HCV Advocate EASL 2008 Coverage
- Liver Diseases: A Huge European Health Burden, But Some Trends Are Positive
- Study shows positive findings in treating patients with advanced hepatitis C
- Biolex Therapeutics Researchers Present Locteron(R) Phase 2a Hepatitis C Trial Results at EASL Conference
- Pharmasset Adds Two Cohorts to R7128 Hepatitis C Study
- Vertex reports promising hepatitis C drug results
- Pharmasset Presents Results of 4-Week Combination Study of R7128 for the Treatment of Chronic Hepatitis C
- Data On Investigational Compounds Being Co-Developed By Tibotec For The Treatment Of Chronic Hepatitis C Presented At EASL 2008
- Three Studies Presented at 43rd EASL Strongly Indicate Better Efficacy for PEGASYS in Curing Hepatitis C
- Roche's R1626, First-in-Class Hepatitis C Polymerase Inhibitor, Demonstrates Impressive End-of-Treatment Response in Phase IIa Study
- Vertex Announces Positive Interim Results with Telaprevir-based . Therapy in Genotype 1 Chronic Hepatitis C Patients who Failed to Achieve S SVR with a previous pegylated interferon and ribavirin treatment regimen.
- Interim Results From Boceprevir Phase II Study In Genotype 1 Treatment-Naive Hepatitis C Patients Presented At EASL
- Gilead Announces 72-Week Data From Two Pivotal Phase III Studies Evaluating Viread(R) for the Treatment of Chronic Hepatitis B
- Clinical Update - Debio 025 in Hepatitis C
- Baraclude (Entecavir) Treatment Resulted In Greater Viral Load Suppression Compared to Adefovir at 96 Weeks In Antiviral-Naive Adult Chronic Hepatitis B E-Antigen Positive Patients
- Nitazoxanide Demonstrates Activity in Treatment-Naive Patients With Hepatitis C Virus Genotype 4: Presented at EASL
- Idenix Pharmaceuticals Presents Positive Preclinical Data on HCV Programs at The Annual Meeting of The European Association for the Study of the Liver (EASL)
Liver Diseases: A Huge European Health Burden, But Some Trends Are Positive
- 29 Million EU Citizens (6%) Have Liver
Diseases, 5th Most Common Cause of Death
- Yearly, Liver Cancer Alone Takes 40,000
Lives; Alcohol Abuse Takes 13,000
- Number With Fatty Liver Disease Stable
or Growing; Viral Hepatitis Declines
More than 6,000 physicians and scientists from around the
world gathered today in this historic Italian city to attend the opening
sessions of the 43rd Annual Meeting of the European Association for the Study
of the Liver (EASL), which runs until April 27th. Not surprisingly, several of
the first presentations focused on trends in the prevalence of each of the
major liver diseases, including continuing declines in new cases of hepatitis B
and C, but stability or increases in fatty liver disease due either to
excessive consumption of alcohol or non-alcoholic causes (NAFLD - non-alcoholic
fatty liver disease).
Hepatologists (liver disease specialists) study and treat a
variety of acute and chronic conditions affecting this largest internal organ
of the body. The acute category includes diseases that typically result from
inflammation or infection due to injurious agents such as viruses, alcohol, and
drugs. The most prominent conditions - each of which may arise in an acute form
but then progress to a chronic state -- are alcoholic liver disease; hepatitis
B, C, and D; non-alcoholic fatty liver disease (NAFLD); and NASH (non-alcoholic
steatohepatitis, the most severe subset of NAFLD).
The transition from an acute to a chronic state occurs when the patient fails to recover and the acute
infection or disease produces ongoing damage to the liver. Cirrhosis - which
refers to the death of liver cells, altered cell regeneration, deposition of
fibrous scar tissue, and ultimately the impairment of liver function -
represents the final stage of many chronic liver diseases. Cirrhosis can only
partially be reversed, but treatments can stop or slow its progression. When
uncontrollable complications of cirrhosis occur, or when damage precludes
sufficient liver function, a liver transplant becomes necessary. Cirrhosis is
the major risk factor for the development of hepatocellular carcinoma (HCC), a
primary cancer of liver cells, which may also require transplantation.
Estimates suggest 10 million carriers of viral hepatitis in
Despite improved prevention, diagnosis, and treatment, the
overall costs of liver disease remain very high because of an increase
prevalence of selected conditions, and the common progression to a chronic
state possibly leading to life-threatening complications.
About EASL
The European Association for the Study of the Liver (EASL)
aims to promote investigation into liver disease and improve the treatments
that currently exist for these conditions. The association, through its annual
meetings, seeks to inform and educate both the scientific community as well as
society in general about the increasing occurrence of liver diseases along with
the importance of understanding these conditions in order to treat and prevent
them. Since its creation in 1966, the EASL congress has been hosted in 20
different European countries. Currently the association has over 1400 members
and the annual congress attracts over 6000 delegates from over 65 countries
each year.
Study shows positive findings in treating patients with advanced hepatitis C
MILAN, ITALY, April 24, 2008 – The hepatitis C therapy peginterferon
alfa-2b, when given as low-dose maintenance therapy, can prevent disease
progression in certain patients who failed previous interferon-based hepatitis
C therapies and have advanced liver disease, according to findings from a
large, four-year study presented today at the 43rd annual meeting of the
European Association for the Study of the Liver (EASL).
The study, called COPILOT
(COlchicine versus Peg-Intron LOng-Term), showed that low-dose
peginterferon alfa-2b was superior to colchicine in improving the disease-free
survival of patients with cirrhosis and portal hypertension, especially in
patients who stayed on treatment. In the study, more than 40 percent of
patients had portal hypertension, a condition of high blood pressure in the
major vessel going to the liver from the gastrointestinal tract and which often
accompanies liver cirrhosis. However, peginterferon alfa-2b maintenance therapy
was not superior to colchicine in patients overall.
“These findings make a strong case for considering low-dose
peginterferon alfa-2b as a maintenance therapy in patients with cirrhosis and
portal hypertension who have failed hepatitis C eradication therapy,” said
principal investigator Nezam Afdhal, M.D., Chief of Hepatology at Beth Israel
Deaconess Medical Center (BIDMC) and Associate Professor of Medicine at Harvard
Medical School. “While other interferon maintenance therapies have been studied
in the past few years in previous interferon nonresponders, these findings
show, for the first time, a clinical benefit in a specific population with
advanced disease,” he said.
Hepatitis C virus (HCV) infection is transmitted through
exposure to infected blood and affects an estimated 4 million individuals in
the
Conducted at approximately 40 sites in the United States,
the COPILOT study compared weight-based low-dose peginterferon alfa-2b
(subcutaneous injection of 0.5 mcg/kg/wk, one-third the dose used in standard
HCV combination therapy) versus colchicine (0.6 mg orally, twice daily), an
anti-inflammatory and antifibrotic medication, in 555 chronic hepatitis C
patients with advanced liver fibrosis who previously failed interferon-based therapies.
Patient baseline characteristics were well balanced between the two study arms.
