News Review

Hepatitis C (HCV) patients with difficult-to-treat disease, who do not respond to previous courses of therapy with either conventional interferon or peg-interferon alfa-2b[1] combination therapy, may now have an improved chance to be cured if they are re-treated with PEGASYS(R) plus COPEGUS(R). Two studies to be presented at the American Association for the Study of Liver Diseases meeting in Boston show that PEGASYS combination therapy is effective in non-responders to previous therapy.

Higher dose strategies for patients not responding to previous conventional interferon combination therapy

One study reports that more than one-third of hepatitis C genotype 1 patients who previously failed to respond to conventional interferon plus ribavirin achieved a sustained virological response (SVR) following re-treatment with a 12-week induction dose of PEGASYS.

Seventy-two patients were randomised into one of three arms where they received the standard dose of 180 microg or an increased dose of either 270 or 360 microg PEGASYS weekly for 12 weeks followed by a 180 microg dose of PEGASYS for the remaining 36 weeks. Throughout the trial, patients received either 1000 or 1200 mg of COPEGUS daily. There was a clear dose response with increasing doses of PEGASYS(R) with patients in the 360 microg induction dose arm achieving a 37.5% SVR. This is important as previous studies have reported SVRs of only around 10% in these difficult to treat patients. (i)

"These data show that a higher induction dose may be an effective treatment strategy for patients who are non-responders to previous therapy," said Dr. Moises Diago, Hepatologist at Hospital General Universitario, Valencia, Spain and lead author of the study. "The SVRs that were achieved in this study with PEGASYS and COPEGUS are encouraging and provide patients with a second chance to achieve viral eradication."

The second study suggests that the positive results seen in re-treating conventional interferon non-responders with PEGASYS and COPEGUS may also be achieved in patients not responding to previous peg-interferon alfa-2b combination therapy.

Pilot study provides look at effectiveness of PEGASYS in peginterferon alfa-2b non-responders

Dr. Norman Gitlin from Emory University in Atlanta, Georgia will present the results of a small single centre study examining the SVR that was achieved by giving PEGASYS plus COPEGUS to patients who failed to respond to a course of therapy with peg-interferon alfa-2b and ribavirin. In the 31 patients that Dr. Gitlin and colleague report on, 32% overall achieved an SVR and pre-existing cirrhosis did not preclude a successful response.

The trial studied patients who were not responsive to peg-interferon alfa-2b combination therapy at 12 to 24 weeks, who were then treated with a fixed 180 microg dose of PEGASYS per week and either 1000 or 1200 mg of COPEGUS daily. Cirrhosis was present in 32% of patients enrolled in the trial and 94% of all patients had genotype 1 HCV - the most difficult-to-treat form of the virus.

"Patients who do not respond to the current standards of care have few if any re-treatment options," said Dr. Gitlin. "The medical community has been skeptical of the value of re-treating patients who've already received a pegylated interferon, however, our experience suggests that the combination of PEGASYS and COPEGUS can provide higher SVRs than we've seen previously in this patient population, and that's good news for patients."

"Roche has encouraged physicians around the world to look at strategies that will give patients the best possible outcome," said Ciro Caravaggio, Hepatitis Franchise Leader at Roche. "The interim results of the high induction dose study were a significant factor in the design of our ongoing REPEAT study in peg-interferon alfa-2b non-responders, and Dr. Gitlin's study also gives us an interesting preview of the results we may achieve in REPEAT," he added.

Roche's ongoing commitment to finding solutions for patients who have not responded to earlier therapy

To support the growing patient population that is non-responsive to the earlier pegylated interferon treatment, Roche initiated a year ago the first global trial to study the efficacy of the new generation pegylated interferon combination therapy against the earlier one. This trial is known as REPEAT, which stands for "REtreatment with PEGASYS in pATients not responding to prior peginterferon alfa-2b/ribavirin combination therapy".

The REPEAT study will evaluate the efficacy and safety of the combination of PEGASYS and COPEGUS given for a longer, 72-week period, as well as examining the role of a 12-week induction regimen in this population.

Currently, 106 treatment sites in Belgium, Brazil, Canada, France, Germany, Greece, Italy, Portugal, Spain, Sweden, Switzerland, Turkey, UK and the USA are enrolling 900 patients for this trial and enrollment is expected to be completed by the beginning of next year. To enrol in REPEAT, patients must be diagnosed with chronic hepatitis C and have failed to achieve a response after at least 12 weeks of therapy with standard doses of peg-interferon alfa-2b and ribavirin.

In addition, there are nearly 50 other trials that have begun in 20 countries where PEGASYS and COPEGUS are being studied in patients who have failed to respond to other therapies.

About PEGASYS

PEGASYS, the market leader worldwide in hepatitis C therapy, provides significant benefit over conventional combination interferon therapy in HCV patients of all genotypes. The benefits of PEGASYS are derived from its large 40 kilodalton (KD) branched-chain polyethylene glycol (PEG) construction, which allows for sustained drug levels over the course of a full week. PEGASYS also distributes more readily to the liver (the primary site of infection) than conventional interferon. PEGASYS is the only pegylated interferon available as a ready-to-administer solution. Each weekly subcutaneous injection contains 180microg of pegylated interferon alfa-2a (40KD), which is the approved dose for all patients, regardless of body weight.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world's leading research-intensive healthcare groups. Its core businesses are pharmaceuticals and diagnostics. As a supplier of innovative 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 is number one in the global diagnostics market, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2003, the Pharmaceuticals Division generated 19.8 billion Swiss francs in prescription drug sales, while the Diagnostics Division posted sales of 7.4 billion Swiss francs. Roche employs roughly 65,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai.

All trademarks used or mentioned in this release are legally protected.

(i) Shiffman, ML, et al. Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial Group. Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment. Gastroenterology 2004;126:1015-1023.

[1] PEG-Intron(R)

Roche

Sheila Gies, Roche, +1-973-687-0188 (mobile). Jo Galea, Axon Communications, +44-208-822-6779

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October 31st, 2004

Hepatitis C Diagnoses Rise; Health Cost Concerns Spread
Sheri Hall / The Detroit News
David Coates / The Detroit News

More in Metro Detroit are learning they have virus that causes severe liver damage

ANN ARBOR - More patients with the hepatitis C virus, the leading cause of liver failure in the United States, are turning up in doctors offices across Metro Detroit with liver damage - a phenomenon likely to drive up health care costs over the next decade.

The problem is not that the virus is spreading but that more people are finding out they're infected. The majority of people with hepatitis C - an estimated 4 million nationwide - don't know they have it. An estimated 180,000 Michigan residents are unknowingly infected with the virus, state data shows.

Hepatitis C patients will rack up more than $13 billion in medical bills between 2010 and 2019 in the United States, according to a study published in the American Journal of Public Health.

