. In all, there were 54 PegIntron study abstracts
presented at the AASLD meeting.
Shorter Treatment Duration in HCV
Genotypes 2, 3
In this study, the safety and efficacy of a 24-week course
of therapy with PegIntron (1.5 ug/kg/wk) and Rebetol (800-1,400
mg/day) in 224 previously untreated patients with hepatitis
C genotype 2 or 3 were compared to historic controls from
a previous study of the same therapy for 48 weeks(2). Results
showed that 81 percent of patients overall (93 percent for
genotype 2 and 79 percent for genotype 3) achieved a sustained
virologic response, which was statistically equivalent to
the SVR rates seen in the 48-week study. SVR did not vary
with patient body weight, supporting the efficacy of weight-based
dosing.
Additionally, patients who adhered to the 24-week treatment
regimen—defined as taking at least 80 percent of their
medication for at least 80 percent of the 24-week treatment
period—achieved an even higher SVR rate of 86 percent
overall (97 percent for genotype 2 and 84 percent for genotype
3).
Importantly, the 24-week treatment regimen resulted in only
5 percent of patients withdrawing from the study and only
22 percent requiring dose reductions, compared to 14 percent
and 49 percent, respectively, for patients in the 48-week
study. Less than 1 percent of patients reported serious adverse
events for depression or neutropenia with the shorter course
of treatment.
"These are clinically important findings in that treatment
with 24 weeks of PegIntron and Rebetol in patients with HCV
genotypes 2 or 3 had similar efficacy but, due to the shorter
duration, fewer patient withdrawals or dose reductions compared
to a historical control using the current standard treatment
regimen," said Professor Stefan Zeuzem, M.D., Saarland
University, Homburg, Germany. "Patients found the 24-week
treatment regimen easier to tolerate," he said.
Schering-Plough said that it will provide data from this study
to regulatory authorities in the European Union in response
to a post-approval commitment and expects to file a marketing
application for the 24-week regimen with the EU's Committee
for Proprietary Medicinal Products (CPMP).
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Efficacy
in HCV Genotype 4: Unmet Need
In another key study presented at AASLD, individualised, weight-based
PegIntron and Rebetol combination therapy was shown to be
effective in previously untreated patients infected with HCV
genotype 4,(3) which is the predominant form of hepatitis
C in the Middle East. Genotype 4 virus has not been widely
studied to date, but is known to be difficult to treat successfully.
Lead investigator Fuad Hasan, M.D., department of medicine,
Kuwait University, presented results of this open-label, prospective
study of 48 weeks of PegIntron (1.5 ug/kg/wk) and Rebetol
(1,000-1,200 mg/day) combination therapy in 44 previously
untreated patients infected with HCV genotype 4. Of these
patients, 30 percent had advanced disease as indicated by
liver cirrhosis, which is known to make successful treatment
more difficult.
Results of the study showed that 61 percent of patients achieved
an SVR. The data also showed a low relapse rate of only 7
percent, an important finding in this hard-to-treat patient
population. Relapse is defined as the recurrence of HCV infection
during the six-month follow-up period in a patient who achieved
an end-of-treatment response. Treatment was well tolerated
by most patients.
"These findings with weight-based PegIntron and Rebetol
combination therapy are very encouraging, especially given
that genotype 4 is generally known to be difficult to treat,"
said Hasan. "To date, most therapeutic trials have enrolled
patients infected with HCV genotypes 1, 2 or 3. Data regarding
the responsiveness of genotype 4 is very limited and further
study is warranted," he said.
"The results of these studies and the other research
findings presented at the AASLD meeting bear out our confidence
in the broad, proven efficacy of individualised, weight-based
dosing of PegIntron in combination with Rebetol in treating
hepatitis C worldwide," said Robert J. Spiegel, M.D.,
senior vice president of medical affairs and chief medical
officer, Schering-Plough Research Institute.
"As the leading innovator of interferon-based treatments
for hepatitis C, Schering-Plough is committed to conducting
and supporting research to address scientifically the effective
and safe treatment of patients with hepatitis C," Spiegel
said. "We are confident that the numerous ongoing clinical
studies with PegIntron and Rebetol combination therapy will
provide valuable information that will help physicians make
informed choices and provide hepatitis C patients with the
best chance for achieving a sustained viral response."
PegIntron and Rebetol
PegIntron and Rebetol combination therapy is the most prescribed
treatment for hepatitis C worldwide. More than 300,000 hepatitis
C patients worldwide, including 175,000 U.S. patients, have
received this combination therapy since its introduction in
2001.
PegIntron is a longer-acting form of Intron(R) A (interferon
alfa-2b, recombinant) Injection that uses proprietary PEG
technology developed by Enzon, Inc. of Bridgewater, N.J.,
USA. PegIntron, recombinant interferon alfa-2b linked to a
12,000 dalton polyethylene glycol (PEG) molecule, is a once-weekly
therapy dosed according to patient body weight that is designed
to achieve an effective balance between antiviral activity
and elimination half-life. Schering-Plough holds an exclusive
worldwide license to PegIntron.
Rebetol is an oral formulation of ribavirin, a synthetic nucleoside
analogue with broad-spectrum antiviral activity. It is approved
worldwide for use in combination with PegIntron or Intron
A for the treatment of adult patients with chronic hepatitis
C. Schering-Plough has rights to market oral ribavirin for
hepatitis C in all major world markets through a licensing
agreement with ICN Pharmaceuticals Inc. of Costa Mesa, Calif.,
USA.
Chronic hepatitis C is estimated to affect more than 10 million
people in major world markets. In Europe, chronic hepatitis
C is a leading cause of chronic liver disease and one of the
most common reasons for liver transplant.
Back to top
Roche Study
May Bring Wider Use of Pegasys Hepatitis C Drug
Kim Frick
Roche Holding AG's Pegasys drug can help patients fight the
potentially fatal liver disease hepatitis C, even those with
normal enzyme levels who don't usually receive treatment,
a study showed.
Levels of the enzyme alanine aminotransferase or ALT have
been widely used to identify patients with liver injury and
liver disease for the last 50 years, Basel, Switzerland-based
Roche said in an e-emailed release. Only patients with elevated
or abnormal ALT levels in their blood are usually treated.
The study of 514 patients showed that one quarter to one third
of all patients in the test had some degree of fibrosis or
liver inflammation, even with normal ALT readings, and responded
to Pegasys. The results were released at the American Association
for the Study of Liver Diseases in Boston. Researchers said
ALT is not a good indicator for liver disease and shouldn't
be used in isolation.
“Patients with normal ALT levels were often considered
to have mild hepatitis and could, therefore, wait for treatment,
said Stefan Zeuzem, lead investor in the study and director
of the department of internal medicine at the University Hospital
in Homburg, Germany. The results “challenge the old
beliefs and show that normal ALT levels do not accurately
reflect the condition of the patient's liver.''
The data may help the Swiss drugmaker boost sales of Pegasys
which rose to 619 million Swiss francs ($470 million) in the
first nine months of this year. Roche Chief Executive Officer
has said he expects Pegasys to grab 50 percent of new prescriptions
in the first quarter of next year.