Over the four years of the randomized study, investigators monitored the
patients to determine how many reached a primary endpoint, defined as death,
liver transplant, hepatocellular carcinoma (liver cancer), variceal bleeding,
or liver failure (increase in Child-Pugh-Turcotte [CPT] by 2 points with
ascites, jaundice or encephalopathy). They analyzed their findings for all 555
patients, who received at least one dose of their assigned drug, in two ways:
based on all events that occurred during the entire four years of the study,
regardless of whether a patient was still taking their assigned drug or not
(the “intent-to-treat” or ITT analysis), and based on only the events that
occurred while patients were taking their assigned drug (the “on drug”
analysis).
The investigators found a primary endpoint was reached by
17.8% (51/286) of patients in the peginterferon alfa-2b group versus 20.4%
(55/269) in the colchicine group in the ITT analysis, and by 12.2% (35/286) and
16.0% (43/269) patients, respectively, in the on-drug analysis (treatment
differences were not statistically significant). Among patients who had portal
hypertension (42.3% and 48.0% of patients in the peginterferon alfa-2b and
colchicine groups, respectively), peginterferon alfa-2b therapy resulted in
significantly improved event-free survival in both the ITT and on-drug analyses
(Wilcoxon p = 0.041 and 0.028, respectively). Further, variceal bleeding, a
specific complication of portal hypertension, was almost abolished with
peginterferon alfa-2b in both the ITT (10 vs. 1 patients) and the on-drug (10
vs. 0 patients) analyses. In the ITT analysis, hepatocellular carcinoma
occurred in 7.7% and 5.9% of patients in the peginterferon alfa-2b and
colchicine groups, respectively, a non-significant difference.
Overall, 49% of patients discontinued their medication
before the end of the four-year study, with 36% due to failure to comply and
13% due to side effects. Peginterferon alfa-2b was generally well tolerated.
Among patients who discontinued due to interferon side effects (17.1%, 49/286),
the most common reason (45%, 22/49 patients) was general intolerance to
interferon (e.g., due to flu-like symptoms, malaise, and other common
interferon side effects).
###
The COPILOT study was
supported by Schering-Plough Corporation, manufacturer of peginterferon
alfa-2b.
Biolex Therapeutics Researchers Present Locteron(R) Phase 2a Hepatitis C Trial Results at EASL Conference
SELECT-1 was a twelve-week trial in 32 treatment-naive
patients chronically infected with the genotype-1 variant of the hepatitis C
virus. The Phase 2a trial was designed to evaluate four doses of Locteron
administered once every two weeks in combination with the antiviral drug
ribavirin. In the SELECT-1 trial, Locteron demonstrated a strong anti-viral
response with 100% of the patients in the two highest dose groups achieving
early virologic response. Viral kinetic modeling of the SELECT-1 results by Eva
Herrmann, Ph.D. of
SELECT-1 Results
Presented Today at EASL Conference
The SELECT-1 results will be presented today at the EASL
conference in a poster titled "Viral Kinetics during Treatment with a
Controlled-Release Recombinant Interferon Alfa-2b in Genotype 1 Chronic
Hepatitis C Patients." Anti-viral results for the SELECT-1 trial were as
follows:
·
The percentage of patients who achieved early
virologic response (EVR), defined as at least a two-log reduction in hepatitis
C virus, was 100% in the 640 and 480 µg dose cohorts and 88% in the 320 µg dose
cohort, compared to 37.5% in the 160 µg dose cohort.
·
A clear dose response was observed in the study,
and viral kinetic modeling by Drs. Herrmann and Zeuzem demonstrated
statistically significant HCV RNA reduction during the entire 12-week treatment
period.
·
Average viral reduction after 12 weeks of
treatment ranged from 4.7 to 4.2 logs for the 640, 480 and 320 µg doses,
compared to 1.8 logs for the lowest dose of 160 µg.
·
Locteron was generally well tolerated at all
doses. There were no serious adverse events in the 160 µg, 320 µg, and 480 µg
cohorts. There was one serious adverse
event in the 640 µg cohort, a case of otitis, or inflammation of the ear, which
resolved.
·
Over 90% of the adverse events that were
experienced were rated as mild.
The SELECT-1 trial also measured certain biomarkers, the
results of which were as follows:
·
Locteron resulted in a dose-dependent reduction
in alanine aminotransferase (ALT), an enzyme released by the liver into the
blood when the liver is damaged.
·
Locteron resulted in a dose-dependent increase in
oligoadenylate synthetase (OAS) and neopterin, markers commonly associated with
the biological effects of interferon alfa.
Locteron Overview
As a controlled-release interferon alfa, Locteron is
designed to improve patient care through a more favorable side-effect profile
compared to existing pegylated interferon products and Albuferon (albumin-fused
interferon), each of which lack a controlled-release mechanism. Locteron
combines BLX-883, a recombinant interferon alfa produced by Biolex in its
patented LEX System(SM), with PolyActive(TM), an advanced controlled-release
drug delivery technology developed by OctoPlus. Locteron is configured to allow
dosing once every two weeks, an improvement in patient convenience compared to
currently marketed pegylated interferon alfa products that require dosing every
week. More importantly, Locteron's controlled-release mechanism results in the
gradual release of interferon alfa to patients over the duration of two weeks.
This controlled-release mechanism is designed to cover inter-dose troughs which
may contribute to the frequency, duration and severity of side effects,
including flu-like symptoms, commonly experienced by patients treated with
currently marketed pegylated interferons and with Albuferon. Biolex is co-developing
Locteron with its partner OctoPlus N.V.
In February 2008, Biolex announced the commencement of
patient dosing in a U.S. Phase 2a clinical trial of Locteron in hepatitis C.
The
Locteron is an investigational therapeutic candidate and has
not been approved for sale by the United States Food and Drug Administration or
by any international regulatory agency.
Pharmasset Adds Two Cohorts to R7128 Hepatitis C Study
-- Two 4-week cohorts
will be enrolled to evaluate R7128 1500mg BID in HCV genotypes 2 and 3 prior
non-responders and R7128 1000mg BID in HCV genotype 1 treatment-naive patients
--
Cohort 3 will study R7128 1000mg BID in treatment-naive patients with HCV genotype 1. This cohort is intended to provide clinical antiviral activity data in support of pharmacokinetic models from earlier studies. Cohort 4 will study R7128 1500mg BID in patients with HCV genotypes 2 and 3 who did not achieve a sustained virologic response (SVR) with previous interferon-based therapy. Cohorts 3 and 4 will both be dosed in combination with Pegasys (peginterferon alfa-2a) plus Copegus (ribavirin).
Patients in Cohorts 3 and 4 are scheduled to begin dosing by the end of May 2008. Preliminary safety and antiviral activity data from the 4-week combination studies are anticipated during the 3rd quarter of 2008. Cohorts 3 and 4 will be conducted in parallel with the global Phase 2b study preparation activities for R7128. The timing of the Phase 2b study is not dependent upon data from Cohorts 3 and 4.
"Our pharmacokinetic modeling of the 500mg and 1500mg cohorts of R7128 in combination with Pegasys plus Copegus suggests that the 1000mg dose could deliver a rapid virologic response (RVR) rate similar to the 1500mg dose," stated Dr. Michelle Berrey, Pharmasset's Chief Medical Officer. "The confirmatory results from this additional cohort will aid us in selecting the appropriate doses to evaluate in the global Phase 2b study that is being planned to evaluate R7128 in triple combination for up to 12 weeks."