The number of new patients requiring treatment for hepatitis C at one Ann Arbor clinic more than doubled from 1997 to 2002, according to a study released this weekend. Other Metro Detroit doctors' offices also are reporting more new hepatitis C patients.

"These are doctors, lawyers, teachers - real people in the community who have lived with a potentially serious virus for more than a decade," said Dr. Thomas Shehab.

Shehab, of Huron Gastroenterology Associates of Ann Arbor, conducted the study. "And when you start looking for it, there is a lot of really severe liver damage in these people. They're going to end up on the public rolls."

Symptoms, such as dark urine and fatigue, often don't show up for 15 years. This leaves millions of people who are unaware the virus is silently wrecking havoc on their livers. Nearly half of the 670 patients in Shehab's study suffered from severe liver damage or cirrhosis, irreversible liver scarring.

"All we're seeing right now is the tip of the iceberg," said Dr. Stuart Gordon, head of hepatology at Beaumont Hospital in Royal Oak. "There's really no question they're going to continue to show up for treatment."

The virus is also causing more cases of liver cancer, he said.

Overall, about 20 percent of people with hepatitis C suffer severe liver damage and most will eventually need liver transplants. Nationwide, there are more than 17,000 people awaiting liver transplants. Doctors here perform about 3,500 of the surgeries annually.

"There's just not enough livers to go around," said Dr. Milton Mutchnick, head of gastroenterology at Wayne State University's School of Medicine. "It's really an epidemic here in Detroit."

Mutchnick's practice sees between 15 and 20 new hepatitis C patients a week. That number has held steady for the past several years and he expects it to decrease as more people learn how to prevent the virus from spreading and current hepatitis C patients die.

The hepatitis C virus was discovered in 1989, but the blood test to identify it wasn't available until 1991. The American Red Cross didn't eliminate hepatitis C from the nation's blood supply until 1992.

It's most commonly spread through IV-drug use, health care workers who were accidentally exposed and people who received blood transfusions before 1992. Among the disease's prominent advocates are supermodel Pamela Anderson and country singer Naomi Judd, both infected with the virus.

Because symptoms don't show up for decades, patients often don't get tested for hepatitis C. Doctors sometimes ask during routine check-ups if a patient could have been exposed to the virus. And a small fraction of people find out they have hepatitis C after donating blood.

It was an unexpected letter from the American Red Cross a decade ago that alerted Laurie Martin, a regular blood donor, that she was infected with hepatitis C. The 50-year-old registered nurse is pretty sure she contracted the virus after being stuck with a needle while working.

Martin essentially ignored the virus for about eight years.

"I was never sick, never had any symptoms, nothing," she said. "It didn't really impact me. My life went on like normal."

Then two years ago, she met Shehab, who specializes in treating hepatitis C patients. He took a myriad of tests. A biopsy of her liver showed some scarring, although it was minimal. Martin decided to wait a year and take more tests.

Today, Martin's liver is still healthy and her life is unchanged. She exercises nearly every day, plays golf and recently went on a hiking trip in the Grand Canyon. And she takes extra precautions at work to be sure she doesn't transmit hepatitis C to any patients.

But it's still possible the virus could damage Martin's liver in the future to the extent that a transplant would be required. She's considering undergoing hepatitis C treatments - about six months of weekly shots that will make her feel like she has the flu. The treatments cure patients about half of the time, and Martin has a higher chance of success because of her genetic makeup.

"It there's something I can do to get rid of the disease, I want to try it," she said. "I make an effort to be a healthy person, so I feel I need to try."

What's most important is that patients like Martin are diagnosed so they can take action to prevent liver damage, Shehab said.

"Maybe you change what you're doing so you don't give it to someone else or maybe you change behavior so you don't get worse," he said.

You can reach Sheri Hall at (313) 223-4686 or shall@detnews.com.

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Now, a Drug Combo that Effectively Treats Hepatitis C:

SourceURL:http://athens-olympics-2004.newkerala.com

[Health India]: Washington, Oct 31 : Saint Louis University School of Medicine researchers and six other American research sites have reportedly discovered a drug combo that could effectively prevent or reduce Hepatitis C viral levels better than when taken individually.

According to Dr. Adrian M. Di Bisceglie, a professor of internal medicine at the university's Department of Gastroenterology and Hepatology, using the drugs Peg-Intron(R) and Pegasys together with Ribavirin had better results than when they were taken individually.

Pegasys and Peg-Intron are types of pegylated alpha interferon-- which is a longer lasting version of interferon, a naturally produced substance in the body that triggers the immune system. Combining these drugs with ribavirin enhances their efficacy and is the standard treatment for hepatitis C.

"It looks as though Pegasys is more potent during the early phase of treatment, which is critical for patients with chronic hepatitis C," claimed Di Bisceglie.

"It's critical because if patients are going to respond to treatment, it will happen during the first 12 weeks of care. Eight weeks into this trial, we noticed lower viral levels in patients on the combination of Pegasys and Ribavirin," he added.

This is one of the first head-to-head studies in the United States comparing Pegasys and Peg-Intron when each are combined with equal doses of ribavirin. Pegasys is the most recent form of pegylated alpha interferon approved by the Food and Drug Administration (2002).

Di Bisceglie presented his findings at the 55th annual meeting of the American Association for the Study of Liver Diseases in Boston earlier this week.

He said the ultimate goal of his new therapy was to clear patients of the blood-borne virus or have levels drop so low as to be undetectable.

While the Pegasys results are positive, Di Bisceglie cautioned it is too soon to draw conclusions. The 12-week trial is still under way.

"Studies such as this one give us insight into how these drugs work and it might allow us to design better drugs in the future," said Di Bisceglie, one of the top liver disease experts in the world. (ANI)

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November 1st, 2004

Vertex Hepatitis Drug Dosing to Advance
Associated Press

Biotech company Vertex Pharmaceuticals Inc. reported Monday that it plans to begin enrolling the next phase of early stage clinical trials for its Hepatitis C drug this month after finding no initial safety concerns.

In a Phase Ia dose-escalation study, Vertex found that VX-950 was well-tolerated in healthy individual in doses ranging from 25 milligrams to 1250 milligrams. The company said there were no serious adverse events in the trial and that higher doses of the drug did not appear to increase adverse events.

The Phase Ib part of the trial will enroll healthy volunteers and patients with chronic hepatitis C virus infection. The trial will follow subject on 14-day dosing regimens of the drug.

VX-950 is among a class of antiviral drugs known as protease inhibitors and has been shown to reduce levels of Hepatitis C virus within days in preclinical testing, the company said.

Chronic Hepatitis C virus affects about 2.7 million people in the United States.

Shares of Vertex rose 41 cents, or 3.8 percent, to $11.29 in midday trading on the Nasdaq.