“A trial showing the value of Pegasys in patients with
normal ALT levels could significantly boost demand,'' Denise
Anderson, a pharmaceutical analyst at Julius Baer Brokerage,
wrote in a note to investors.
Humer has said Pegasys, which won U.S. approval in December
and competes with Schering-Plough Corp.'s Peg-Intron, may
generate peak annual sales of 2 billion francs. Roche expects
to outpace the industry average for drug sales growth this
year with new medicines such as Pegasys.
Back to top
New Study
Investigates Pegasys and Copegus for the Treatment Of Chronic
Hepatitis C in African Americans
Important news for African Americans- Historically one of
the most difficult to treat hepatitis C patient populations
-
New data on response to treatment in African Americans with
chronic hepatitis C using the combination of Pegasys (peginterferon
alfa-2a) and Copegus (ribavirin, USP) were reported on Sunday,
October 26, at the American Association for the Study of Liver
Diseases (AASLD) 54th annual meeting in Boston, MA.
This is the largest prospective study reporting the efficacy,
safety and tolerability of pegylated interferon and ribavirin
combination therapy in non-Hispanic African Americans compared
to Caucasians, all of whom had genotype 1 hepatitis C, the
most difficult to treat.
In this study, the combination therapy of Pegasys and Copegus
yielded a 26 percent sustained virological response (SVR)
in African American patients. The sustained virological response
rate for Caucasian patients in the study was 39 percent. Sustained
virological response refers to a patient's continued undetectable
serum hepatitis C RNA levels 24 weeks after finishing a course
of treatment.
“These data are especially important because African
Americans have historically been underrepresented in clinical
trials for hepatitis C,” said Juan Carlos Lopez-Talavera,
MD, PhD, Medical Director, Roche Laboratories, Inc. “With
these data, we can better understand how best to manage this
large and difficult to treat patient population.” Pegasys,
a pegylated alpha interferon, and Copegus, an oral antiviral,
were approved by the FDA in December 2002 for use in combination
for the treatment of adults with chronic hepatitis C who have
compensated liver disease and have not previously been treated
with interferon alpha. Patients in whom efficacy was demonstrated
included patients with compensated liver disease and histological
evidence of cirrhosis.
Study Design
The study was conducted at eleven sites in the United States
and included 78 African American patients and 28 Caucasian
patients. All patients were interferon-naove with chronic
hepatitis C genotype 1 and elevated ALT levels. Patients received
180 mcg subcutaneously of Pegasys, once weekly, along with
either 1000 or 1200 mg/day of Copegus, depending on their
weight, for 48 weeks, with 24 weeks of treatment-free follow-up.
Early virological response (EVR) was assessed at 12 weeks
of therapy and SVR at week 72.
This trial included a relatively small cohort of patients
receiving treatment. Studies with larger patient populations
are currently underway to confirm the findings from this study.
Conclusions should not be drawn in non-African American populations
because of the small numbers (n=28) of non-African Americans
in the study.
Adverse Events
Adverse events were similar to those seen in Pegasys and Copegus
registration trials. Incidence rates for AEs among the Caucasian
patient and African American patient groups included: fatigue
(71 percent vs. 60 percent), headache (82 percent vs. 54 percent),
insomnia (50 percent vs. 27 percent), and nausea (54 vs. 23
percent). Five percent of African American patients and fourteen
percent of Caucasian patients withdrew prematurely due to
adverse events or laboratory abnormalities. African Americans
had lower baseline absolute neutrophil counts compared to
Caucasian patients. Dose modifications of Pegasys (withheld
or reduced) occurred among 46 percent of African Americans
and 29 percent of Caucasians; the most common cause was neutropenia
(37 percent among African Americans and 18 percent among Caucasians).
The Impact of Hepatitis C on African Americans
African Americans have the highest prevalence rates for hepatitis
C among all racial and ethnic groups in the United States,
but have historically been underrepresented in clinical trials
examining the treatment of the disease. Almost all African
Americans with hepatitis C are infected with genotype 1 (91
percent compared to 67 percent of Caucasians with hepatitis
C). Hepatitis C is a blood-borne virus that chronically infects
an estimated 2.7 million Americans. It can cause progressive
liver injury and lead to fibrosis and eventually cirrhosis.
About Pegasys
Roche has backed Pegasys with the most extensive development
program ever undertaken in hepatitis C, including major studies
initiated to advance treatment for hepatitis C patients with
unmet needs, including African Americans, patients co-infected
with HIV and HCV, patients with cirrhosis, patients with normal
ALT levels, and patients who have failed to respond to previous
therapy.
Roche also has taken a leading role in reducing the cost of
hepatitis C therapy by conducting a landmark study that reduced
the duration of therapy for certain patients and by pricing
Copegus, at its introduction in January 2003, at a wholesale
acquisition cost or list price that was 43 percent less per
milligram than the other available brand of ribavirin.
About Roche
Hoffmann-La Roche Inc. (Roche), based
in Nutley, N.J., is the U.S. prescription drug unit of the
Roche Group, a leading research-based health care enterprise
that ranks among the world's leaders in pharmaceuticals, diagnostics
and vitamins. Roche discovers, develops, manufactures and
markets numerous important prescription drugs that enhance
people's health, well-being and quality of life. Among the
company's areas of therapeutic interest are: dermatology;
genitourinary disease; infectious diseases, including influenza;
inflammation, including arthritis and osteoporosis; metabolic
diseases, including obesity and diabetes; neurology; oncology;
transplantation; vascular diseases; and virology, including
HIV/AIDS and hepatitis C. For more information on the Roche
pharmaceuticals business in the United States, visit the company's
web site at: http://www.rocheusa.com
Facts About Pegasys (Peginterferon alfa-2a) in Combination
with Copegus
Indication
Pegasys., a pegylated alpha interferon, alone or in combination
with Copegus. (ribavirin, USP) is indicated for the treatment
of adults with chronic hepatitis C who have compensated liver
disease and have not previously been treated with interferon
alpha.
Patients in whom efficacy was demonstrated included patients
with compensated liver disease and histological evidence of
cirrhosis (Child-Pugh class A).
Dosing and Administration
Pegasys, a premixed solution, is dosed at 180mcg as a subcutaneous
injection once a week. Copegus, available as a 200mg tablet,
is administered at 800 to 1200mg taken twice daily as a split
dose.
The two products are sold separately.
Combination Therapy Clinical Studies
The two combination therapy pivotal study findings:
Study 5, including 1,284 patients receiving medication, showed
that patients with certain genotypes (strains) of the hepatitis
C virus should be treated with different dosing regimens of
Pegasys and Copegus. The treatment regimens and resulting
sustained virological response rates for these groups treated
with Pegasys and Copegus therapy were: Genotype 1: 48 week
duration with 1000 - 1200mg Copegus: 51 percent Genotype non-1:
24 week duration with 800mg Copegus: 82 percent.
