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HCV ADVOCATE WEEKLY NEWS REVIEW: A Review of HCV, HBV and HIV/HCV Coinfection Related News and Highlights

Week Ending: May 1^st, 2004

Alan Franciscus
Editor-in-Chief

In This Issue:

• EASL: Small, Unrandomized Study Compares Pegasys to PegIntron
• Third Wave Technologies, Inc. (TWTI) Launches Invader HCV Genotyping Reagents At Clinical Virology Symposium
• Bristol to Seek OKs for Arthritis, Hepatitis Drugs
• Acute Renal Failure After Transarterial Chemoembolization
• Short-Term Interferon-alpha Therapy for Acute Hepatitis C
• New Liver Cancer Treatment Targets Tumors
•Summerall Says He's Feeling Better with New Liver
• URGENT: Hepatitis C – Call To Action



April 26th, 2004

Small, Unrandomized Study Compares Pegasys to PegIntron
Jules Levin
Source: www.natap.com

There have been several news reports in Reuters and other news services reporting on a study comparing Pegasys to PegIntron, leading readers to ask questions about this study and perhaps not understanding the study results. I was at EASL and here is a report on this study. You can read my EASL reports on other interesting studies from EASL including new drugs for HCV.

At the EASL liver conference in Berlin, Italian researchers (Chemello et al) reported results in a poster of a comparison between PegIntron and Pegasys. The study is a small trial in which only 11 patients taking Pegasys were analyzed. The study is not randomized but is a report on consecutive patients seen in the clinic.

The patients receiving Pegasys appear to have more advanced liver disease making it more difficult to compare responses for genotype 1 patients between the two drugs without identifying how many patients on each drug had early or later disease. The study reported end of treatment responses for patients but not sustained response rates, presumably because they don't have SVR data yet.

This study is not related to the IDEAL Study, which is a trial sponsored by Schering Plough and compares Pegasys to PegIntron. The IDEAL Study is a large trial that is just starting and will take several years to be completed.

The poster from the conference said:

75 consecutive (not randomized) naive patients with biopsy proven chronic hepatitis C received:

• 180 mg/once weekly of PEG-IFN alfa-2a (Pegasys)
or
• 1.5 mg/kg/once weekly of PEG-IFN alfa-2b (PegIntron)

Both in combination with 15 mg/kg/daily of ribavirin (Rebetol).

Baseline characteristics between the groups were comparable. HCV-RNA levels were tested by qualitative PCR and quantitative bDNA in all patients at weeks 4, 12, 24 during therapy and at end of therapy (EOT).

Mean body weight:

• 78.8 kg (173 lbs) for patients receiving Pegasys and,
• 73.7 kg (162 lbs) for patients receiving PegIntron.

Mean BMI:

• 26.3 for Pegasys recipients and,
• 24.5 for PegIntron recipients.

Mean ALT:

• 200 U/L for Pegasys recipients and,
• 180 U/L for PegIntron recipients.

These differences don't appear to be very significant. These differences are important, but patients receiving Pegasys appear to have more advanced liver disease

• Fibrosis stage (Ishak)
  o Less fibrosis:
     • F1/F2/F3 0/6/5- (52%) for Pegasys patients vs.
     • F1/F2/F3 3/14/24 (79%) for PegIntron patients;
  o Later stage fibrosis:
     • F4/F5/F6- 6/4/2 (48%) for Pegasys patients vs.
     • F4/F5/F6- 7/1/2 (20%) for PegIntron patients.

RESULTS
The study authors reported the undetectable viral load at end of treatment for 75 patients initially in the study:

• genotype 1 (6 pts) or genotype 4 (11 pts)--(55%) receiving Pegasys + RBV and,
• genotype 1 (21 pts) or genotype 4 (15)---(75%) receiving PegIntron + RBV.

The study authors did not report sustained viral response rates.

For genotype 2/3 patients, the end of treatment response rates:

• 12/12 (100%) receiving Pegasys/RBV and,
• 22/24 (92%) receiving PegIntron/RBV.

For patients with less Fibrosis, the end of treatment response rates:

• (F1-F3) 8/11 (73%) receiving Pegasys/RBV and,
• (F1-F3) 36/41 (88%) receiving PegIntron had undetectable viral load at the end of treatment.

For patients with later stage fibrosis, the end of treatment response rates:

• (F4-F6), 10/12 (83%) receiving Pegasys/RBV and
• (F4-F6), 6/10 (60%) receiving PegIntron/RBV had undetectable viral load.

Thus, the authors concluded Pegasys/RBV performed worse in genotype 1 and better in more advanced liver disease.