"R7128 is equally potent in vitro against HCV genotypes 1, 2, 3 and 4, and we believe it is clinically and commercially important to test R7128 in patients with these HCV genotypes," stated Schaefer Price, Pharmasset's Chief Executive Officer. "Twenty percent of U.S. HCV-infected patients and approximately 30% of European and Latin American HCV-infected patients have genotypes 2 and 3. These patients are currently treated with 24 weeks of pegylated-interferon plus ribavirin, but 20% of this population fails to achieve an SVR. By potentially addressing this unmet medical need in a patient population for whom the standard of care is only 24 weeks, we could possibly design shorter clinical trials that may provide a quicker path to the market for R7128."
Separately, the results of the 4-week Phase 1 clinical trial
evaluating two oral dose levels of R7128 (500mg and 1500mg) in combination with
Pegasys plus Copegus in 50 treatment-naive patients chronically infected with
HCV genotype 1 will be presented at the 43rd Annual Meeting of the European
Association for the Study of the Liver (EASL) in Milan, Italy on Friday, April
25, 2008 at 11:15 AM ET (US) and 5:15 PM CEST (Milan). The scientific presentation will be available
for download in PDF format immediately following the EASL presentation in the
"Events & Presentations" section of the
Please see http://www.clinicaltrials.gov/ or e-mail clinicaltrials@pharmasset.com for more information.
Conference Call
Pharmasset will host a conference call at 1:00 PM ET (US) and 7:00 PM CEST (Milan) on Friday, April 25, 2008 to discuss the addition of two R7128 cohorts, as well as the results of the 4-week combination study of R7128 presented at EASL.
Dial-in Information:
US/Canada Toll-Free callers: +1 (877) 545-1490
US/Canada Toll or International Toll callers: +1 (719)
325-4884
Live audio of the conference call will be simultaneously
broadcast over the internet via a webcast.
To access the live webcast, log on to the "Events &
Presentations" section of the
Please connect to the company's website at least ten minutes prior to the start of the presentation to ensure adequate time for a reliable connection and any software download that may be necessary to listen to the webcast. The archived replay of the webcast will be available on the Pharmasset website for two weeks following the conference call.
About R7128
R7128 is being developed for the treatment of chronic HCV infection. R7128 is a prodrug of PSI-6130, a cytidine nucleoside analog inhibitor of HCV RNA polymerase. A prodrug is a chemically modified form of a molecule designed to enhance the absorption, distribution and metabolic properties of that molecule. Results from an oral single ascending dose study of PSI-6130 in 24 healthy male volunteers showed that PSI-6130 was generally well tolerated with no serious adverse events in doses up to 3000 mg.
R7128 demonstrated potent, dose-dependent antiviral activity across four prior treatment-failure patient cohorts (n=40) receiving 750 mg or 1500 mg administered either once-daily or twice-daily for 14 days as monotherapy. The greatest mean decrease in HCV RNA from baseline was demonstrated in the patient cohort that received 1500 mg twice-daily, the highest dose of R7128 administered in the study. These patients demonstrated a mean 2.7 log10 IU/mL (>99%) decrease in HCV RNA. There was no evidence of the development of viral resistance in any dose cohort after 14 days of dosing.
In a 4-week Phase 1 combination study that was conducted in 50 treatment- naive patients chronically infected with HCV genotype 1, R7128 demonstrated potent short-term antiviral activity and was generally safe and well tolerated. Eighty-five percent (85%) of patients receiving R7128 1500mg twice- daily (BID) with Pegasys plus Copegus for 4 weeks achieved undetectable HCV RNA levels with safety and tolerability comparable to placebo with Pegasys plus Copegus.
Vertex reports promising hepatitis C drug results
By Deena Beasley
LOS ANGELES, April 23 (Reuters) - Vertex Pharmaceuticals Inc
(VRTX.O: Quote, Profile, Research) on Wednesday said early trial results show
that its experimental hepatitis C treatment controlled or eradicated the virus
in more than 80 percent of patients for whom previous treatment had failed.
The ongoing study involves only patients with chronic
hepatitis C who were unable to achieve control of the serious liver disease
with the standard treatment of pegylated interferon and ribavirin.
Vertex said interim results from the open-label trial found
that 49 of 60 patients treated with three-times-a-day telaprevir in combination
with the other two drugs showed a high rate of viral response after four weeks.
"We are shooting for a cure to the disease," said
Kurt Graves, chief commercial officer at Vertex.
The company said the response appears to have been
maintained, with no viral breakthrough, in the 36 patients who have completed 4
weeks of treatment and continued out to 8 weeks and in the 16 patients who have
continued to 12 weeks of treatment.
"While early, these results are very promising. Patients
who have not achieved sustained viral response with prior treatment represent
the largest unmet medical need in hepatitis C," Dr. Fred Poordad, chief of
hepatology at Cedars-Sinai's liver disease center in
He said only 10 percent to 15 percent of patients have their
virus eradicated when re-treated with current therapies.
The trial results were presented in
Hepatitis C is a blood-borne disease that can cause chronic
liver disease, liver cancer and cirrhosis. It affects roughly 170 million
people worldwide.
Side effects of telaprevir
include fatigue, nausea, headache and rash.
Vertex said nine patients dropped out of the trial before 12
weeks, including five whose viral loads did not drop far enough and two who
experienced viral breakthrough. One patient discontinued treatment due to rash
and one discontinued due to inflammation of the chest cavity.
Telaprevir is designed to block HCV protease, an enzyme
essential for the virus to replicate.
Earlier trials in previously-untreated patients found that
the drug eradicated the virus in more than 60 percent of patients -- a rate
about 20 percent higher than that seen with current therapies.
The company also expects to complete late this year
enrollment in a pivotal phase 3 trial of telaprevir in treatment-naive
patients. (Editing by Carol Bishopric)
Pharmasset Presents Results of 4-Week Combination Study of R7128 for the Treatment of Chronic Hepatitis C
- 85% of patients achieve undetectable
HCV RNA levels following 4 weeks of treatment with R7128 1500mg BID with
Pegasys(R) plus Copegus(R) -
- Safety and tolerability comparable to
placebo administered with Pegasys plus Copegus -
- EASL presentation available on
Pharmasset website -
- Conference call scheduled for
PRINCETON, N.J. and MILAN, Italy, April 25
/PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS - News) announces the
results of a 4-week Phase 1 clinical trial evaluating two oral dose levels of
R7128 in combination with Pegasys (pegylated interferon) plus Copegus
(ribavirin) in 50 treatment-naive patients chronically infected with hepatitis
C virus (HCV) genotype 1. R7128, a prodrug of PSI-6130, is a nucleoside
analogue polymerase inhibitor of HCV that is being developed through
Pharmasset's collaboration with Roche. The results of this study were presented
today at the 43rd Annual Meeting of the European Association for the Study of
the Liver (EASL) being held from
In this study, R7128 demonstrated potent short-term
antiviral activity and was generally safe and well tolerated. Eighty-five
percent (85%) of patients receiving R7128 1500mg twice-daily (BID) with Pegasys
plus Copegus for 4 weeks achieved undetectable HCV RNA levels with safety and
tolerability comparable to placebo with Pegasys plus Copegus.