Study 4, published in the September 26, 2002 New England
Journal of Medicine, including 1,121 patients receiving
medication, showed that Pegasys and Copegus combination therapy
is a more effective treatment for chronic hepatitis C than
interferon alfa-2b and ribavirin. The sustained virological
response rate in the Pegasys and Copegus treated patients
was 53 percent compared to 44 percent in the interferon alfa-2b
and ribavirin group. Sustained virological response refers
to a patient's continued undetectable serum hepatitis C RNA
levels 24 weeks after finishing a course of treatment.
The Future - Special Populations, HIV/HCV Co-infection
Pegasys and Copegus studies are underway to evaluate the therapy
for the treatment of African-Americans, who have a substantially
higher prevalence of hepatitis C infection and typically have
lower response rates to hepatitis C therapy than Caucasian
Americans.
Trials also are being conducted to evaluate Pegasys and Copegus
treatment in patients co-infected with hepatitis C and HIV
and in patients with hepatitis C who failed to achieve a sustained
virological response to standard interferon and ribavirin.
Back to top
New Study
Demonstrates Benefits of Hepatitis C Therapy among Previously
Under-Treated Patient Population
New research from the Virginia Commonwealth University Medical
Center and other institutions demonstrates hepatitis C patients
with normal alanine aminotransferase (ALT) levels benefit
from treatment with a combination therapy of Pegasys. (peginterferon
alfa-2a) and Copegus. (ribavirin, USP). Results from this
first, international, large-scale study to investigate the
use of pegylated interferon in patients with normal ALT levels
were presented today at the American Association for the Study
of Liver Diseases (AASLD) annual meeting in Boston, Mass.
"These findings suggest that a large number of hepatitis
C patients with normal ALT levels would benefit from Pegasys
combination therapy," said Mitchell L. Shiffman, M.D.,
chief of the Hepatology Section and medical director of VCU's
Liver Transplant Program, who was a U.S. investigator on the
study. "While normally associated with milder liver disease,
ALT levels vary from person to person and can fluctuate from
month to month. This study provides a great deal more information
on how we should treat the 30 percent of chronic hepatitis
C patients who have normal ALT levels."
ALT is an enzyme that is released by the liver when it becomes
damaged and levels of ALT tend to increase with the degree
of liver injury. However, once cirrhosis occurs, levels may
or may not be high. Because of a lack of data, there has been
no consensus on whether or not patients with chronic hepatitis
C and normal ALT levels should receive treatment.
In this study, 30 percent of patients treated for 24 weeks
and 52 percent of patients treated for 48 weeks achieved a
sustained virologic response (SVR). Sustained virologic response
refers to patients in whom the hepatitis C virus remains undetectable
24 weeks after finishing a course of treatment. According
to Shiffman, patients with SVR rarely develop recurrent hepatitis
C.
For patients with genotype 1, the most difficult to treat
strain of the virus and the most common in the United States,
40 percent of patients treated for 48 weeks achieved a SVR.
In those patients with genotype 2 or 3 treated for 24 weeks,
response rates reached nearly 80 percent. These response rates
are similar to those seen in previous Pegasys combination
therapy studies conducted in patients with elevated ALT levels.
Recommendations suggest that genotype 1 patients with elevated
ALT be treated with 1000-1200 mg of ribavirin. Patients in
this study were treated with 800 mg suggesting that those
with normal ALT can be just as successful on treatment with
lower doses of ribavirin. Additionally, patients in the control
arm that had normal ALT and were not treated did have significant
liver disease progression. Data on adverse events was similar
to previous studies of pegylated interferon for the treatment
of chronic hepatitis C. However, the incidence of the most
common adverse events associated with pegylated interferon
was lower in patients with normal ALT levels compared to the
incidence observed in patients with abnormal or high ALT levels
in other studies of Pegasys and Copegus.
The study included 491 patients worldwide that were randomized
to three treatment arms: 212 were treated with Pegasys 180
mcg/week and Copegus 800 mg/day for 24 weeks; 210 received
the same combination for 48 weeks and 69 patients received
no treatment. All patients were monitored for 72 weeks.
Hepatitis C is a blood-borne virus that attacks the liver,
causing cirrhosis (liver scarring) and liver cancer, and is
the primary reason many patients undergo liver transplants
in the U.S. An estimated 4 million Americans are chronically
infected with the virus, with about 35,000 new infections
reported each year. The main risk factors associated with
hepatitis C transmission include blood transfusions prior
to 1992 and IV drug use. Tattoos and piercings administered
with non-sterile equipment may also spread hepatitis C.
The study was funded by a research grant from Roche, the manufacturer
of Pegasys and Copegus. Pegasys/Copegus combination therapy
was approved by the U.S. Food and Drug Administration (FDA)
last December for the treatment of adults with chronic hepatitis
C who have stable liver disease and have not previously been
treated with interferon alpha.
About VCU and the VCU Medical Center: Located on two downtown
campuses in Richmond, Va., Virginia Commonwealth University
is ranked nationally by the Carnegie Foundation as a top research
institution and enrolls 26,000 students in more than 170 undergraduate,
graduate, professional and doctoral programs in the arts,
sciences and humanities in 11 schools and one college. Forty
of the university's programs are unique in Virginia, and 20
graduate and professional programs have been ranked by U.S.
News & World Report as among the best of their kind. MCV
Hospitals, clinics and the health sciences schools of Virginia
Commonwealth University compose the VCU Medical Center, one
of the leading academic medical centers in the country. For
more, see www.vcu.edu.
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Idun Pharmaceuticals Reports Positive
Data for First Oral Clinical Trial in HCV Patients
Idun Pharmaceuticals, Inc. today announced positive data from
its oral dose-ranging clinical trial of IDN-6556 for the treatment
of liver impairment caused by Hepatitis C virus (HCV) infection.
The data showed that when given orally, IDN-6556 normalized
liver enzymes after just two weeks of twice-a-day dosing.
Increased levels of aminotransferase enzymes are a well-accepted
indicator of damage in the liver. As was seen in an earlier
trial with an intravenous form of IDN-6556, the drug was safe
and well tolerated, and did not appear to exacerbate the HCV
infection. The data was presented by Paul Pockros, M.D., Head
of the Division of Gastroenterology and Hepatology at Scripps
Clinic (San Diego), at a late- breaking session of the 54th
Annual Meeting of the American Association for the Study of
Liver Diseases (AASLD) in Boston.
"The data is encouraging," Dr. Pockros said. "Together
with the other investigators in the trial, I believe the drug
may be useful in treating a number of liver diseases and will
be studied further in patients with HCV. The study is ongoing
and we hope to present additional data next year on its effects
in patients with other liver diseases, such as fatty liver
disease (NASH) and hepato-biliary disease."
IDN-6556 is a potent inhibitor of the key caspase enzymes
that mediate apoptosis and is designed to protect liver cells
(hepatocytes) from excessive programmed cell death. Increased
rates of apoptosis have been implicated in many different
liver diseases. Unfortunately, individuals suffering from
these conditions have limited treatment alternatives, many
of which are often poorly tolerated, expensive and do not
cure most patients.