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SciClone's ZADAXIN Shows Promise in Triple Therapy Trial for Hepatitis C Non-Responder Patients; Endpoint Data Presented at World's Largest Meeting of Liver Specialists American Association of the Study of Liver Disease (AASLD)
http://home.businesswire.com/portal

SAN MATEO, Calif.--(BUSINESS WIRE)--Nov. 1, 2004--SciClone Pharmaceuticals, Inc. (Nasdaq:SCLN) today reported that triple therapy of ZADAXIN(R) combined with pegylated interferon and ribavirin in a pilot trial in Mexico showed a sustained virologic response (SVR) in 19% of difficult to treat hepatitis C patients, non-responders infected with the genotype 1 strain of the virus.

"The response rate achieved by this genotype 1 subgroup is more than twice the 9% SVR observed in a separate, unrelated trial treating genotype 1 non-responder patients with pegylated interferon and a similar dose of ribavirin but without ZADAXIN," commented Eduardo B. Martins, M.D., Ph.D. Vice President, Medical Affairs of SciClone Pharmaceuticals, Inc. "We are pleased by the results of this pilot study, particularly considering that a low dose of ribavirin was used and all of the patients are Hispanic, a patient population that is suggested to be less likely to respond to therapy. Although this was a small, uncontrolled pilot trial and reliable conclusions cannot be drawn from comparisons of results of different studies, we are encouraged by these results."

Genotype 1 infected carriers account for 70% of the 2.7 million chronic carriers of the hepatitis C virus (HCV) in the United States. Most genotype 1 patients fail initial therapy of pegylated interferon and ribavirin and become non-responders.

Non-responders to previous hepatitis C therapy are the subjects of SciClone's two U.S. phase 3 clinical trials for ZADAXIN in combination therapy with pegylated interferon. These trials are fully enrolled with over 1,000 patients and SciClone expects to report data in early 2006. As previously announced, SciClone's European partner Sigma-Tau plans to begin enrolling non-responders in a 550-patient phase 3 triple therapy trial using the current standard dose of ribavirin, which is about 20% higher than the dose of ribavirin used in this pilot trial. SciClone's goal for the European trial is to generate data on ZADAXIN's use as part of triple therapy for hepatitis C patients.

About the Triple Therapy Trial

The endpoint data from this pilot clinical trial were presented at the largest meeting of liver specialists in the world, the annual meeting of the American Association of the Study of Liver Disease (AASLD) held in Boston, MA on Saturday, October 30, 2004. The following table summarizes the response rates over the course of the trial:

Summary of Results		Intent-to-Treat	Per Protocol
	Week 48 (1) End of Therapy	Week 72 (1) SVR	Week 72 (1) SVR
All combination therapy non-responders (n=25)	48% (12/25)	16% (4/25)	17% (4/23)
Genotype 1 (n=21)	48% (10/21)	19% (4/21)	21% (4/19)

(1) HCV RNA negative by PCR test

Using an intent-to-treat analysis, 16% (4/25) of all patients and 19% (4/21) of the difficult to treat genotype 1 patients achieved an SVR at the trial endpoint (72 weeks). Using a per protocol analysis which excludes the 2 patients who dropped therapy by week 24 due to adverse side effects from pegylated interferon, 17% (4/23) of all patients and 21% (4/19) of genotype 1 patients achieved an SVR. None of the other four patients, all genotype 2, achieved an SVR.

This small, open label, single-arm pilot trial enrolled 25 Hispanic patients infected with HCV, none of whom had responded to previous treatment of at least 24 weeks of interferon plus ribavirin. Patients received 48 weeks of therapy of a standard dose of ZADAXIN (1.6 mg/twice-weekly), a standard dose of pegylated interferon alfa-2a (180 mcg/week), and a low dose of weight-based ribavirin (800-1,000 mg/day). At the end of 48 weeks of therapy, patients were observed for 24 weeks to determine SVR at week 72, the trial endpoint. During the course of therapy, 44% (11/25) of patients required a dose reduction of pegylated interferon, 28% (7/25) required a dose reduction of ribavirin and none required a dose reduction of ZADAXIN. As in all previous ZADAXIN studies, the safety profile was excellent without significant ZADAXIN related side effects or toxicities.

Background on Hepatitis C Trials

Sigma-Tau, SciClone's European partner, plans a 550-patient, multi-center, double-blinded, placebo-controlled phase 3 clinical trial to determine the potential additive benefit of ZADAXIN to the standard hepatitis C treatment regimen of pegylated interferon and ribavirin in non-responders. Patients will receive 48 weeks of treatment with either ZADAXIN (1.6 mg/twice-weekly) or placebo in addition to a standard dose of pegylated interferon alfa-2a (180 mcg/week) and the current standard dose of ribavirin (1,000-1,200 mg/day). Following treatment, all patients will be followed for an additional 24 weeks to determine SVR.

SciClone's ongoing U.S. phase 3 clinical trials are fully enrolled with over 1,000 patients and are multi-center, randomized, double-blinded studies. Patients are receiving 48 weeks of treatment with either ZADAXIN (1.6 mg/twice-weekly) or placebo in combination with pegylated interferon alfa-2a (180 mcg/week). Following treatment, all patients will be followed for an additional 24 weeks to determine SVR. The company expects to report results from these trials in early 2006.

About SciClone

SciClone Pharmaceuticals is a biopharmaceutical company engaged in the development of therapeutics to treat life-threatening diseases. SciClone's lead product ZADAXIN(R) is currently being evaluated in two phase 3 hepatitis C clinical trials in the United States. ZADAXIN is also being evaluated in other late-stage clinical trials for the treatment of hepatitis B and certain cancers. The company's other principal drug development candidate is SCV-07, which is currently being evaluated in pre-clinical studies for the treatment of viral and other infectious diseases. For more information about SciClone, visit www.sciclone.com.

The information in this press release contains forward-looking statements including the prospective development, commercialization and regulatory approval of ZADAXIN in the U.S. Words such as "expects," "plans," "believe," "may," "will," "anticipated," "intended" and variations of these words or similar expressions are intended to identify forward-looking statements. In addition, any statements that refer to expectations, projections or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. These statements are not guarantees of future performance and are subject to risks, uncertainties and assumptions that are difficult to predict. Therefore, actual results could differ materially and adversely from those expressed in any forward-looking statements as a result of various factors, including the fact that results from studies with a limited group of patients may not be predictive of the results of larger studies, maintenance of the sufficiency and eligibility of the enrolled patient population, the actions and decisions of Sigma-Tau regarding its proposed trial, unexpected adverse results to patients and other events that could prolong the clinical trial or result in unanticipated expense, we may not receive hepatitis C approval for ZADAXIN in the U.S., future actions that may be taken by regulatory agencies, as well as other risks and uncertainties described in SciClone's filings with the Securities and Exchange Commission.