Dr. John McHutchison, professor of medicine at Duke
University Medical Center and a clinical investigator for this study, stated,
"R7128, in combination with Pegasys plus Copegus, has demonstrated Rapid
Virologic Response (RVR) percentages in a 4-week study that are similar to HCV
protease inhibitors and has an encouraging short-term clinical safety profile.
Longer-term studies of R7128 with Pegasys plus Copegus are needed to provide
additional information about its potential to improve sustained virologic
response (SVR) rates for HCV patients."
R7128 4-week
Combination Study Overview
The 4-week Phase 1 combination clinical trial was a multiple
center, observer-blinded, randomized and placebo-controlled study that was
conducted in 50 treatment-naive patients chronically infected with HCV genotype
1. The primary objective was to assess the safety, tolerability and
pharmacokinetics of R7128 in combination with Pegasys plus Copegus. The
secondary objective was to evaluate the change in HCV RNA after 4 weeks of
treatment.
The study investigated two oral dose levels of R7128, 500mg and 1500mg, each administered twice-daily (BID) with once-weekly injections of Pegasys plus Copegus BID. Each cohort of 25 patients was comprised of 20 patients receiving R7128 and 5 patients receiving placebo with Pegasys plus Copegus.
Antiviral Activity Summary
|
|
Placebo + Pegasys plus Copegus (n=10) |
R7128 500mg + Pegasys plus Copegus (n=20) |
R7128 1500mg + Pegasys plus Copegus (n=20) |
|
Mean Decrease in HCV RNA
(log10 IU/mL) at 4 Weeks |
-2.95 |
-3.82 |
-5.12 |
|
Percentage of Patients with
Undetectable HCV RNA (<15 IU/mL) at 4 Weeks (RVR) |
10% |
30% |
85% |
Potent antiviral activity was demonstrated following 4 weeks
of treatment with R7128 1500mg BID with Pegasys plus Copegus. These patients
achieved a mean 5.12 log10 IU/mL decrease in HCV RNA and 85% (17 of 20) had
undetectable levels of HCV RNA (<15 IU/mL), or RVR. Following 4 weeks of
treatment with R7128 500mg BID with Pegasys plus Copegus, patients achieved a
mean 3.82 log10 IU/mL decrease in HCV RNA and 30% (6 of 20) had RVR. Following 4
weeks of treatment with placebo with Pegasys plus Copegus, patients achieved a
mean 2.95 log10 IU/mL decrease in HCV RNA and 10% (1 of 10) had RVR. The
baseline HCV RNA levels for all patients in the study were greater than 6.3
log10 IU/mL and were similar across all study groups.
Safety Summary
Safety and tolerability for the 4-week treatment period were
similar for R7128 with Pegasys plus Copegus compared to placebo with Pegasys
plus Copegus. There were no serious adverse events reported during the 4-week treatment
period, and most of the adverse events reported were of mild to moderate
intensity. The most common adverse events, reported in 15% or greater of
patients in any treatment group during the 4-week treatment period, were
headache, injection site reaction, myalgia, fatigue, chills, rash, nausea,
diarrhea, arthralgia, pyrexia, dizziness, dyspepsia and pruritis. The frequency
and severity of these adverse events, as well as any general body system
observations, were generally similar to clinical experience with the standard
of care for HCV, pegylated interferon plus ribavirin.
Grade 3/4 neutropenia was observed in 30% of the placebo
patients and in 10% to 15% of the R7128 patients in each active dosing cohort.
Grade 3 changes in hemoglobin were observed in 10% of the placebo patients and
in 15% of the R7128 patients. There were no clinically significant changes in
other hepatic, renal, or other safety laboratory parameters, vital signs, or
electrocardiograms.
Overall, there was no clinical evidence of any major organ
toxicities related to R7128. One patient in the active treatment group
discontinued the study during the 4 week treatment period due to
lower-gastrointestinal adverse events. At the time of study discontinuation,
this patient had undetectable HCV RNA. R7128 was generally safe and
well-tolerated when administered for 4 weeks in combination with Pegasus plus
Copegus in patients with HCV genotype 1.
Please see www.clinicaltrials.gov
or e-mail clinicaltrials@pharmasset.com for more information.
Conference Call
Pharmasset will host a conference call at 1:00 PM ET (US)
and 7:00 PM CEST (Milan) on Friday, April 25, 2008 to discuss the R7128 500mg and
1500mg combination study results, as well as the addition of two R7128 cohorts
to the on-going Phase 1 protocol.
Dial-in Information:
US/Canada Toll-Free callers: +1 (877) 545-1490
US/Canada Toll or International Toll callers: +1 (719)
325-4884
Live audio of the conference call will be simultaneously
broadcast over the internet via a webcast. To access the live webcast, log on
to the "Events & Presentations" section of the
Please connect to the company's website at least ten minutes
prior to the start of the presentation to ensure adequate time for a reliable
connection and any software download that may be necessary to listen to the
webcast. The archived replay of the webcast will be available on the Pharmasset
website for two weeks following the conference call.
About R7128
R7128 is being developed for the treatment of chronic HCV
infection. R7128 is a prodrug of PSI-6130, a cytidine nucleoside analog inhibitor
of HCV RNA polymerase. A prodrug is a chemically modified form of a molecule
designed to enhance the absorption, distribution and metabolic properties of
that molecule. Results from an oral single ascending dose study of PSI-6130 in
24 healthy male volunteers showed that PSI-6130 was generally well tolerated
with no serious adverse events in doses up to 3000 mg.
R7128 demonstrated potent, dose-dependent antiviral activity
across four prior treatment-failure patient cohorts (n=40) receiving 750 mg or
1500 mg administered either once-daily or twice-daily for 14 days as
monotherapy. The greatest mean decrease in HCV RNA from baseline was
demonstrated in the patient cohort that received 1500 mg twice-daily, the
highest dose of R7128 administered in the study. These patients demonstrated a
mean 2.7 log10 IU/mL (>99%) decrease in HCV RNA. There was no evidence of
the development of viral resistance in any dose cohort after 14 days of dosing.
Data On Investigational Compounds Being Co-Developed By Tibotec For The Treatment Of Chronic Hepatitis C Presented At EASL 2008
http://www.medicalnewstoday.com
Tibotec BVBA, a global pharmaceutical company dedicated to
the discovery and development of innovative drugs that fight infectious
diseases, is now building a portfolio of novel antiviral therapies to treat
hepatitis C virus (HCV). The investigational protease inhibitors (PI),
telaprevir (VX-950) and TMC435350, are being
co-developed by Tibotec with Vertex and Medivir, respectively. Data on these
compounds will be presented at the 43rd Annual Meeting of the European
Association for the Study of the Liver (EASL) in
According to the World Health Organization, an estimated 170
million persons globally are chronically infected with HCV and three to four
million persons are newly infected each year.[i] Chronic infection with HCV, a
viral infection of the liver, can lead to cirrhosis and liver cancer, and is
the most common cause of liver transplant in Europe.[ii],[iii] The current
standard of care for HCV patients, treatment with pegylated interferon combined
with ribavirin, is effective in thirty to fifty percent of patients with
genotype-1 HCV, the most common type globally.[iv] However, treatment with this
regimen can cause significant side effects and no effective treatment regimen
has been identified for those patients that have failed treatment, sometimes
known as non-responders.[v],[vi] The development of new therapies, particularly
direct antivirals with different modes of action, will allow HCV patients to
undergo a more effective treatment regimen.[vii],[viii]
"Our goal is to develop and bring to market new direct
antivirals for the treatment of hepatitis C that have significant advantages
over the existing standard of care," said Roger Pomerantz, MD, President
of Tibotec Research and Development.