The ongoing clinical trial is a double-blind, placebo-controlled,dose-
ranging study being conducted at six major hepatology hospitals
in the United States. The presentation was based on data from
41 patients, over 70% of whom had failed to have an adequate
response with currently approved treatments of HCV (interferon-alpha
and ribavirin).
"The study shows that IDN-6556 can have beneficial effects
in as little as two weeks in patients with HCV," said
David Shapiro, M.D., Idun's Chief Medical Officer. "The
data from this study in HCV-infected patients provides support
for the evaluation of the drug in its oral form in other liver
diseases as well. We are currently developing the plans for
the next set of clinical studies in patients with HCV. We
plan to study the effects of the drug in both patients that
have failed to be successfully treated with the currently
available drugs and, separately, with IDN-6556 given together
with such therapy."
"This data in humans is consistent with the results of
extensive scientific research conducted by Idun and our collaborators,"
said Steven J. Mento, Ph.D., President and CEO of Idun. "It
further supports our view that IDN-6556 may have a major impact
on the treatment of a broad range of liver diseases and encourages
us to proceed with an expanded development program."
Idun also recently announced the initiation of another clinical
trial of IDN-6556 in patients undergoing liver transplantation.
Idun Pharmaceuticals, Inc. is a biopharmaceutical company
located in San Diego, CA, creating innovative human therapeutics
with a primary focus on controlling apoptosis, or programmed
cell death.
Apoptosis is a genetically controlled, normally occurring,
biological process mediated by a cascade of intra-cellular
proteins. Too much or too little apoptosis is believed to
play a role in many important human diseases. Idun believes
that its drug candidates will have utility in treating liver
disease, inflammation, cancer, and cardiovascular disease.
Idun has an extensive patent portfolio covering the fundamental
and core technologies involved in the regulation of cell death.
Back to top
Drug Hope
for Hepatitis C
A new drug has been developed to treat those with hepatitis
C, according to research published online in Nature Immunology
(Nat Immunol 2003; 4(11).
An estimated 170 million people are chronically infected with
HCV. Current therapies are often ineffective and may cause
unpleasant side effects.
In this study, Dr Daniel Lamarre and colleagues designed a
molecule that stops virus particles being made. The drug,
known as BILN 2061, blocks an enzyme that is needed by the
virus for replication.
The team organized the first proof-of-principle study with
human patients.
They assessed 8 patients infected with hepatitis C virus (HCV)
who took 4 doses of the drug over 48 hours.
They found that 2 days later virus levels had dropped by 100-
to 1,000-fold.
No side effects were reported.
Longer trials are needed to assess how the antiviral activity
holds up over time, and whether drug resistance will occur.
Back to top
October 28th, 2003
Pegasys
Found Superior to Current Hepatitis B Treatments
New study shows Pegasys more effective than lamivudine in
most difficult-to-treat form of Hepatitis B disease
In patients infected with the most difficult-to-treat
hepatitis B virus (HBeAg negative or 'variant' HBV), Pegasys
is more effective than lamivudine and the addition of lamivudine
to Pegasys does not provide additional efficacy, according
to results presented at a conference(*) today.
This Phase III study, conducted in 13 countries, is the largest
multinational study of pegylated interferon in patients with
'variant' hepatitis B virus and it is the first large-scale
head-to-head study to compare Roche's pegylated interferon
against lamivudine. Lamivudine is the most commonly used therapy
for infections with the hepatitis B virus.
"With Pegasys, we have for the first time a hepatitis
B therapy which can produce a high sustained treatment response,
and this is extremely encouraging to physicians looking for
treatment solutions," said Professor Patrick Marcellin,
Hepatologist from the Htpital Beaujon, Clichy, France and
the lead investigator for the study. "What is also important
is that with Pegasys we have a defined treatment period, which
is what most patients want."
"These are highly encouraging results for physicians
and patients in the fight against this serious liver infection,"
said William M. Burns, Head of the Pharmaceutical Division
at Roche. "Based on these extremely positive results,
we plan to file Pegasys in hepatitis B with health authorities
next year."
About the study
The 537 patients enrolled in the study, all of whom had HBeAg
negative HBV and raised blood levels of ALT, a specific liver
enzyme serving as a marker for liver inflammation, were treated
for 48 weeks with either Pegasys 180 (g once weekly plus placebo,
lamivudine 100 mg once daily or a combination of the two.
They were then observed for a further 24 weeks with no treatment.
The treatment was considered effective if ALT levels fell
to normal and viral DNA levels, a measure for the concentration
of virus in the bloodstream, were reduced below 20,000 copies/ml
at the end of the follow-up period.
Viral load and ALT levels were significantly affected
At the end of the follow-up period, the study found for the
two primary endpoints that:
* 42.9% of patients treated with Pegasys monotherapy reduced
their hepatitis B viral DNA to less than 20,000 copies per/ml
compared to only 29.3% of those treated with lamivudine. This
result is statistically highly significant. The combination
of Pegasys and lamivudine yielded a reduction in hepatitis
B viral DNA in 44.1% of patients, demonstrating that the addition
of lamivudine to Pegasys does not improve the treatment outcome.
* In addition Pegasys had a better impact on ALT than lamivudine:
59.3 per cent of patients treated with Pegasys had their elevated
ALT levels return to normal; compared to only 44.2% of lamivudine-treated
patients. The combination of Pegasys and lamivudine (59.8%)
was not statistically different to Pegasys alone.
Patients typically relapse after treatment is stopped
HBeAg negative HBV, also known as 'variant' or 'pre-core mutant'
hepatitis B, is caused by a genetic mutation to the virus.
Patients infected with the HBeAg negative HBV are more likely
to have severe destructive inflammatory changes to their liver
and fibrosis when they first see their physician than those
infected with the HBeAg positive disease. Patients typically
relapse after treatment is stopped.
HBeAg negative HBV accounts for approximately 40 per cent
of cases in the US and over 80 per cent of cases in Southern
Europe.
"We have shown previously that Pegasys is an effective
treatment for the more common HBeAg-positive strain of HBV,(i)"
said Professor Graham Cooksley, Senior Principal Research
Fellow, Clinical Research Centre, Royal Brisbane Hospital,
Australia. "These results mean we can now also use Pegasys
with confidence to treat patients with the more challenging
HBeAg negative strain of the disease."
About Hepatitis B
Hepatitis B is a blood-born virus that attacks the liver and
is the most common serious liver infection in the world. The
hepatitis B virus is highly contagious and is relatively easy
to transmit from one infected individual to another. It is
100 times more infectious than the HIV virus.
Despite a highly effective vaccine, more than two billion
people have been infected by HBV and 350 million people have
chronic infection, which can be easily transmitted by blood-to-blood
contact, during birth, sex, and by sharing needles. HBV and
HCV rank among the top four causes of cancer deaths in most
countries in Asia and the Western Pacific rim.(ii) For those
chronically infected with HBV, treatment is the only option.
About Pegasys
Pegasys, a new generation hepatitis therapy that is different
by design, provides significant benefit over conventional
interferon therapy in patients infected with HBV and HCV.