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New Hope for Hepatitis B Sufferers http://www.axcessnews.com
Freddie Mooche

Bristol-Myers Squibb Company may have new hope for hepatitis B sufferers according to two studies conducted by the drug giant.

Nov 1, 2004 (AXcess News) Boston - Bristol-Myers Squibb Company (NYSE: BMY) may have new hope for hepatitis B sufferers according to two studies conducted by the drug giant.

Investigational chronic hepatitis B compound entecavir demonstrated significantly greater improvements in both liver histology and reductions of hepatitis B virus (HBV) DNA levels compared to lamivudine in two studies.

According to data to be presented at the 55th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), investigating both nucleoside-naive, e-antigen-negative (HBeAg-) chronic hepatitis B patients (Study AI463-027) and e-antigen-positive (HBeAg+) chronic hepatitis B patients who had developed resistance to lamivudine (Study AI463- 026) - both studies were multinational, double-blind, Phase III clinical trials.

HBeAg negative chronic hepatitis B is characterized by a progressive course of severe liver damage with a poor long-term prognosis and frequent progression to cirrhosis and liver cancer. After 48 weeks of treatment, 70 percent of patients treated with entecavir demonstrated histologic improvements compared to 61 percent of patients treated with lamivudine.

"In this study, a higher proportion of hepatitis B e-antigen negative patients receiving entecavir experienced improvements in liver histology and viral suppression compared to lamivudine," said Dr. Daniel Shouval, a lead AI463-027 investigator and director of the Hadassah University Hospital's liver unit in Jerusalem, Israel.

Bristol-Myers third quarter profits sagged 16 percent after the loss of key patent protection for some of its products and heavier research and development spending.

For the quarter, Bristol-Myers earned $758 million, or 38 cents a share, compared with $906 million, or 47 cents a share, a year earlier.

Shares of Bristol-Myer closed Friday at $23.43, down 58 cents.

Competitor Schering AG (NYSE: SHR), manufacturer of hepatitis drug Peg-Intron, closed up 33 cents at $64.18. The German-based drug manufacturer reported Thursday Oct. 21 that in the first nine months of 2004 it achieved net sales growth of 6 percent.

Merck & Co. (NYSE: MRK) closed down 26 cents at $31.31. The manufacturer of Vioxx had been plagued by law suits since its recall of that drug but said in statement released last week that it "acted responsibly" in manufacturing the arthritis drug after some of the court documents leaked out.

Pfizer, Inc. (NYSE: PFE) closed up 24 cents at $28.95. Two drugs in the same class as Vioxx made by Pfizer, Celebrex or Bextra, lack direct studies measuring cardiovascular risk. Merck's inability to get it past the FDA could affect the company.

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Dynavax Hepatitis B Vaccine Tops Glaxo's in Phase II (DVAX, GSK)
Aude Lagorce
http://cbs.marketwatch.com

LONDON (CBS.MW) -- Drug developer Dynavax Technologies (DVAX) said that data from a Phase II clinical trial of its prophylactic hepatitis B vaccine showed superior results compared to GlaxoSmithKline's (GSK) Engerix-B vaccine. Dynavax said that four weeks after the first dose, 79 percent of the HBV-ISS treated group had a protective antibody response compared to 12 percent of the Engerix-B recipient group.

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Studies Demonstrate Positive Data in Treatment of Hepatitis C
SourceURL: http://www.eurekalert.org

BOSTON --Data from two ongoing studies testing new approaches for the treatment of chronic hepatitis C will be presented at the annual meeting of the American Association for the Study of Liver Diseases (AASLD) this afternoon.

Presented by 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, the new findings provide researchers with sufficient evidence to demonstrate promising results for hepatitis C patients who have not responded to existing therapies.

A viral infection, hepatitis C is transmitted through exposure to infected blood. The virus, which affects an estimated 4 million individuals nationwide, is able to survive and flourish inside the body by taking up residence in the liver cells, and subsequently using the cells' inner machinery to make more copies of the virus. These in turn, infect other healthy cells.

The standard treatment for hepatitis C is a combination of interferon alfa and ribavirin, which act as anti-viral agents to eradicate the virus. According to Afdhal, the most recent advance in treatment has been the pegylation of interferon, which enables a once- a- week administration of the protein by injection and improves the ability to clear the virus. Combination therapy with pegylated interferon plus ribavirin for 24 to 48 weeks can result in eradication of the virus in about 50 percent of patients, he adds.

"When the hepatitis C virus doesn't respond” –as occurs in about half of all patients who are treated –“those patients who already have cirrhosis are at a far greater risk for developing liver cancer or suffering liver failure," notes Afdhal. In fact, he says, hepatitis C is the leading cause of liver transplants in the U.S. Until now, no treatment has been available for these patients.

In his first presentation, Afdhal will describe results from the COPILOT [Colchicine versus PEG-INTRON Long-Term] study, which was designed by Afdhal and colleagues at BIDMC to test the long-term use of low-dose interferon among hepatitis C patients. Conducted at 40 sites nationwide, the findings are the first to demonstrate that the progression of hepatitis C can be prevented or delayed through long-term maintenance therapy with peginterferon alfa-2b.

According to Afdhal, researchers found that peginterferon alfa-2B reduced by 50 percent the risk of patients reaching a clinical endpoint (variceal bleeding, liver failure, liver transplantation, hepatocellular carcinoma or death) and reported the results as part of a planned two-year interim analysis of the data.

"This is a new treatment paradigm, showing for the first time that we can prevent the serious complications of liver disease," he explains. "The results found that when used in this way, the therapy reduced by half the risk of the virus advancing to cause liver damage."

The COPILOT study tested weight-based low-dose peginterferon alfa-2b (0.5 mcg/kg/wk, injected subcutaneously) against colchicine (0.6 mg orally, twice daily), an anti-inflammatory and antifibrotic medication, in 550 chronic hepatitis C patients with advanced fibrosis who had previously failed interferon-based therapies. A total of 59 patients reached a clinical verified endpoint: 39 in the colchicine group versus 20 in the peginterferon alfa-2b group (p=0.003). The annual clinical event rate was approximately five percent (7.0 percent vs. 3.5 percent for colchicine and peginterferon alfa-2b, respectively), underscoring the need for better treatments to prevent disease progression.

Afdhal noted that the low 0.5 mcg/kg weekly dose of peginterferon alfa-2b used in the study â€“ one-third the dose used in standard combination therapy â€“ was well tolerated by patients and spared them the side effect of developing hemolytic anemia, which is often associated with ribavirin use.

"Patient adherence to their prescribed regimen is critical to success in hepatitis treatment and is an important consideration for long-term maintenance therapy," he said.