As a global virology leader committed to patient care,
Tibotec uses innovative science and expertise and works with partners to
research, develop, manufacture, and market drugs of unmet need. To date,
Tibotec has brought to market PREZISTATM (darunavir), an antiretroviral
medication for treatment-experienced patients with HIV, and has submitted a
marketing application for its second HIV medication, INTELENCETM (etravirine),
to the European Agency for the Evaluation of Medicinal Products (EMEA). Its
promising pipeline comprises potential treatments for infectious diseases
including HIV, tuberculosis, and HCV.
Telaprevir: Key
Presentations at EASL
Data from four abstracts on telaprevir, which is in phase
III development, will be presented in poster and oral presentations at EASL.
Highlights include early results from VX06-950-107, an ongoing, open-label
study to evaluate the antiviral response to treatment with telaprevir, combined
with pegylated interferon alfa-2a (Peg-IFN) and ribavirin (RBV), in patients
who have failed treatment with Peg-IFN/RBV in any of the three PROVE trials
will be presented as a late-breaker poster. An interim analysis examined a
small subset of patients that included non-responders and relapsers. These are
the first data to be presented on the use of telaprevir in patients who have
previously failed previous Peg-IFN/RBV therapy.
Further results from PROVE-1 (U.S.) and PROVE-2 (
Telaprevir is currently being studied in Phase III clinical
trials in treatment-naďve patients; a Phase III clinical trial in patients that
have previously failed treatment will begin later this year. Tibotec has the
right to develop and commercialise telaprevir in
TMC435350: First
Results in Patients
In addition, data from a placebo controlled, double-blind
Phase I study of TMC435350 will be presented in an oral session on Friday, 25
April. This study examined the safety, tolerability and pharmacokinetics of
TMC435350 in healthy volunteers and also examined antiviral activity of the
drug in a small number of HCV patients who had previously failed treatment.
These are the first data to be presented on the use of TMC435350 in hepatitis C
patients.
Tibotec and Medivir discovered TMC435350 through a drug discovery collaboration. Tibotec has the right to
commercialise the compound throughout the world, excluding the Nordic
countries. A Phase IIa proof-of-concept trial is ongoing in
About Tibotec
Tibotec BVBA, is a pharmaceutical
research and development company. The Company's main research and development
facilities are in
Three Studies Presented at 43rd EASL Strongly Indicate Better Efficacy for PEGASYS in Curing Hepatitis C
Roche today announced that compelling new data from three
studies indicate that chronic hepatitis C patients who received PEGASYS(R) (peginterferon
alfa-2a) plus COPEGUS(R) (ribavirin) had a greater chance of being cured of
their disease than those who received combination therapy with another
pegylated interferon and ribavirin. Results from the studies were presented
this week at the 43rd Annual Meeting of the European Association for the Study
of the Liver (EASL) in
Ascione, et al: A
Prospective, Randomised, Investigator-Initiated Head-to-Head Trial
Results of this independently-conducted study(1)
were presented by Professor Antonio Ascione, Director of the Department of
Gastroenterology Liver Unit at
The results showed that 68.7% of patients on Pegasys achieved a cure, compared to only 54.4% of patients on peginterferon alfa-2b (p=0.008). Furthermore, in genotypes 1 and 4 - the most difficult-to-treat patient group - Pegasys achieved a cure in 54.8% of patients, compared to only 39.8% on peginterferon alfa-2b (p=0.04). Side effects were similar, although there were more withdrawals for side effects in the peginterferon alfa-2b group.
T. Witthoeft, et al:
Hepatitis C Treatment in Real-Life PRACTICE in
Another study presented at EASL, called PRACTICE, analysed the response of 3,470 patients to hepatitis C treatment between 2000 and 2007 in 23 German treatment centres with a high volume of patients(2). Patients were matched by key baseline characteristics, as well as by those who received a similar cumulative ribavirin dose. Among these matched pairs, significantly more patients treated with Pegasys plus Copegus achieved a cure compared to those treated with peginterferon alfa-2b and ribavirin (59.3% vs. 53.0% (p = 0.008)).
Craxi, et al: PROBE
Compares the Pegylated Interferons
PROBE, an observational study, was designed to prospectively
evaluate the efficacy of the pegylated interferons in real-life practice(3). The study enrolled 1,351 patients with genotype
1 virus at 167 treatment centres in
"We are pleased that three separate studies presented at EASL all indicate that Pegasys provided patients with a better chance for a cure. These results will help physicians and patients make an informed choice of treatment for chronic hepatitis C. In fact, in all the major markets, an increasing proportion of physicians and patients have selected Pegasys for their therapy in the last several months," said Dr Ueli Fankhauser, global leader for Pegasys at Roche. "We are committed to further advancing the treatment of hepatitis C. Reflecting Roche's leadership in this area, our comprehensive clinical trials programme aims to optimise treatment with Pegasys and Copegus in the hope of bringing treatment success to even more patients."
Roche Comments on
Schering-Plough "IDEAL" Study
Roche reiterated its position on the Schering-Plough sponsored trial called "IDEAL," results of which were also presented at EASL. Clear biases(4) in the design of this study prevent any direct comparison of the pegylated interferons. These biases include:
- different blinding for the Pegasys arm,
- different ribavirin starting doses,
- a different ribavirin dose reduction protocol, and
- unequal thresholds for the use of erythropoietin-stimulating agents.
Despite these biases, it is interesting to note that significantly more patients in the Pegasys arm had an undetectable viral load while on treatment ("end of treatment" response)(5). This is a promising finding, given that the likelihood for a cure in these patients is even higher when modern treatment principles, such as extending the treatment period beyond 48 weeks, are applied. In addition, the study failed to show a benefit for weight-based dosing of peginterferon alfa-2b (which requires dose adjustments based on a patient's body weight) vs. Pegasys, which is given as a fixed dose regardless of a patient's body weight.
Roche's R1626, First-in-Class Hepatitis C Polymerase Inhibitor, Demonstrates Impressive End-of-Treatment Response in Phase IIa Study
http://www.finanznachrichten.de
- R1626 Also Shows a
High Barrier to the Development of Resistance
Roche's investigational treatment for hepatitis C, R1626, has shown an impressive end-of-treatment response rate when given in combination with PEGASYS(R) (peginterferon alfa-2a) and COPEGUS(R) (ribavirin).
After 4 weeks of treatment with this triple combination, followed by 44 weeks of Pegasys and Copegus, levels of the hepatitis C virus (HCV) were undetectable in 84% of patients infected with genotype 1 virus. This was higher than in patients treated with Pegasys and Copegus alone for the entire 48-week treatment period (65%).(1) These new data were presented in a late-breaker oral session at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL), being held in Milan, Italy.