The benefits of Pegasys are derived from its new generation
large 40 kilodalton branched-chain polyethylene glycol (PEG)
construction, which allows for constant viral suppression
over the course of a full week. Pegasys also distributes more
readily to the liver (the primary site of infection) than
conventional interferon. In HCV Pegasys provides superior
efficacy compared to conventional interferon combination therapy
in HCV patients of all genotypes. Pegasys is the only pegylated
interferon available as a ready-to-administer solution. Each
weekly subcutaneous injection contains 180 mcg of pegylated
interferon alfa-2a which is the approved dose for all patients,
regardless of body weight.
Roche in hepatitis
Roche is committed to the viral hepatitis disease area, having
introduced Roferon-A for hepatitis B and C, followed by Pegasys
in hepatitis C and now Pegasys also demonstrates superior
efficacy over current treatments: conventional interferon
and lamivudine in hepatitis B. Roche has also launched its
own brand of ribavirin, Copegus, to be used in conjunction
with Roferon A or Pegasys for HCV. Roche also manufactures
HBV and HCV diagnostic and monitoring systems: The COBAS AMPLICOR(tm)
Test, and the AMPLICOR(tm) MONITOR Test, two testing systems
used to detect the presence of, and quantity of, HBV DNA or
HCV RNA in a person's blood. Roche's commitment to hepatitis
has been further reinforced by the in-licensing of Levovirin,
an alternative antiviral. Levovirin will be studied with the
objective of demonstrating superior tolerability over the
current standard, ribavirin.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world's
leading innovation-driven healthcare groups. Its core businesses
are pharmaceuticals and diagnostics. Roche is number one in
the global diagnostics market, the leading supplier of pharmaceuticals
for cancer and a leader in virology and transplantation. As
a supplier of products and services for the prevention, diagnosis
and treatment of disease, the Group contributes on a broad
range of fronts to improving people's health and quality of
life. Roche employs roughly 65,000 people in 150 countries.
The Group has alliances and R&D agreements with numerous
partners, including majority ownership interests in Genentech
and Chugai.
All trademarks used or mentioned in this release are legally
protected.
(*) 54th American Association for the Study of Liver Diseases
(AASLD) Annual Meeting
NOTES TO THE EDITOR:
* New guidelines on HBV were recently developed by the European
Association for the Study of Liver (EASL).(iii) Conventional
interferon monotherapy was recommended as the first therapeutic
approach when treating these patients. The EASL Jury noted
however, that the optimal treatment of hepatitis B will require
regular revision in the light of new data.
References:
(i) Cooksley, W. Graham E et al. Peginterferon alfa-2a (40KD):
An advance in the treatment of HBeAg-Positive Chronic Hepatitis
B. J. Viral Hepatitis. 2003;10:298-305
(ii) Chu, CM. Natural History of Chronic Hepatitis B Virus
Infection in Adults with Emphasis on the Occurrence of Cirrhosis
and Hepatocellular carcinoma. J Gastroenterol. Hepatol.
2000;15 (suppl.):E25-30.
(iii) EASL International Consensus Conference on Hepatitis
B. 13-14 September, 2002: Geneva, Switzerland. Consensus statement
(short version). J Hepatol, 2003.38:533-40.
Contact: F. Hoffmann-La Roche Ltd, Corporate Communications,
Tel: +41 (0)61 - 688 88 88, Fax: +41 (0)61 - 688 27 75, http://www.roche.com/
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Cirrhotic
Patients with Spontaneous Bacterial Peritonitis
gastrohep.com
Patients with spontaneous bacterial peritonitis frequently
develop a rapidly progressive impairment in systemic hemodynamics,
find researchers in the November issue of Hepatology
(Hepatology 2003; 38: 1210-18). Spontaneous bacterial
peritonitis is frequently associated with renal failure.
8 patients developed renal failure during treatment.
In this study, researchers from Spain assessed whether systemic
and hepatic hemodynamics were also altered by this condition.
The team evaluated 23 patients with spontaneous bacterial
peritonitis, both at diagnosis and after infection resolution.
They assessed tumor necrosis factor alpha (TNF-alpha) in plasma
and ascitic fluid, plasma renin activity (PRA) and norepinephrine
(NE), as well as systemic and hepatic hemodynamics.
The team found that 8 of the patients developed renal failure
during treatment. At diagnosis, these patients had higher
levels of TNF-alpha, blood urea nitrogen (BUN), PRA and NE,
peripheral vascular resistance, and hepatic venous pressure
gradient (HVPG) and lower cardiac output.
The team determined that changes in PRA and NE correlated
inversely with changes in arterial pressure and directly with
changes in BUN, Child-Pugh score, and HVPG.
There were 5 patients in the renal failure group who developed
encephalopathy. Overall, 6 patients in this group died.
Dr Luis Ruiz-del-Arbol’s team concluded, “Patients
with spontaneous bacterial peritonitis frequently develop
a rapidly progressive impairment in systemic hemodynamics”.
This leads to, “Severe renal and hepatic failure, aggravation
of portal hypertension, encephalopathy, and death”.
“This occurs despite rapid resolution of infection and
is associated with an extremely poor prognosis”.
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Cultures Of Human Fetal Hepatocytes
gastrohep.com
Human fetal hepatocyte cultures are an excellent tool for
a variety of studies with human hepatocytes, find scientists
in the November issue of Hepatology (Hepatology
2003; 38: 1095-1106).
Cultured human hepatocytes have broad research and clinical
applications.
However, culturing these cells is difficult.
There can be rapid loss of the hepatocytic phenotype in primary
culture, and a limited replicating capacity of the cultured
cells.
In this study, scientists from Australia and the United States
describe the establishment of serum-free primary cultures
of human fetal hepatocytes.
These cultures retained their hepatocytic morphology and gene
expression patterns for several months. They also maintained
sufficient proliferative activity to permit subculturing for
at least 2 passages.
The team found that the human fetal hepatocyte cultures contained
2 main cell types, which morphologically resembled large and
small hepatocytes. The cells expressed alpha-fetoprotein,
cytokeratin 19, albumin, and other hepatic proteins.
The scientists determined that treatment of the cultures with
oncostatin M increased cell size, and enhanced cell differentiation
and formation of bile canaliculi. This may have been due to
an effect on hepatocyte nuclear factor 4.
They found that a month after plating, multiple clusters of
very small cells became apparent in the cultures. These cells
had very few organelles and the team referred to them as blast-like
cells.
Flow cytometric analysis of these cells showed that they express
oval cell/stem cell markers such as CD90 (Thy-1), CD34, and
OV-6, However, they do not stain with antibodies to 2-microglobulin.
The scientists determined that human fetal hepatocyte cultures
maintained for 9 to 12 months produced grossly visible organoids.
These contained ductular structures that stained for cytokeratin
18 and 19, and alpha-fetoprotein.
Dr Catherine Lazaro’s team concluded, “Human fetal
hepatocyte cultures ... constitute an excellent tool for a
variety of studies with human hepatocytes, including the mechanisms
of viral infection”.