The COPILOT study was supported by Schering-Plough Corporation, manufacturer of peginterferon alfa-2b.

Afdhal's second presentation will describe results from a Phase II clinical trial of a new antiviral agent, NM283, being tested in humans for the first time.

The new drug shows activity against hepatitis C genotype 1 (HCV). One of six genotypes in existence, genotype 1 is the most predominant strain in the U.S., Japan and Western Europe, and is particularly difficult to treat.

Unlike existing therapies, which are administered by injection, NM283 is taken orally, says Afdhal, adding that it also has fewer side effects than existing agents. NM283 is the first in a new class of designer drugs, a polymerase inhibitor, specifically designed to block a step in HCV viral replication.

"This drug is a new class of treatment for HCV and represents significant hope for future therapies," he noted. "Data from these clinical trials are encouraging and suggest that NM283 may prove to be another treatment option [for hepatitis C patients]." NM283 was shown to have direct and significant antiviral activity against HCV as a single agent in both Phase I and Phase II clinical trials. Combining NM283 with interferon also showed promising activity, according to Afdhal.

NM283 was developed by Idenix Pharmaceuticals, Inc., which sponsored the Phase II clinical trial.

Beth Israel Deaconess Medical Center is a major patient care, teaching and research affiliate of Harvard Medical School, and ranks third in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a research partner of Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information visit www.bidmc.harvard.edu.

Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center

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November 2nd, 2004

Human Genome Sciences Reports Positive Results of Phase 1/2 Clinical Trial of Albuferon(TM) in Chronic Hepatitis C
SourceURL: http://biz.yahoo.com

- Data Demonstrate Safety, Prolonged Half-Life, and Dose-Dependent Antiviral Activity - - Presented at the 55th Annual Meeting of the American Association for the Study of Liver Diseases -

ROCKVILLE, Md., Nov. 2 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. (Nasdaq: HGSI - News) announced today that results from a Phase 1/2 clinical trial of Albuferon(TM) in treatment-experienced adults with chronic hepatitis C demonstrate that Albuferon is well tolerated, has a prolonged half-life, is biologically active and able to reduce viral load with dose-dependent magnitude and durability. The results were presented at the 55th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), which concludes today in Boston, MA. Albuferon is Human Genome Sciences' long-acting form of recombinant interferon alpha.

In an oral presentation, entitled "Albuferon -- A Novel Therapeutic Agent for Hepatitis C: Results of a Phase 1/2 Study in Treatment-Experienced Subjects with Chronic Hepatitis C" (Abstract #265), data were presented on 119 patients treated in a multi-center, open-label, dose-escalation study.(1) The Phase 1/2 clinical trial was designed to evaluate the safety, tolerability, immunogenicity, and pharmacokinetics of Albuferon in adults with chronic hepatitis C who have failed previous interferon alpha treatments. Antiviral activity also was evaluated. One hundred and nineteen subjects were enrolled into twenty-two treatment cohorts. Ninety-two percent of the patients (110 of 119) were infected with hepatitis C virus (HCV) genotype 1, which accounts for nearly seventy percent of all HCV infections in the United States and is generally regarded as the most difficult HCV genotype to treat. Patients participating in the study had been treated for an average of 63 weeks with interferon alpha or pegylated interferon alpha, either alone or in combination with ribavirin, prior to entering the Albuferon study. Patients in the Phase 1/2 clinical trial received one or two doses of Albuferon administered subcutaneously fourteen days apart. Doses administered ranged from 7-900 mcg.

The Phase 1/2 clinical trial results show that Albuferon is well tolerated, with adverse events that were mostly transient and mild to moderate in severity, and with no discontinuations due to adverse events or reductions in hematologic cell counts. A newly developed, highly sensitive assay, meeting current requirements for detecting the presence of antibodies to interferon alpha, was used to evaluate immunogenicity. Preliminary immunogenicity data presented at the AASLD meeting show that the vast majority of Albuferon antibody titers were low (<100 ng/mL) and that there is no apparent correlation between the emergence of antibodies and adverse events, antiviral response or pharmacokinetics. It was determined that 11.8 percent of the patients participating in the Phase 1/2 study had pre-existing antibodies to interferon. The observed rate of emerging Albuferon antibody- positive subjects was 10.9 percent. The immunogenicity rates reported for pegylated interferons in treatment-naove subjects range from 6.0-15.0 percent. The observed rate of neutralizing antibodies was 1.7 percent. The reported rates for neutralizing antibodies for pegylated interferons range from 1.0-5.0 percent in treatment-naove subjects. It was observed that 3.4 percent of those participating in the trial had pre-existing antibodies to albumin, while the observed rate of emerging albumin antibody-positive subjects was 1.7 percent.

The data presented show that Albuferon remains in the blood substantially longer than is reported for recombinant interferon alpha and pegylated interferon alpha. Albuferon is detectable for up to four weeks following a single subcutaneous injection. The Cmax (peak drug level) increases in a linear manner over the dose range evaluated. Albuferon exhibits a median half-life of 140 hours, supporting dosing at intervals of 2-4 weeks. This compares to a reported mean elimination half-life of 80 hours (50-140 hours) for Pegasys and 40 hours (22-60 hours) for PEG-Intron.(2, 3)

Viral load levels represent the quantity of hepatitis C virus in the blood and are a marker for drug activity. Forty-seven percent (37/78) of Albuferon- treated patients in the combined single-dose and two-dose cohorts at doses of 120-900 mcg experienced an antiviral response, as demonstrated by reductions in viral load of 1.0 log or greater. Mathematical modeling of viral dynamics and kinetic analysis of the viral decline in the single-dose cohorts demonstrate that the antiviral response was biphasic, with a dose-dependent first phase decline in viral load during the first one-two days, followed by a slower second phase decline until day 14. The data presented show that both magnitude and duration of early anti-viral response were dose-dependent.

Vijayan Balan, M.D., a lead investigator and Director, Hepatobiliary Clinic, Division of Transplant Medicine and Division of Gastroenterology and Hepatology, Mayo Clinic Hospital, Phoenix, AZ, said, "Currently, most patients with chronic hepatitis C are treated with pegylated interferon once weekly, along with daily doses of ribavirin. The available therapies frequently are associated with side effects that often require dose adjustments and can require discontinuation of treatment. There is a significant need to provide these patients with treatment options that are more convenient and hopefully have fewer side effects. The clinical results presented today demonstrate that Albuferon has a favorable safety and tolerability profile, is biologically active and able to reduce viral load with dose-dependent magnitude and durability. The pharmacokinetic behavior of Albuferon supports dosing at intervals of two to four weeks. Further evaluation of Albuferon as a potential treatment for chronic hepatitis C is warranted in Phase 2 clinical trials."