As well, the authors claimed PegIntron performed better in the first 4 weeks of therapy based on:

• 3/11 patients in early fibrosis receiving Pegasys/RBV being HCV negative and,
• 21/41 receiving PegIntron/RBV being HCV negative;
• Genotype 1 patients who had negative HCV RNA at week 4:
   o 1/11 receiving Pegasys/RBV and,
   o 9/28 receiving PegIntron/RBV

To support this claim 7/12 (58%) receiving Pegasys/RBV and 16/24 (67%) receiving PegIntron/RBV who had genotype 2/3 had negative HCV RNA at week 4.

In summary, several points need to be considered when interpreting the study results:

• The number of patients receiving Pegasys is small;
• The study is not randomized;
• The Pegasys patients had more advanced disease which complicates interpretation of the results for genotype 1 patients and,
• End of treatment responses were reported but not sustained viral responses.

This study is not related to the IDEAL Study.

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Third Wave Technologies, Inc. (TWTI) Launches Invader HCV Genotyping Reagents At Clinical Virology Symposium
Source: PRNewswire

MADISON, Wis., -- Third Wave Technologies Inc. today announced the launch of its Invader(R) Hepatitis C Virus (HCV) genotyping reagents at the 20th Annual Clinical Virology Symposium in Clearwater Beach, Fla. In addition, scientists from the Cleveland Clinic Foundation and Mayo Clinic are presenting data from separate collaborative studies regarding Third Wave's Invader(R) HCV genotyping reagents at this meeting. These study results detail the Invader(R) platform's ability to provide faster and more accurate results when compared to other commercially available HCV genotyping methods and technologies. The study abstracts and the posters that are being presented at the symposium are available in PDF format at http://www.twt.com/pressreleases/2004
/April_26_2004.html.

The Invader(R) HCV genotyping product, based on the company's proprietary Invader(R) technology platform, enables clinical laboratories to develop assays that identify all six genotypes of the HCV virus, a major predictor of disease progression and response to HCV treatment. Viral pathogens such as HCV have a number of specific genetic variations, known as genotypes. While all of these strains are grouped into the larger HCV category, the identification of the specific genotype of a virus is essential to maximizing treatment and disease management. Once the correct genetic make-up of the virus is identified, an appropriate therapeutic course of action can be specifically tailored.

The HCV genotyping market in the United States and Europe is currently estimated to be more than $50 million and is growing rapidly. Third Wave's reagents incorporate all of the performance benefits associated with the Invader(R) technology platform. Use of the Invader(R) platform in manual assay setups provides results faster than other commercially available technologies, but more importantly, the high-throughput and ease-of-use advantages of the company's proprietary Invader(R) platform enable laboratories to automate the HCV genotyping process easily, reducing hands-on time, while decreasing the time to result.

"The Invader(R) HCV genotyping reagents are just the latest innovation to emerge from our robust pipeline," said John Puisis, president and chief operating officer of Third Wave. "This product provides us with a superior molecular solution for entry into an additional market segment. As we continue to accelerate high-value products from pipeline to market, we are further establishing our position in the molecular diagnostic industry."

About HCV
Hepatitis C virus (HVC) is a positive, single-stranded RNA virus that is a member of the Flaviviridae family. Almost 4 million Americans, or 1.8 percent of the U.S. population and 170 million individuals worldwide, are anti-HCV antibody-positive, indicating ongoing or previous infection with the virus. At least 75 percent of patients with acute hepatitis C ultimately develop chronic infection, and most of those patients have accompanying chronic liver disease. HCV is the leading cause of chronic liver disease in the United States and accounts for approximately 15 percent of acute viral hepatitis cases and up to 50 percent of cases of cirrhosis, end-stage liver disease and liver cancer. HCV infection causes an estimated 10,000 to 12,000 deaths annually in the United States.

About Third Wave Technologies
Third Wave Technologies is a leader in the development and marketing of molecular diagnostics for a variety of DNA and RNA analysis applications, providing physicians and researchers with superior tools to diagnose and treat disease. Third Wave's Invader(R) technology provides the company's customers with exceptional accuracy, scalability and ease of use. The company offers a number of clinical products based on its Invader(R) technology for genetic testing related to multiple disease areas. For more information about Third Wave and its products, please visit the company's website at http://www.twt.com/.