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Idenix
Pharmaceuticals Presents Positive 1-Year Data On Telbivudine(LdT)
For The Treatment Of Chronic Hepatitis B
PRNewswire
Idenix Pharmaceuticals, Inc. today presented final 52-week
results from an international phase IIbclinical trial of its
lead drug candidate, telbivudine (LdT), at the54th Annual
Meeting of the American Association for the Study ofLiver
Diseases (AASLD) in Boston, Massachusetts.
This trial compared treatment with telbivudine alone or telbivudine
in combination with lamivudine, with lamivudine monotherapy
in patients with chronic hepatitis B. The study demonstrated
significantly better suppression of hepatitis B virus (HBV)
replication and normalization of ALT (ameasure of liver disease)
with telbivudine compared to lamivudine monotherapy. Additional
analyses of the study data suggested that the strong, early
antiviral effect seen with telbivudine therapy is associated
with improved clinical efficacy outcomes at 1 year.
Telbivudine induced rapid and marked reductions in the levels
of hepatitis B virus (HBV) circulating in the blood stream.
After one year, serum virus levels, measured as serum HBV
DNA levels, were reduced by a mean 6 log10 (1 million-fold)
in patients receiving telbivudine, a significantly greater
antiviral response compared with patients receiving lamivudine
alone (4.57 log10 reduction, or 50,000-fold). HBV
became undetectable in the serum of 61% of patients receiving
telbivudine monotherapy, nearly double the 32% response rate
of patients in the lamivudine monotherapy group. Serum ALT
levels (a measure of liver disease) became normal in 86% of
patients in the telbivudine monotherapy groups, significantly
more than the 63% of patients in the lamivudine monotherapy
group who achieved this response.
“These data confirm the potent antiviral effect of telbivudine
through 52 weeks,” said Ching-Lung Lai, M.D., lead investigator
and Professor of Medicine at the University of Hong Kong.
“The excellent safety profile, the potent and sustained
suppression of hepatitis B virus, and the serologic evidence
of greater reduction of liver inflammation with telbivudine
treatment suggest that telbivudine will offer a promising
new treatment option for patients with hepatitis B virus infection.”
Study Description
The randomized, double-blind phase IIb clinical trial compared
the safety and antiviral effectiveness of telbivudine, and
telbivudine in combination with lamivudine, with a control
arm of lamivudine alone. The study enrolled 104 adults with
chronic hepatitis B. The average age of patients in the trial
was 37 years (range: 18-68 years).
The trial was conducted at 16 sites in Hong Kong, Singapore,
France, Canada and the United States. In the study, eligible
patients were randomized to one of five daily treatment regimens,
as follows:
telbivudine 400 mg, telbivudine 600 mg, telbivudine 400 mg
+ lamivudine 100 mg, telbivudine 600 mg + lamivudine 100 mg
or standard lamivudine therapy (100 mg per day). All patients
were dosed orally once daily for a treatment period of one
year. At baseline, patients had a median serum viral load
(HBV DNA level) exceeding one billion virus particles per
milliliter (9.28 log10), and the five treatment
groups were well matched for demographic and disease features.
Study Results
After 52 weeks, patients receiving a telbivudine-containing
treatment achieved a mean reduction in viral load (serum HBV
DNA) of one million fold (6 log10) from the level
at baseline. The mean reductions from baseline for the three
types of treatment are as follows: 6.01 log10 for
telbivudine monotherapy; 5.99 log10 for the telbivudine/lamivudine
combination arm; 4.57 log10 for lamivudine monotherapy
(p<0.05 telbivudine monotherapy vs. lamivudine monotherapy).
Virus levels in serum became undetectable by a highly sensitive
polymerase chain reaction (PCR) assay in 61% of patients receiving
telbivudine, 49% of patients receiving telbivudine/lamivudine
combination with lamivudine and 32% of patients receiving
lamivudine monotherapy (p<0.05 telbivudine monotherapy
vs. lamivudine monotherapy).
Study results also show that the majority of telbivudine-treated
patients achieved early and sustained normalization of serum
ALT levels, suggesting reduced underlying HBV-related liver
inflammation. Among patients receiving telbivudine monotherapy,
86% achieved normalized ALT levels, compared to 63% of patients
receiving lamivudine monotherapy (p<0.05 telbivudine monotherapy
arms vs. lamivudine monotherapy).
Data from all study patients regardless of treatment group
were combined to assess the effect of viral suppression on
clinically relevant endpoints at 1 year. Analysis showed that
patients achieving an early and profound degree of viral suppression
experienced the greatest improvement in measures associated
with clinical benefit at one year. These measures include
e antigen seroconversion (a predictor of disease remission),
serum ALT normalization (a marker of reduced liver inflammation)
and undetectable levels of HBV DNA.
Upon evaluation of the telbivudine / lamivudine combination
treatment arms, the data showed improvements in antiviral
efficacy when compared to lamivudine monotherapy but there
was no advantage with respect to either antiviral or clinical
effects of the telbivudine/lamivudine combination treatment
over telbivudine alone.
Throughout the phase IIb clinical trial, no safety issues
have been identified through week 52 for any of the five treatment
regimens. There were no drug-attributed serious adverse events,
and no pattern of dose-related or treatment-related clinical
side effects or laboratory abnormalities.
“Chronic hepatitis B remains a serious global disease.
Although remarkable advances in the treatment of hepatitis
B have been achieved in recent years, current treatments remain
only partially effective and further improvements are needed,”
said Nathaniel Brown, M.D., Idenix’ Senior Vice President
and Chief Medical Officer. “The progression of HBV-induced
liver disease is linked to ongoing viral replication. The
data from this study indicate that the marked inhibition of
viral replication observed with telbivudine is likely to be
associated with improved clinical efficacy.”
Clinical Development of Telbivudine
The positive phase IIb clinical data support the ongoing large-scale
phase III program initiated in 2003. The pivotal phase III
program, upon which global registrations will be based, will
involve 1,200 patients in over 130 clinical sites in 20 countries
in Asia, North America and Europe. It will include HBeAg+
and HBeAg- patients with compensated liver disease evaluated
for therapeutic response. It will be the principal efficacy
study for global product registrations of telbivudine.
About hepatitis B:
Despite the presence of global immunization programs for hepatitis
B virus, approximately 350 million people, or 5% of the world’s
population, is chronically infected with hepatitis B virus.
Approximately 33% of these individuals have potentially progressive
and life-threatening liver disease associated with their chronic
HBV infection. Chronic hepatitis B can lead to cirrhosis,
liver failure and hepatocellular carcinoma (liver cancer).
Globally, this year, 10 to 30 million more people will become
infected with hepatitis B virus and more than one million
individuals will die from HBV-related chronic liver disease
demonstrating the urgent need for new treatment and for improved
public health measures to identify “silent” HBV
carriers with underlying liver disease.
About Idenix:
Idenix Pharmaceuticals, Inc. is a biopharmaceutical
company engaged in the discovery and development of drugs
for the treatment of human viral and other infectious diseases.
Idenix’ current focus is on the treatment of infections
caused by hepatitis B virus, hepatitis C virus and human immunodeficiency
virus (HIV). Idenix is headquartered in Cambridge, Massachusetts
and has drug discovery operations in Montpellier, France and
Cagliari, Italy.