Discovered and developed at Roche, (News/Aktienkurs) R1626 is a potent polymerase inhibitor which belongs to a new generation of treatments that directly inhibit replication of HCV. It is the most advanced polymerase inhibitor in development.
"These results demonstrate that R1626 holds significant
promise to potentially increase the number of hepatitis C patients who can be
successfully treated. It is particularly interesting that R1626, a polymerase
inhibitor, is demonstrating a higher end-of-treatment response rate than
current HCV protease inhibitors in development, together with a high barrier to
the development of resistance," said Dr David Nelson, Director of
Hepatology and Liver Transplantation at the
Patients in this Phase IIa study will be followed for an additional 24 weeks with no treatment to determine the rate of sustained virological response (SVR), indicating a cure.
Rapid development of R1626 - a Large Phase IIb Study is Now Fully Enrolled
A large Phase IIb study with R1626 was initiated in November 2007 to define the optimal dose of R1626, in combination with Pegasys and Copegus. This Phase IIb trial, called POLI 1, is now fully enrolled with approximately 500 patients.
More About the Phase IIa Study and End-of-Treatment Results
Presented at EASL
The Phase IIa study is a multicenter trial that enrolled 104 patients with genotype 1 HCV, who had not previously received treatment. Its primary endpoint was to evaluate the 4-week efficacy and safety of combining R1626 with Pegasys alone or with Pegasys plus Copegus, in comparison to a current HCV standard of care, Pegasys plus Copegus.
Patients were randomised
into the following treatment groups:
- Group A: R1626 1,500 mg twice a day plus Pegasys 180 mcg weekly for 4 weeks
- Group B: R1626 3,000 mg twice a day plus Pegasys 180 mcg weekly for 4 weeks
- Group C: R1626 1,500 mg twice a day plus Pegasys 180 mcg weekly plus Copegus 1,000/1,200 mg daily for 4 weeks
- Group D (standard of care group): Pegasys 180 mcg weekly plus Copegus 1,000/1,200 mg daily for 4 weeks
Following the 4 weeks of treatment in this study, all patients received Pegasys 180 mcg weekly plus Copegus 1,000/1,200 mg daily for an additional 44 weeks to complete the 48-week trial.
The study found(1):
- Data collected at 4 weeks showed that patients receiving the triple combination (Group C) had a mean decrease in viral load of 5.2 log10 from baseline, indicating a robust and rapid virological response
- At week 48, HCV was undetectable in 84% of patients receiving the triple combination R1626 1,500 mg BID + Pegasys + Copegus, compared with 65% of patients treated with Pegasys and Copegus alone
- A higher incidence of grade 4 neutropaenia was reported in the R1626 treatment arms during the 4-week treatment period; however, after stopping treatment with R1626, absolute neutrophil counts returned to the levels typically seen with patients taking standard of care alone
R1626 - a High
Barrier to the Development of Resistance
In a separate oral presentation at EASL, it was reported that R1626 continues to present a high barrier to the development of viral resistance. Resistance is a serious concern in hepatitis C treatment, as resistant viruses have emerged in patients early on in treatment with protease inhibitors. Resistance to R1626 has not been yet been identified, after either 2 weeks of R1626 monotherapy, or after 4 weeks in patients treated with R1626 in combination therapy.(2)
Vertex Announces Positive Interim
Results with Telaprevir-based . Therapy
in Genotype 1 Chronic Hepatitis C Patients who Failed to Achieve S SVR with a
previous pegylated interferon and ribavirin treatment regimen.
In a late-breaker poster presentation at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL), researchers today will present data from an interim analysis of telaprevir (VX-950) in combination with pegylated interferon and ribavirin in genotype 1 chronic hepatitis C patients who failed to achieve SVR with a previous pegylated interferon and ribavirin treatment regimen.
The interim results are from the 107 study, an ongoing, open-label study which was designed to provide access to telaprevir in patients who met on-treatment criteria for null or partial response, or relapsed after the completion of 48 weeks of pegylated-interferon (peg-IFN) and ribavirin (RBV), in the control arms of the telaprevir Phase 2b PROVE studies.
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) is developing telaprevir in collaboration with Tibotec.
In the interim analysis, patients treated with telaprevir in combination with peg-IFN and RBV demonstrated a high rate of viral response at week 4 (49 of 60 patients achieved HCV RNA <25 IU/mL).
This response appears to have been maintained, with no viral breakthrough observed to date in the 36 patients who have completed 4 weeks of treatment and continued out to 8 weeks and in the 16 of those patients who have continued out to 12 weeks of treatment.
"While early, these results are very promising.
Patients who have not achieved SVR with prior treatment represent the largest unmet medical need in hepatitis C, as typically only 10% to 15% of those re-treated with current therapies achieve sustained virologic responses.
The fact that the most difficult-to-treat patients showed
such a profound early response is very encouraging," said Fred Poordad,
M.D., study author of the PROVE 1 and 107 studies, and Chief of Hepatology at
the
The results will be presented in a late-breaker poster titled, "A Study of Telaprevir (TVR) with Peginterferon alfa-2A (P) and Ribavirin (R) in Subjects with Well-documented Prior P/R Null Response, Non-Response or Relapse: Preliminary Results" starting today.
Interim Data Analysis
Summary - 107 Study
The 107 study results presented at EASL represent an interim analysis for patients who received telaprevir-based therapy.
Patients could enroll in the 107 study if they did not achieve SVR in the control arms of the Phase 2b telaprevir studies - PROVE 1, 2 and 3.
These patients were followed closely in the PROVE studies and can be well-characterized as null responders, partial responders or relapsers to standard treatment.
Null responders are defined as patients who had less than a 1 log(10) decrease in HCV RNA at week four or less than a 2 log(10) decrease in HCV RNA at week 12.
Partial responders are defined as patients who had a greater than 2 log(10) decrease in HCV RNA at week 12, but had detectable HCV RNA at week 24.
Relapsers are defined as patients who had undetectable HCV RNA at the end of treatment but reverted to detectable levels of HCV RNA after stopping treatment.
The results include data from all enrolled patients in study 107 who received at least one dose of telaprevir-based treatment and who completed the week 4 assessment.
At the time of analysis, 72 patients had received at least one dose of study drug and 60 patients had completed week 4.
Patients continued treatment at week 4 and 12 if they did not meet the stopping rule criteria, defined as HCV RNA >25 IU/mL (Roche Taqman assay, version 2.0) at either of those time points.
Nine patients discontinued all study treatment prior to week 12, including 5 patients who met the week 4 stopping rule, 2 patients who experienced breakthrough (both at week 2), 1 patient who discontinued due to an adverse event, and 1 patient who discontinued due to an adverse event and also met the week 4 stopping rule.
A high proportion of patients, regardless of the patient s degree of non-response to prior treatment, achieved HCV RNA <25 IU/mL at week four of treatment, and available data as of the interim analysis indicate that in patients who continued past week four, response has been maintained through week 12.