All statements in this news release that are not historical are forward-looking statements within the meaning of the Securities Exchange Act of 1934 as amended. Such forward-looking statements are subject to factors that could cause actual results to differ materially for Third Wave from those projected. Those factors include risks and uncertainties relating to technological approaches of Third Wave and its competitors, product development, manufacturing, market acceptance, cost and pricing of Third Wave products, dependence on collaborative partners and commercial customers, successful performance under collaborative and commercial agreements, competition, the strength of the Third Wave intellectual property, the intellectual property of others and other risk factors identified in the documents Third Wave has filed, or will file, with the Securities and Exchange Commission. Copies of the Third Wave filings with the SEC may be obtained from the SEC Internet site at http://www.sec.gov/. Third Wave expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Third Wave's expectations with regard thereto or any change in events, conditions, or circumstances on which any such statements are based. Third Wave Technologies, Invader and the Third Wave logo are trademarks of Third Wave Technologies, Inc.

Third Wave Technologies Inc.
CONTACT: Rod Hise of Third Wave Technologies, +1-608-663-4010,rhise@twt.com; or Investors: Stephanie Diaz, +1-415-885-2298,sdiaz@vidaLLC.com, or Media: Tim Brons, +1-646-319-8981, tbrons@vidaLLC.com, of Vida, LLC, for Third Wave Technologies Inc.

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April 28th, 2004


Bristol to Seek OKs for Arthritis, Hepatitis Drugs
Source: Reuters

NEW YORK--- Bristol-Myers Squibb Co. (BMY.N: Quote, Profile, Research) , which is counting on new medicines to revive its flagging earnings, on Wednesday said it expects to seek U.S. marketing approvals this year for experimental drugs for rheumatoid arthritis and hepatitis B.

The New York-based drugmaker said it plans by autumn to seek approval for Entecavir, its experimental drug for hepatitis B, an infectious disease that attacks the liver.

Company officials told analysts in a conference call they plan to seek approval before year's end for CTLA41G, a once-monthly injectable treatment for rheumatoid arthritis.

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Acute Renal Failure After Transarterial Chemoembolization
Source: www.gastrohep.com

Doctors, in the latest issue of Alimentary Pharmacology and Therapeutics, find that acute renal failure after transarterial chemoembolization for hepatocellular carcinoma appears to be dose-related.

Transarterial chemoembolization is effective for hepatocellular carcinoma.

However, acute renal failure may occur after transarterial chemoembolization due to the radiocontrast agent.

In this study, doctors from Taiwan investigated the incidence, risk factors and outcome of acute renal failure after transarterial chemoembolization.

Acute renal failure developed in 24% of patients.

The team analyzed 235 hepatocellular carcinoma patients who underwent 843 transarterial chemoembolization treatment sessions.

The team found that the estimated risk of developing acute renal failure was 7% in each treatment session.

The team compared the episodes of transarterial chemoembolization with and without acute renal failure. They found that Child-Pugh class B (OR 2.6) and treatment session (OR 1.3) were independent risk factors of acute renal failure.

Overall, 27 patients had prolonged renal function impairment.

Multivariate analysis found that Child-Pugh class B (OR 4.3) and diabetes mellitus (OR 5.2) were linked with prolonged acute renal failure. This independently predicted a decreased survival (RR 2.3).

Dr Huo's team concluded, "Acute renal failure after transarterial chemoembolization appears to be dose-related and is associated with the severity of cirrhosis".

"Patients with diabetes mellitus or Child-Pugh class B more frequently develop prolonged acute renal failure, which in turn is a poor prognostic predictor".

Aliment Pharmacol Ther 2004; 19(9): 999-1007

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Short-Term Interferon-alpha Therapy for Acute Hepatitis C
Source: www.gastrohep.com

Short-term interferon-alpha in patients with acute hepatitis C is satisfactory if initiated at an early stage of the disease, find researchers in the latest issue of Hepatology.

Acute hepatitis C often progresses to chronic infection.

In this study, researchers from Japan assessed whether short-term therapy with interferon (IFN) during acute hepatitis C was effective in preventing the development of chronic hepatitis.

The team randomized 30 patients with acute hepatitis C into 1 of 2 treatment groups.

In the early-intervention group IFN therapy was initiated 8 weeks after the onset of acute hepatitis. In the late-intervention group, patients underwent a year of observation before therapy was initiated.

The short-term therapy consisted of natural IFN-alpha (6 million units) administered each day for 4 weeks.

Any signs of recrudescence of disease were immediately followed by interval IFN therapy (3 times weekly for 20 weeks).

The team found that short-term therapy was associated with a sustained virological response in 87% of the early-intervention group and 40% of the late-intervention group.

In addition, follow-up treatment was associated with a sustained virological response 100% of the remaining patients in the early-intervention group and 53% of the late-intervention group.

Dr Hideyuki Nomura and colleagues concluded, "Short-term (4 weeks) IFN treatment of patients with acute hepatitis C may be associated with satisfactory results, if initiated at an early stage of the disease".