In May 2003, Idenix and Novartis Pharma AG entered into a
broad collaboration on the development and commercialization
of Idenix’ pipeline, including Idenix’ hepatitis
B drug candidates. The collaboration also provides Novartis
with an exclusive option to license and participate with Idenix
in the development and commercialization of other drug candidates
in Idenix’ portfolio, including Idenix’ hepatitis
C compounds. In addition to license fee payments and reimbursement
of certain expenses, Novartis will make payments to Idenix
contingent on milestones being achieved for Idenix drug candidates
that Novartis selects to jointly develop and commercialize
as part of the collaboration.
For further information about Idenix, please refer to http://www.idenix.com/.
Contact: Idenix Pharmaceuticals, Inc. Euro RSCG Life NRP (617)
250-
3119 (212) 845-4200 Teri Babine Lynn Blenkhorn (media) x 4276
Idenix
Public Relations Donald Murphy x 4274
Idenix Pharmaceuticals, Inc.
CONTACT: Teri Babine, Idenix Public Relations, +1-617-250-3119;
or LynnBlenkhorn (media) x 4276, or Donald Murphy x 4274,
both of Euro RSCG Life NRP,+1-212-845-4200, for Idenix Pharmaceuticals,
Inc.
Web site: http://www.idenix.com/
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October 29th, 2003
Management
Of Hepatocellular Carcinoma Larger Than 10 Cm
gastrohep.com
The advantage of hepatic resection in patients with huge hepatocellular
carcinoma is marginal, find doctors in the latest issue of
the Journal of the American College of Surgeons (J
Am Coll Surg 2003; 197(5): 730-8).
Resection for large hepatocellular carcinoma (HCC) is challenging.
However, the role of multimodality nonsurgical therapy for
HCC greater than 10 cm is unclear.
In this study, doctors from Taiwan investigated 131 HCC patients
with tumors larger than 10 cm, between 1990 and 2001.
The 56 patients in group A underwent hepatectomy, while the
75 patients in group B underwent nonsurgical multidisciplinary
therapy. The nonsurgical therapy included hepatic arterial
infusion, transcatheter arterial embolization, and percutaneous
acetic acid injection. Younger patients had a higher prevalence
of hepatitis B surface antigen positivity.
The team determined that the patients in group B were older
and had lower serum albumin levels. This group also contained
more patients with liver cirrhosis and great vessel invasion.
The doctors found that the median survival of patients in
group A was 17 months, compared with 7 months for patients
in group B.
However, 1-, 3-, and 5-year survival rates for group B patients
who underwent 3 or more treatment sessions were not significantly
worse than those for group A.
The team found that patients in group A had 38% and 72% recurrence
rates at 6 and 12 months, respectively. They also had a significantly
higher frequency of overall extrahepatic recurrence.
They also determined that 3 of 35 group B patients younger
than 60 years had tumor shrinkage after nonsurgical treatment,
compared with 17 of 40 patients over 60.
The younger patients tended to have a higher prevalence of
hepatitis B surface antigen positivity and infiltrating tumor
growth pattern, compared with older patients.
Dr King-Tong Mok’s team concluded, “Our study
suggests that the advantage of hepatic resection in patients
with huge HCC is marginal”.
“An effective adjuvant therapy is needed to improve
outcomes after hepatic resection”.
“The experience in using nonsurgical treatment shows
that the result is poor in young patients compared with that
in elderly patients”.
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October 31st, 2003
Severe
Hepatitis C-Related Liver Damage Following Liver Transplantation
gastrohep.com
Delayed hepatitis C-related severe liver damage occurs in
over one third of liver transplant recipients with initial
benign recurrence, find physicians in the November issue of
Liver Transplantation (Liver Transpl 2003;
9: 1152-8).
Histological hepatitis occurs in the majority of hepatitis
C virus (HCV)-infected liver transplant recipients. Its natural
history is highly variable.
Prolonged follow-up has suggested that some patients with
initial benign recurrence may develop a late-onset aggressive
course.
In this study, physicians from Spain determined the incidence
and factors associated with late-onset severe hepatitis C.
The team evaluated the histological outcome of 57 HCV type
1b-infected transplant recipients with initial benign recurrence.
They defined severe late-onset liver damage as progression
to F3 or F4 after previous benign recurrence.
Severe late-onset liver damage occurred in 35% of patients.
The physicians found that severe late-onset liver damage occurred
in 35% of patients.
They determined that 12 transplant recipients progressed to
F3 and 8 progressed to F4.
The team identified baseline fibrosis stage and activity grade,
female gender, alanine aminotransferase (ALT) level at 1 year,
and baseline aspartate aminotransferase (AST) and ALT levels
as factors influencing late-onset disease.
However, multivariate analysis found only fibrosis stage at
baseline a significant factor.
Dr Marina Berenguer’s team concluded, “Delayed
HCV-related severe liver damage is not infrequent in transplant
recipients with initial benign recurrence, occurring in approximately
one third of them”.
“The presence of some degree of fibrosis at baseline
appears to predict this sudden change in the natural history
of recurrent hepatitis C”.
“Based on these findings, we recommend continuing protocol
biopsies and evaluating potential antiviral therapy in transplant
recipients with evidence of some fibrosis”.
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Health-Related
Quality Of Life In Long-Term Liver Transplant Survivors
gastrohep.com
Patients who survive for more than 10 years after liver transplantation
have significant cognitive dysfunction and poor health-related
quality of life, find researchers in the November issue of
Liver Transplantation ( Liver Transpl 2003;
9: 1145-8).
Several studies have investigated short-term effects of liver
transplantation on cognitive function and health-related quality
of life. However, there have been no studies which examine
long-term effects.
In this study, a research team from Leeds, England examined
36 patients who had received a single liver transplant at
St James’s University Hospital prior to 1991.
The team assessed patients’ cognitive function using
the Mini-Mental State Examination, the Rey Auditory Verbal
Learning Test, trail-making tests, the Stroop test, and the
Benton Visual Retention Test.
They also evaluated anxiety and depression using the Hospital
Anxiety and Depression Scale. In addition, patients’
health-related quality of life was assessed using the EuroQol.
Of the 36 patients, the team included 12 in the study. Patients
were compared to 25 healthy controls.
The researchers found that, compared to the controls, patients
scored significantly lower on measures of health-related quality
of life. However, the team detected no differences in levels
of anxiety or depression.
They also found that patients scored significantly lower than
controls across a wide range of cognitive functions.
Drs Mark Lewis and Peter Howdle concluded, “Patients
who survive for more than 10 years after liver transplantation
have significant cognitive dysfunction and poor health-related
quality of life”.
“Whether these patients never return to normal after
transplantation or whether they experience an increased rate
of decline in cognitive function and health-related quality
of life is uncertain”.
In a related editorial in the same publication, Dr Kathleen
Moore from Deakin University, Melbourne, Australia, also discusses
quality of life following liver transplantation.
Dr Moore concludes, that much more research is required in
order “To ascertain the long-term impact of liver transplantation
on recipients’ cognitive functioning”.