Week 4, 8 and 12 on-treatment antiviral responses are summarized in the table “-0- *T Prior Virologic Response in Interim HCV RNA Results in Patients Phase 2 control arm Reaching Week 4, 8 and 12 Assessments studies”
Interim Results From Boceprevir Phase II Study In Genotype 1 Treatment-Naive Hepatitis C Patients Presented At EASL
http://www.medicalnewstoday.com
Schering-Plough Corporation (NYSE: SGP) reported that results from a planned interim analysis of an ongoing Phase II study of boceprevir, its investigational oral hepatitis C protease inhibitor, in 595 treatment-naive patients with chronic hepatitis C virus (HCV) genotype 1 were presented at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL). The ongoing study evaluates boceprevir in 28-week and 48-week treatment regimens.
In a 28-week treatment regimen in which patients received 4 weeks of PEGINTRON(TM) (peginterferon alfa-2b) and REBETOL(R) (ribavirin, USP) prior to the addition of boceprevir (800 mg TID), the rate of sustained virological response at 12 weeks after the end of treatment (SVR 12) was 57 percent (ITT).(1-3) Importantly, this treatment regimen provided an indication of early predictability of response, with patients who had undetectable virus (HCV-RNA) in plasma after 4 weeks of boceprevir treatment achieving an SVR 12 rate of 86 percent.
"These interim results are very encouraging, especially
given the response seen with a shorter course of therapy in a
difficult-to-treat patient population," said principal investigator Paul
Kwo, M.D., associate professor of medicine and medical director, liver
transplantation, Department of Medicine, Division of
Gastroenterology/Hepatology, Indiana University School of Medicine,
Overall, 77 percent of the 595 patients in the study were
enrolled in the
In the ongoing study, known as HCV SPRINT-1 (HCV Serine Protease Inhibitor Therapy-1), boceprevir (800 mg TID) is being evaluated in three treatment regimens: 4 weeks of PEGINTRON (1.5 mcg/kg once weekly) and REBETOL (800-1400 mg daily based on patient weight) therapy followed by the addition of boceprevir to the combination for 24 or 44 weeks (totaling 28 or 48 weeks of treatment); boceprevir in combination with PEGINTRON and REBETOL at the doses described above for 28 or 48 weeks (triple combination); and boceprevir in combination with PEGINTRON and low-dose REBETOL (400-1000 mg daily) for 48 weeks, compared to a control of PEGINTRON (1.5 mcg/kg once weekly) and REBETOL (800-1400 mg daily based on patient weight) alone for 48 weeks (an approved treatment regimen). The primary endpoint of the study is sustained virologic response after 24 weeks of follow up.
During a late-breaker oral presentation at EASL, Dr. Kwo presented interim results for the two 28-week boceprevir arms of the study. For patients receiving 4 weeks of PEGINTRON and REBETOL therapy prior to the addition of boceprevir, SVR 12 was 57 percent (59/103), compared to 55 percent (59/107) for patients in the boceprevir triple combination arm. For patients in these two boceprevir arms who had undetectable virus (HCV-RNA) after 4 weeks of boceprevir treatment (RVR), the SVR 12 rates were 86 percent (53/62) and 74 percent (31/42), respectively. SVR 12 rates are not yet available for patients in the 48-week boceprevir arms or the 48-week control arm, as treatment of these patients is ongoing.
Safety data from the study showed that the most common adverse events reported in the boceprevir arms were fatigue, anemia, nausea and headache. No increase in skin adverse events (rash or pruritus) beyond what was seen in the PEGINTRON and REBETOL control arm was observed. Treatment discontinuations due to adverse events were between 11 and 15 percent for patients in the boceprevir arms, compared to 8 percent for the control arm.
Early response rates at week 4 (RVR) and week 12 (EVR) of boceprevir treatment were increased for patients who received 4 weeks of PEGINTRON and REBETOL therapy prior to the administration of boceprevir (62 and 79 percent, respectively), compared to patients in the triple combination (38 and 69 percent) and control (8 and 34 percent) arms, respectively. In the 28-week boceprevir arms, these patients also had a reduction in viral breakthrough compared to patients in the triple combination arm (4 vs. 7 percent, respectively).
"The results seen with this novel treatment paradigm will influence the design of our future clinical studies, as we plan to consider RVR at week 4 of boceprevir treatment as the criterion for determining which patients can receive a shorter course of boceprevir therapy and which patients should continue treatment for 48 weeks," said Robert J. Spiegel, M.D., chief medical officer and senior vice president, Schering-Plough Research Institute. "Additionally, this strategy has the potential to reduce the likelihood of the development of resistance by identifying patients who are responders to interferon and ribavirin prior to their receiving a protease inhibitor."
The rationale for this novel treatment regimen is based on the fact that both PEGINTRON and REBETOL reach steady-state concentrations by week 4, so patients have the protease inhibitor added at a time when the backbone drug levels have been optimized. In addition, the patient's immune system will have been activated and primed by PEGINTRON at the time that boceprevir is added to the regimen. This approach may minimize the period of time when there is a "functional monotherapy" with a direct antiviral, potentially reducing the likelihood for the development of resistance.
The HCV SPRINT-1 study is currently ongoing at sites across
the
Gilead
Announces 72-Week Data From Two Pivotal Phase III
Studies Evaluating Viread(R) for the Treatment of Chronic Hepatitis B
Resistance surveillance through week 72 did not detect any tenofovir-associated mutations.
Two patients exhibited loss of viral response as defined by study investigators with documented non-adherence and were evaluated via genotypic analysis.
Neither developed mutations associated with Viread resistance.
Study 103 Study 103 is a multi-center, randomized, double-blind Phase III clinical trial evaluating the efficacy, safety and tolerability of Viread among treatment-naive patients with HBeAg-positive chronic hepatitis B.
Two hundred sixty-six patients were originally randomized in a 2:1 ratio to receive either Viread (300 mg once daily; n=176) or Hepsera (10 mg once daily; n=90).
Baseline characteristics were similar between patients in both study arms.
As with Study 102, after the completion of 48 weeks of randomized blinded therapy, all eligible patients were offered open-label Viread monotherapy.
At week 72, 79 percent of patients who were originally randomized to receive Viread had a virologic response below 400 copies/mL.
Among Hepsera-treated patients who switched to Viread after Week 48, 76 percent achieved HBV DNA below 400 copies/mL by week 72.
Through week 72, viral suppression was maintained among all patients who switched to Viread and who were previously virologically controlled with Hepsera (n=12).
Additionally, rapid viral suppression to less than 400 copies/mL was achieved by week 72 in 78 percent of viremic Hepsera-treated patients who switched to Viread after week 48.
At week 72, normal ALT levels were observed in 77 percent of patients who were originally randomized to receive Viread and 61 percent of Hepsera-treated patients who switched to Viread.
Among patients for whom seroconversion data was available through week 64, 26 percent of patients who were originally randomized to receive Viread "e" antigen seroconverted, compared to 21 percent of Hepsera-treated patients who switched to Viread.
Seroconversion is defined as both the disappearance of the hepatitis B "e" antigen (HBe-antigen negative), a marker of HBV replication, and the appearance of antibodies specific for this antigen (HBe-antibody positive).
In addition, 5 percent of patients who were originally randomized to receive Viread compared to zero percent of Hepsera-treated patients who switched to Viread after week 48 experienced "s" antigen (HBsAg) loss (p=0.004), which can indicate that a patient has cleared chronic hepatitis B infection.