David C. Stump, M.D., Executive Vice President, Drug Development, said, "We are encouraged by the results presented today from our Phase 1/2 study of Albuferon in patients with chronic hepatitis C, particularly considering that the study was conducted in a heavily pretreated population. The data show that Albuferon is well tolerated, with mostly transient adverse events that were mild to moderate in severity, and with no discontinuations due to adverse events. We used a new, more sensitive assay to evaluate immunogenicity, which meets the current requirements for detecting the presence of antibodies to interferon. The preliminary immunogenicity data presented today show rates consistent with those reported for other interferon alpha-based therapies, with no apparent correlation between the emergence of these antibodies and adverse events, antiviral response or pharmacokinetics. Importantly, significant evidence of antiviral activity was observed. Nearly half of the patients treated with Albuferon at doses greater than 120 mcg experienced reductions in their viral load of 1.0 log or greater. Both magnitude and duration of viral response were dose-dependent. Based on the clinical and preclinical results to date, we are continuing to evaluate Albuferon in Phase 2 studies."

Craig A. Rosen, Ph.D., President and Chief Operating Officer, said, "The results reported today reinforce our belief that Albuferon has the potential to provide these patients with a new long-acting treatment option, with a considerably more convenient treatment schedule, and perhaps with improved efficacy or safety."

Albuferon is a novel, long-acting form of interferon alpha. Recombinant interferon alpha is approved for the treatment of hepatitis C, hepatitis B, and a broad range of cancers. Human Genome Sciences modified interferon alpha to improve its pharmacological properties by using the company's proprietary albumin fusion technology. Albumin fusion technology allows scientists to create novel, next-generation protein drugs by fusing the gene that expresses human albumin to the gene that expresses a therapeutically active protein. Albuferon results from the genetic fusion of human albumin and interferon alpha. Human Genome Sciences is developing Albuferon for use in the treatment of chronic hepatitis C.

Hepatitis C infection is an inflammation of the liver caused by the hepatitis C virus. Hepatitis C infection is currently the most common chronic blood-borne infection in the United States, afflicting four times as many people as are infected with HIV, the virus that causes AIDS. The hepatitis C virus is transmitted primarily through significant or repeated exposures to infected blood. In the United States, intravenous drug use and sexual contact with infected persons account for the majority of new hepatitis C infections. When detectable levels of the hepatitis C virus in the blood persist for at least six months, a person is diagnosed as having chronic hepatitis C. Approximately four million people in the United States are infected with the hepatitis C virus, and between sixty and eighty-five percent of hepatitis C- infected people develop chronic hepatitis C. A four-fold increase in the number of adults diagnosed with chronic hepatitis C is projected from 1990 to 2015.(4)

For additional information on Human Genome Sciences, please visit our web site at http://www.hgsi.com. For more information on Albuferon, see http://www.hgsi.com/products/
albuferon.html.

Health professionals interested in the Albuferon trial or any other study involving HGSI products are encouraged to inquire via the Contact Us section of the Human Genome Sciences web site, http://www.hgsi.com/products
/request.html, or by calling us at (301) 610-5790, extension 3550.

Human Genome Sciences is a company with the mission to treat and cure disease by bringing new gene-based drugs to patients.

HGS, Human Genome Sciences, and Albuferon are trademarks of Human Genome Sciences, Inc.

This announcement contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The forward-looking statements are based on Human Genome Sciences' current intent, belief and expectations. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Actual results may differ materially from these forward-looking statements because of the Company's unproven business model, its dependence on new technologies, the uncertainty and timing of clinical trials, the Company's ability to develop and commercialize products, its dependence on collaborators for services and revenue, its substantial indebtedness and lease obligations, its changing requirements and costs associated with planned facilities, intense competition, the uncertainty of patent and intellectual property protection, the Company's dependence on key management and key suppliers, the uncertainty of regulation of products, the impact of future alliances or transactions and other risks described in the Company's filings with the Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today's date. Human Genome Sciences undertakes no obligation to update or revise the information contained in this announcement whether as a result of new information, future events or circumstances or otherwise.

Footnotes:

1. Balan V, et al. Albuferon(TM) -- A Novel Therapeutic Agent for Hepatitis C: Results of a Phase 1/2 Study in Treatment Experienced Subjects with Chronic Hepatitis C. 55th Annual Meeting of the American Association for the Study of Liver Diseases, Boston. November 2, 2004. Oral presentation (Abstract #265).

2. PEGASYS(R) Physicians Desk Reference. (Last updated December 2002).

3. PEG-INTRON(R) Physicians Desk Reference. (Last updated August 2002).

4. Management of Hepatitis C: 2002. National Institutes of Health

Consensus Development Conference.

Source: Human Genome Sciences, Inc.

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Anadys Pharmaceuticals Reports Hepatitis C Viral Load Reduction in Completed Phase Ib Clinical Trial of Isatoribine

New Data Presented at AASLD Annual Meeting in Boston Demonstrate Biological Activity in HCV Patients through Activation of Toll-Like Receptor 7

San Diego, Nov. 3, 2004 -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS), a biopharmaceutical company committed to the discovery, development and commercialization of novel medicines to treat chronic viral hepatitis and bacterial infections, reported new data from a recently completed multi-component Phase IB clinical trial of isatoribine (ANA245) at the American Association for the Study of Liver Diseases (AASLD) Annual Meeting yesterday in Boston. The isatoribine family of compounds, which includes ANA975, Anadys' development candidate for frontline treatment of chronic hepatitis C virus (HCV) infection, is a new class of drugs being developed by Anadys to regulate innate immunity by interacting with Toll-Like Receptor 7.

In a presentation entitled "Isatoribine, a Toll-Like Receptor 7 Agonist, Significantly Reduced Plasma Viral Load in a Clinical Proof-of-Concept Study in Patients with Chronic Hepatitis C Virus (HCV) Infection," Yves Horsmans, M.D., Professor at Cliniques Universitaires St. Luc in Brussels and Principal Investigator of the study, reported that isatoribine was safe, well tolerated and biologically active in the study. Although long-term therapeutic utility was not a stated objective of the Phase IB clinical trial and the number of patients was relatively small, results demonstrated a statistically significant viral load reduction in the plasma of patients chronically infected with HCV.

"The data from this trial provide the first evidence that a selective agonist of Toll-Like Receptor 7 can reduce circulating levels of HCV by activating innate immunity while avoiding the intense adverse effects often observed with current standard-of-care therapies," said Prof. Horsmans.

The Phase IB clinical trial was designed to test the safety and tolerability of isatoribine in patients chronically infected with HCV. The study was a dose-escalating, open-label evaluation of isatoribine administered intravenously over a period of seven days to 32 adult patients at 200 mg, 400 mg, 600 mg and 800 mg daily doses. The trial was conducted at two clinical centers in Western Europe. Patients participating in the study were either HCV-treatment naïve or relapsed from interferon-alpha, a component of the current standard of treatment. Of the 32 patients in the study, 23 were infected with HCV genotype 1, which accounts for more than two-thirds of the infections in the United States yet is the most difficult to treat with current therapies.