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Survival
of Recipients Of Liver Grafts From Donors Over 80 Years
gastrohep.com
The use of grafts from older donors is safe for orthotopic
liver transplantation, find doctors in the latest issue of
Liver Transplantation (Liver Transpl 2003; 9:
1174-80).
Orthotopic liver transplantation (OLT) using grafts from donors
older than 80 years have been reported. However, the long-term
outcome of patients receiving livers from these donors is
unknown.
In this study, doctors from Italy evaluated 12 patients who
received OLTs between 1998 and 2003. Donors were over 80 years.
More than a years worth of follow-up data were available.
The team found that hepatic insufficiency caused by hepatitis
C virus (HCV)-related cirrhosis occurred in 42% of patients,
and non-HCV-related diseases in 58%.
Transplantation was uneventful in all cases.
All donors had normal liver function, hemodynamic stability,
and no parenchymal alterations.
The doctors found that OLT was uneventful in all cases, and
no late vascular complications occurred.
One patient died 3 years after OLT for
causes unrelated to hepatic dysfunction.
The team calculated 2 and 3-year actuarial survival rates
as 100% and 75%, respectively.
All HCV-positive patients developed hepatitis recurrence requiring
antiviral treatment.
However, non-HCV-positive patients had well-preserved liver
function throughout the observation period.
By the end of follow-up, the team observed
no clinical hepatic decompensation.
Biochemical signs of recurrent disease were noted in 3 patients.
Dr Matteo Cescon’s team concluded, “Use of grafts
for OLT from donors older than 80 years is safe because of
their potentially normal functional recovery”.
“A selection among available organs is mandatory to
minimize other risk factors for poor outcome”.
“Long-term patient and graft survival seem to be achievable,
but the high rate and rapidity of HCV reinfection remain a
major concern for HCV+ patients”.
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Virus-Related
Muscle Damage Tied To Chronic Fatigue
Reuters Health
Chronic fatigue syndrome seems to occur sometimes after a
virus infection. Now, researchers have shown that some patients
with the syndrome have evidence of virus in their muscles,
and this in turn is linked to abnormal muscle function.
Dr. R. J. M. Lane and others at Imperial College in London,
UK, looked for RNA from enteroviruses in muscle biopsies taken
from 48 patients with chronic fatigue syndrome and from 29
people with normal muscles Muscle biopsy samples from 10 of
the 48 chronic fatigue patients were positive for enterovirus
RNA, Lane’s team reports in the Journal of Neurology,
Neurosurgery, and Psychiatry."All 29 human tissue controls...were
negative for enterovirus sequences."
The investigators say the RNA most closely that from coxsackie
B virus.
In addition, the patients with chronic fatigue syndrome went
through an exercise test on the day of the biopsy, and the
researchers measured the patients’ blood levels of lactic
acid before and after the test.
Twenty-eight patients had an abnormal lactate response to
exercise, “reflecting impaired muscle energy metabolism.”
Moreover, 9 of the 10 subjects who tested positive for the
presence of virus in their muscles had this abnormal response.
The team concludes that their findings support the notion
that chronic fatigue syndrome has different causes, “and
that some cases have a peripheral component to their fatigue
related to muscle dysfunction.”
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Transplant
Extends Survival ln Liver Cancer Patients
Reuters Health
The outcome of liver transplantation inpatients with liver
cancer has improved over the last decade, investigatorsreport
in an upcoming issue of the Journal of Clinical Oncology.
Currently,more than half of these patients survive beyond
five years.
Using data from the United Network for Organ Sharing database,
Dr. Paul J. Thuluvath and associates at Johns Hopkins University
Hospital, Baltimore, identified patients who underwent liver
transplantation in the US between 1987 and 2001.
Included in their analysis were 985 patients whose transplant
was performed to treat liver cancer and more than 33,000 patients
who received a transplant for nonmalignant liver conditions,
which served as a comparison group, or “control”
group.
Overall five-year survival rate was 42.3 percent for the liver
cancer group and 71.7 percent in the control group. However,
five-year survival rate for cancer patients increased steadily
over time from 25.3 percent between 1987 and 1991, to 61.1
percent between 1997 and 2001.
The authors attribute the reduced death rate over time to
careful patient selection based on published treatment guidelines.
They note that only about 20 percent of patients with cirrhosis
and liver cancer are appropriate candidates for liver surgery,
and that five-year survival rates after surgery are only about
30 percent.
Transplantation offers the advantages of complete tumor removal
and cure of underlying liver disease.
Thuluvath and associates conclude that “liver transplantation
is the treatment of choice in patients with advanced cirrhosis
and [liver cancer].”
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Designer
Transplant Drug Shows Promise In Monkeys Compound May Block
Organ Rejection Without Side-Effects
by Helen Pearson
25,000 Americans received an organ transplant last year.
A designer drug stops organ transplants being rejected - without
the typical side-effects seen in monkey experiments, its makers
say.
Medicines currently used to protect transplanted hearts, kidneys
and livers can have noxious knock-on effects. Heart disease
and kidney damage now kill more transplant patients than organ
rejection itself, experts say.
The new drug, CP-690,550, helped macaques live for up to 90
days after a life-saving kidney transplant, compared to just
six days without it. What’s more, they say that the
monkeys suffered relatively few adverse reactions. “I
think the story is pretty exciting,” says Dominic Borie
of Stanford University in California who led the animal experiments.
CP-690,550 was designed to block an enzyme, JAK3, that normally
helps immune cells called lymphocytes to attack a transplanted
organ.
The concept “is revolutionary”, says transplant
specialist Barry Kahan of the University of Texas Medical
School in Houston. The treatment is being pursued by other
labs and companies.
Under attack
Around 25,000 patients received organ transplants last year
in the United States alone. A foreign organ makes surrounding
tissues release chemicals called cytokines. These tell lymphocytes
to attack the transplanted tissue.
To avert this, transplant patients swallow a cocktail of immunosuppressive
drugs for the rest of their lives. These drugs are toxic partly
because they act on other tissues besides immune cells.
The hope is that CP-690,550 will bypass side-effects because
JAK3 is present only in the lymphocytes that drive organ rejection.
Researchers at Pfizer in Groton, Connecticut, found CP-690,550
by screening a collection of chemical compounds for one that
inhibits JAK3 and then tinkering with its chemical structure.
Preliminary clinical trials suggest that CP-690,550 is safe
in people, says Pfizer immunologist Paul Changelian. His team
is now trying it on patients with psoriasis, a condition in
which an overactive immune system affects the skin. The drug
will take at least five years to clear through all clinical
trials, he says.
The drug could still have side-effects. Many of the 12 monkeys
in the trial fell ill after receiving high doses, Kahan points
out. CP-690,550 might be interfering with a sister enzyme,
JAK2, which controls production of red blood cells. So the
molecule - or others like it - may need some tweaking to make
a next-generation drug, Kahan cautions.
References
Changelian, P. S. et al. Prevention of organ allograft rejection
by a specific Janus Kinase 3 inhibitor. Science,
302, 875 - 878, (2003).
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