As with Study 102, Viread was generally well tolerated.
At week 72, treatment-related serious adverse events occurred in 4 percent of patients who were originally randomized to receive Viread and 7 percent of Hepsera-treated patients.
The incidence of Grade 4 laboratory abnormalities was comparable in each arm (12 percent versus 11 percent).
Grade 3 laboratory abnormalities, excluding ALT elevations, were 18 and 10 percent, respectively.
Grade 3 ALT elevations were 15 and 10 percent, respectively, in the Viread and Hepsera arms.
No patient had a confirmed creatinine clearance of less than 50 mL/minute.
The most common adverse reactions among patients receiving Viread for chronic hepatitis B in Studies 102 and 103 were headache, diarrhea, vomiting, abdominal pain, nausea, abdominal distension, flatulence, ALT increase and fatigue.
In terms of resistance surveillance, between weeks 48 and 72 no patients experienced a loss of virologic response.
Additional Oral Presentations at EASL Three additional oral presentations, one of which features the first data to be presented from Study 106, will be highlighted at EASL.
Study 106 is an ongoing, randomized, double-blind Phase II study of individuals with chronic hepatitis B infection randomized in a 1:1 ratio
Clinical Update - Debio 025 in Hepatitis C
Presentation of Phase
IIa Efficacy Results
The double-blind, placebo-controlled study investigated different dose regimens of Debio 025 in combination with alpha-2a Peg-IFN 180 Mug/week in treatment naive chronic HCV mono-infected patients. Ninety patients were randomised to receive either of the following treatment regimens during 29 days: Peg-IFN with placebo; Peg-IFN with Debio 025 200 mg/day; Peg-IFN with Debio 025 600 mg/day; Peg-IFN with Debio 025 1000 mg/day; and Debio 025 1000 mg/day.
In patients with genotypes 1 and 4, at day 29, the HCV-RNA reduction was -4.6 log10 IU/mL in the Peg-IFN with Debio 025 600 mg/day arm, and -4.8 log10 IU/mL in the Debio 025 1000 mg/day arm. This was significantly different (p< 0.05) from the Peg-IFN with placebo, as well as the Debio 025 1000 mg/day monotherapy arms, in which the reduction in viral load was respectively -2.49 and -2.20. In these two arms, at day 29, the proportion of subjects with undetectable viral load was 25%. This number increased to 66% in the Peg-IFN with Debio 025 1000 mg/day group.
"To obtain these exciting results after an administration period of only one month is promising and demonstrates that Debio 025 will be a breakthrough in the treatment of HCV infections," said Kamel Besseghir, CEO of Debiopharm S.A. "This unique mechanism of action is the first alternative treatment to classic HCV therapies."
Debio 025
Debio 025 is a synthetic first-in-class Cyp inhibitor, being tested in humans as a potential anti-HCV drug. Debio 025 binds strongly to Cyp, host cell proteins thought to confer a replication advantage to HCV. Its potent inhibitory activity on the HCV replication was shown in preclinical studies.
Previous results of a phase Ib study demonstrate that Debio 025 monotherapy for 15 days induced a strong anti-HCV effect (3.6 log10 reduction) in HIV-1/HCV co-infected patients. (Hepatology, Vol. 47, No 3, 2008, Flisiak et al. "The Cyclophilin Inhibitor Debio-025 Shows Potent Anti-Hepatitis C Effect in Patients Coinfected with Hepatitis C and Human Immunodeficiency Virus)."
About Debiopharm
Group
Debiopharm Group is a global biopharmaceutical development specialist that in-licenses promising biologics and small molecule drug candidates. Debiopharm develops its products for global registration and maximum commercial potential for out-licensing to pharmaceutical partners for sales and marketing. Debiopharm independently funds the worldwide development of all of its products while providing expertise in pre-clinical and clinical trials, manufacturing, drug delivery and formulation, and regulatory affairs.
Founded in 1979 and headquartered in
For more information on Debiopharm Group, please visit: http://www.debiopharm.com.
Baraclude (Entecavir) Treatment Resulted In Greater Viral Load Suppression Compared to Adefovir at 96 Weeks In Antiviral-Naive Adult Chronic Hepatitis B E-Antigen Positive Patients
MILAN, Italy, April 26, 2008 /PRNewswire-FirstCall/ --
Bristol-Myers Squibb Company today announced new data from the E.A.R.L.Y. study
(ETV-079), in which treatment of antiviral-naive adult chronic hepatitis B
patients with Baraclude(R) (entecavir) resulted in greater long-term viral load
reduction than adefovir at 96 weeks -- consistent with earlier 12-week results
(primary endpoint). Suppression of viral load to undetectable levels is a
measure of antiviral treatment response and is an important goal of chronic
hepatitis B treatment. These data were presented today in
The E.A.R.L.Y. study is an open-label, randomized, viral kinetics study of 69 antiviral-naive chronic hepatitis B e-antigen (HBeAg) positive patients, comparing the antiviral activity of BARACLUDE and adefovir. All patients in this study had a high viral load at study entry.(1) Of the 49 patients who remained in the study at 96 weeks, 79 percent (n=23/29) of BARACLUDE-treated patients and 50 percent (n=10/20) of adefovir-treated patients achieved undetectable viral load.(2) The mean reduction in viral load from baseline in patients treated with BARACLUDE was -7.82 log(10) copies/mL and was -5.96 log(10) copies/mL in patients treated with adefovir at week 96.
"BARACLUDE maintains considerable antiviral efficacy
through two years of treatment in this analysis," said Nancy Leung, M.D.,
of the
The safety profile was comparable between the treatment groups through 96 weeks. Three percent of patients receiving BARACLUDE(R) (entecavir) (n=1) and 12 percent of patients receiving adefovir (n=5) experienced a serious adverse event. No deaths were observed in either treatment group. The most common adverse events occurring in greater than 10 percent of patients in either treatment group were headache, nasopharyngitis, upper respiratory tract infection, influenza, pyrexia, urinary tract infection, cough, back pain, and diarrhea.
Data Results
By week 96, 22 of the 69 enrolled patients had discontinued the study. Of these, two patients receiving adefovir discontinued due to investigator-determined lack of treatment efficacy between the beginning of year two dosing and the 96-week analysis. The 96-week data reported below represent the results of the 49 patients who entered year two dosing (29 BARACLUDE-treated patients and 20 adefovir-treated patients), using the non-completer = failure (NC=F) method of analysis.
Week 96
· BARACLUDE-treated patients achieved a mean change in viral load of -7.82 log(10) copies/mL from baseline, and adefovir-treated patients achieved a mean change of -5.96 log(10) copies/mL.
· 79 percent (n=23/29) of BARACLUDE-treated patients and 50 percent (n=10/20) of adefovir-treated patients had undetectable viral load (HBV DNA less than 300 copies/mL, measured by the polymerase chain reaction or PCR assay).
· No BARACLUDE-treated patient (n=0/29) and 35 percent (n=7/20) of adefovir-treated patients had viral load greater than or equal to 10^5 copies/mL.
· 97 percent (n=28/29) of BARACLUDE patients achieved ALT normalization (ALT of less than or equal one time the upper limit of normal) compared with 85 percent (n=17/20) of adefovir-treated patients.