Study results showed that isatoribine was biologically active, as evidenced by statistically significant changes in 2'-, 5'-oligoadenylate synthetase (OAS), a biological marker for the activity of interferon-alpha that is believed to mediate antiviral effects, in patients who received either 600 mg or 800 mg daily for seven days. The amount of HCV in the bloodstream, or plasma viral load, was most significantly reduced in patients receiving 800 mg daily doses. After seven days, the average decrease in plasma viral load was 0.76 log10 units, or 82 percent, in these patients. Of the 12 patients in this 800 mg dose group, 10 were infected with HCV genotype 1. After completing the dosing phase, OAS expression and plasma viral load returned to pre-treatment levels in all patients within seven days.

Isatoribine treatment was safe and well tolerated in the study, with no serious adverse events and a low frequency of mild to moderate side effects, although definitive conclusions regarding product safety cannot be made until the results of future clinical trials of longer duration in more patients are known. No patient altered treatment or withdrew from the study due to adverse events or clinical laboratory abnormalities. The results from this completed clinical trial corroborate and extend previously disclosed safety, tolerability, and pharmacokinetic data derived from single doses of isatoribine in healthy volunteers and from other components of the Phase IB clinical trial.

"We are very encouraged by the results of this study, which provide the foundation for an upcoming clinical trial of our oral prodrug ANA975 for potential frontline treatment of chronic HCV," said Steve Worland, Ph.D., Anadys' Executive Vice President, Research and Development.

About Hepatitis C

Hepatitis C virus, the most common chronic blood-borne infection in the United States, causes inflammation of the liver and may progress to more serious complications such as cirrhosis of the liver, liver cancer and death. Approximately 2.7 million people in the United States are chronically infected with HCV, and the Centers for Disease Control (CDC) estimates that by the year 2010, the number of deaths attributed annually to HCV could surpass that due to HIV/AIDS. Worldwide sales for HCV products were an estimated $2.7 billion in 2003, yet current treatments for HCV may be ineffective in up to 50 percent of patients due to the development of drug-resistant viral strains, and many treatments are associated with serious side effects.

About Anadys

Anadys Pharmaceuticals, Inc. (www.anadyspharma.com) is a biopharmaceutical company committed to advancing patient care by discovering, developing and commercializing novel small molecule, anti-infective medicines for the treatment of hepatitis C virus (HCV), hepatitis B virus (HBV) and bacterial infections. Anadys is advancing its anti-infective portfolio through the development of its two clinical programs, the isatoribine family of compounds including the oral prodrug ANA975 for the treatment of HCV, and ANA380 for the treatment of HBV. In addition, Anadys' anti-infective therapeutic platform is designed to advance a strong and continual pipeline of drug candidates into the clinic.

Statements in this press release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, references to the biological activity of isatoribine in HCV infected patients, viral load reduction resulting from administration of isatoribine to HCV infected patients, the effect on a patient's immune system and the potential for ANA975 to become an orally administered front-line treatment for chronic HCV. Such forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause the actual results of Anadys Pharmaceuticals to be materially different from historical results or from any results expressed or implied by such forward-looking statements. In particular, the results of initial clinical trials are not necessarily predictive of future results, and Anadys can provide no assurances that isatoribine or ANA975 will have favorable safety, tolerability or efficacy results in later clinical trials, or receive regulatory approval. Such forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause Anadys' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. In particular, the results of initial clinical trials may not be predictive of future results, and Anadys cannot provide any assurances that any of its product candidates will have favorable results in later clinical trials or receive regulatory approval. In addition, Anadys' results may be affected by competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to successfully develop and market products, difficulties or delays in its clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its products, regulatory developments involving future products and its ability to obtain additional funding to support its operations. These and other factors that may cause actual results to differ are more fully discussed in the "Risk Factors" section of Anadys' Form 10-Q for the quarter ended June 30, 2004.

All forward-looking statements are qualified in their entirety by this cautionary statement. Anadys is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

Michael Kamdar
Sr. Vice President, Corporate Development & Finance
Anadys Pharmaceuticals, Inc.
(858) 530-3667
cc@anadyspharma.com

Pete De Spain
Manager, Corporate Communications
Anadys Pharmaceuticals, Inc.
(858) 530-3653
pdespain@anadyspharma.com

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ICAAC: Response to Pegylated Interferon A-2b Predicts Clearance of Hepatitis C Virus in Patients Co-Infected With HIV
SourceURL:http://www.docguide.com/
Ed Susman

WASHINGTON, DC -- November 2, 2004 -- An early decrease in hepatitis C viral load in a patient who is co-infected with HIV is highly predictive of whether that patients can clear the hepatitis C infection after 1 year. "If the patients respond and reduce viral load by 4 weeks," said Christopher Payan, MD, staff physician at Angers Hospital, Angers, France, "they have a 97% chance of a cure for hepatitis C virus." In an oral presentation here on October 31[st at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Dr. Payan said that the study indicates that evaluation of track-C, the core antigen of hepatitis C virus, is correlated with treatment outcome, and the development of an assay for the core antigen may become a valuable monitoring tool.

Dr. Payan said that patients who do not have a major response against hepatitis C virus after 4 weeks have almost no chance of treatment success.

"If we see that the patient is not responding after 4 weeks [of treatment], it may be that we have the opportunity to switch that patients to other treatments," said Bassel Amer, MD, chief of product development, Schering-Plough, Levallois-Perret, France, which sponsored the study.

Dr. Payan and colleagues conducted the RIBAVIC study, a randomized, controlled trial of pegylated interferon a-2b plus ribavirin versus standard interferon alfa-2b plus ribavirin in 400 patients co-infected with HIV and HCV. He presented the results of a substudy, which reviewed the charts of 304 of these patients.

In his presentation, Dr. Payan explored the positive and negative predictive values of intermediate evaluation of viral loads of hepatitis C virus. He noted that the RIBAVIC trial was a real-life clinical investigation with a cohort that was representative of patients seen in a clinical practice.

"These patients had high percentages of cirrhosis; they were drug addicts, they were not the very well-defined subjects often recruited for clinical trials," Dr. Amer said.

Dr. Payan noted that in addition to the ability of the viral load to predict outcome, "total hepatitis C viral core antigen appears to be an early predictor of response to the treatment."