Hepatology 2004; 39: 1213-19

April 29th, 2004

THURSDAY, April 29 (HealthDayNews) -- A new interventional radiology treatment for liver cancer that delivers radiation directly to the tumor is safe even in patients with compromised liver blood flow.

That's the conclusion of a study in the April issue of the Journal of Vascular and Interventional Radiology.

The radiation is delivered using a technique called embolization, a well-established procedure designed to block a tumor's blood supply, causing the tumor to shrink.

When performing embolization, an interventional radiologist inserts a catheter into the fermoral artery through a tiny incision in the groin. The catheter is guided through the artery to its target.

Through the catheter, tiny particles called microspheres (about the size of grains of sand) are released into the blood vessels feeding the liver tumor. The microspheres block the flow of blood to the tumor.

This new treatment combines a radioactive isotope into the microspheres. These isotope-loaded microspheres move to the tumor, without bothering to cause much blockage of blood flow, and deliver the isotopes directly to the tumor.

This in-patient procedure allows for a higher, local dose of radiation to be used on liver tumors without exposing healthy tissues to radiation, the study found.

"This interventional radiology treatment is a particularly elegant way to give patients a cancer treatment that doesn't harm the healthy cells. So they don't feel sick or have many of the side effects that happen with standard cancer treatments," study author Dr. Riad Salem, an interventional radiologist at Northwestern Memorial Hospital in Chicago, said in a prepared statement.

His study included 15 patients who received a total of 29 treatments using this new technique.

More information

The American Cancer Society has more about liver cancer.

SOURCE: Society of Interventional Radiology, news release, April 2004

April 30th, 2004

LOS ANGELES (Reuters) - Legendary sports broadcaster Pat Summerall, less than three weeks after receiving a new liver, is out of the hospital and improving slowly, he said on Friday.

"I feel OK," Summerall told Reuters from Jacksonville, Florida, where he is recovering after the April 10 transplant at a Mayo Clinic-operated facility there. "I get winded, I don't have any stamina."

Summerall, 73, a college football star and professional player before becoming a broadcaster in the early 1960s, was airlifted to Jacksonville from his Texas home as his condition worsened and the urgency for the transplant became clear.

"During that period I thought 'What the heck am I doing? It's inevitable that I'm not going to get a liver, I can't stand to wait much longer,"' Summerall said.

But after a little more than a week of waiting in the Florida hospital, an organ was found and transplanted. Summerall said he had to have a second operation a day later to control excessive bleeding, but since then he has been recovering steadily.

Best known to audiences as a football commentator, Summerall also covered sports like tennis and golf and was popular for his direct delivery and folksy manner.

While Summerall was able to get a liver in time, many are not as fortunate. According to the Organ Procurement and Transplantation Network, more than 84,000 people nationwide are on organ waiting lists, and on average 16 people die each day awaiting a transplant.

A recovering alcoholic with about 12 years of sobriety, Summerall and his family have acknowledged that his illness was a direct result of his drinking.

But his friends have stood by to support him, including broadcasters like his long-time partner John Madden and Jim Nantz, athletes like former Dallas Cowboys star quarterback Troy Aikman and actress Cheryl Ladd. They have helped run Summerall's corporate video production company in his absence.

"Those are the things that make you feel gratified about the friendships you've made over the years," he said.

Summerall is expected to be able to return to the Dallas area in mid-May. But transplant patients often recuperate from their surgery at different speeds, and for Summerall, his recovery has not been as quick as he might like.

"It's a lot slower than I thought it would be," he said.

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URGENT - Hepatitis C – Call To Action
Source: National Hepatitis C Advocacy Council

Dear Friend,

The members of the National Hepatitis C Advocacy Council hope this email finds you healthy and well.

There are two issues of concern that we want you to know about, issues that have the potential to greatly effect the way hepatitis C is being handled and viewed in the U.S.
1. New guidelines from a prominent Health and Human Services agency that fail to support hepatitis C testing in high-risk adults and contradicts existing screening recommendations; and
2. The Hepatitis C Control and Prevention Act [S.1143/HR.3539] needs a big push from HCV+ constituents to get it moving through committee this year.

Please visit www.hepcnetwork.org/events&news.htm now to review the information and take action on one or both issues.

It's VITALLY important that you respond. The Council will have members in D.C. next week. Your timely call, fax, letter or email to your Senator early next week can and will make a difference in the outcome of these meetings!

Best Regards,

Andi Thomas
President, National Hepatitis C Advocacy Council
Executive Director, Hep-C ALERT, Inc., North Miami, FL

About NHCAC
The purpose of the National Hepatitis C Advocacy Council is to educate policy makers, media and funding sources about hepatitis C and increase financial and infrastructure support for the delivery of hepatitis C prevention, health education and patient care services.

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