[Presentation title: Comparison of HCV RNA and HCV Core Antigen Kinetics in the Follow-Up of a Therapeutic Protocol in HCV-HIV Co-Infected Patients (RIBAVIC). Abstract V-1149]

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November 3rd, 2004

Drug Combination May Become New Treatment Paradigm for Hepatitis C Virus SourceURL:http://www.docguide.com
Mark L. Fuerst

BOSTON, MA -- November 3, 2004 -- The combination of a novel, oral polymerase inhibitor and pegylated interferon, may become the new treatment paradigm for hepatitis C virus (HCV) infections, according to results of an interim analysis presented here on November 1st at the 55th Annual Meeting of the American Association for the Study of Liver Diseases.

This new combination "may offer improved efficacy outcomes, especially for HCV patients who are nonresponders or have failed to clear the virus with standard therapy," said Nezam Afdhal, associate professor of medicine at Harvard University.

During his presentation, Dr. Afdhal said that the polymerase inhibitor, NM 283, is the first in a new class of designer drugs that specifically block a step in HCV viral replication. Unlike existing therapies, which are administered by injection, NM 283 is taken orally and appears to have fewer adverse effects than existing agents, Dr. Afdhal said.

He presented data from an ongoing, phase 2, clinical study that evaluated the combination of NM 283 and pegylated interferon. The trial includes 30 treatment-naÃ¯ve patients with compensated chronic HCV infections. They received NM 283 in escalating daily doses of 400-, 600-, and 800-mg, alone or in combination with pegylated interferon 1.0 mcg/kg subcutaneously on days 8, 15, and 22. At day 8 they reached the 800-mg dose of NM 283.

Dr. Afdhal presented results from an interim analysis of 19 patients, 12 in the combination arm and 7 in the NM283 alone arm. He said that 75% of patients treated with the combination experienced early virologic response. An early virologic response was correlated with an improved chance of sustained viral clearance, he said.

Patients receiving the combination therapy achieved a mean 2.7 log viral load reduction through week 4, representing a 99.8% reduction in HCV RNA. Dr. Afdhal said that this result is consistent with preclinical data that suggested a synergistic antiviral effect for the combination of NM 283 plus interferon-alfa.

Dr. Afdhal said the safety of the combination therapy was "satisfactory, with typical side effects expected with interferon, and a high compliance rate [more than 90%]."

"This is the first agent in the class to be effective, it has a good safety profile, and is additive with interferon. It's the start of a new paradigm for treating HCV infection," Dr. Afdhal said.

[Presentation title: "Final Phase I/II Trial Results for NM283, a New Polymerase Inhibitor for Hepatitis C: Antiviral Efficacy and Tolerance in Patients with HCV-1 Infection, Including Previous Interferon Failures." Abstract LB03]

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Attention, Treatment for Mental and Physical Fatigue in Hepatitis C Patients
SourceURL:http://www.docguide.com
Maria Bishop

BOSTON, MA -- November 3, 2004 -- Patients with hepatitis C virus (HCV) rank both mental and physical fatigue as their primary complaint, according to research reported here on November 1[st at the 55th Annual Meeting of the American Society for Liver Diseases.

In addition, a second study presented here on October 30th showed that there is a possibility that ondansetron might be an effective treatment for that complaint.

Ondansetron has been shown to be effective in patients with chronic fatigue syndrome and in chronic liver disease, prompting researchers to investigate its uses in patients with chronic HCV, noted Albert Tran, MD, professor of hepatogastroenterology, Archet Hospital 2, Nice, France.

In a randomized, placebo-controlled, double blind trial, the Dr. Tran's team enrolled 36 patients with for whom fatigue was the predominant symptom, scoring more than 4 out of 0-10 on a visual analog scale (VAS).

Patients were treated with oral ondansetron 4 mg twice daily or placebo for 1 month, followed by 4 weeks of observation. Fatigue and depression were measured on day 0, 15, 30 and 60 using the Fatigue Impact Scale and Beck Depression Inventory, a validated self-report questionnaire.

Compared to placebo, ondansetron was shown to significantly reduce fatigue, with 30% improvement at day 15 (P <.01), day 30 (P <.01) and day 60 (P <.01). Ondansetron also significantly reduced fatigue at day 15 (P =.03) and day 60 (P =.04) compared to placebo; the difference reached statistical significance at day 30 (P =.1).

These observations support the concept that fatigue involves serotoninergic pathways, and even though Dr. Tran noted that ondansetron is too expensive yet to be indicated for purpose, such data may encourage further evaluation of the alteration of central serotoninergic neurotransmission to combat fatigue in chronic liver disease.

In a second poster presentation to involve the topic of HCV symptoms, Australian researchers evaluated the efficacy of the Short Form-36 (SF-36) questionnaire as a tool for measuring health-related quality of life (QoL) in HCV, and developed an instrument that they say is more closely correlated to measuring the impairments of QoL seen in patients with chronic liver disease.

Lead investigator Carolyn Lang, MS, postgraduate candidate in the research department, Centre for Diabetes and Endocrine, The University of Queensland, Brisbane, Australia, noted that a cross-sectional interview-based study of 160 HCV patients led to a roster of 21 major QoL symptoms ranked by prevalence and severity. The top-ranked symptom was physical tiredness, with nearly 86% of subjects citing fatigue as their primary QoL obstacle. Physical tiredness was given a severity rank of 7 on a VAS.

A principal components analysis with varimax rotation was undertaken on the 21 symptoms, extracting 4 clusters of symptoms affecting QoL -- neuropsychiatric, gastrointestinal, algesic and dysesthetic.

In an assessment of the relationship between symptom clusters and SF-36 scores, the researchers first compared the SF-36 scores with Australian normative data. Their results showed that people living with HCV had significantly lower SF-36 scores than a healthy Australian population (P <.001). Although widely used, the SF-36, however, did not correlate well with the symptoms present in the gastrointestinal and dysesthetic clusters of this cohort, and did not accurately identify these impairments to QoL in people living with HCV.

Ms. Lang noted that her team is in the process of developing a symptom profile for HCV patients that could be used by governments or managed-care organizations to help prioritize treatment, provide assistance and aid in disability-related issues.

"For [HCV] patients who are on government assistance, for example," Ms. Lang noted, "it is imperative to have a way of measuring fatigue. How can they apply for 4 or 5 jobs a week to keep their unemployment benefits when their illness is such that they cannot get out of their beds some days?"

All patients interviewed for this study were from Queensland, Australia, with 61% from metropolitan Brisbane.

[Presentation title: "Effect of Ondansetron, a 5-HT3 Receptor Antagonist, on Fatigue in Chronic Hepatitis C: a Randomized Double Blind Placebo Controlled Study." Abstract 354.

"Impairments in Quality of Life Due to Symptom Clusters in People Living With Chronic Hepatitis C Infection Are Poorly Identified By the Short Form 36 (SF-36)." Abstract 803]

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Successful Phase I Clinical Trial of spi-VECTM Oral Hepatitis B Vaccine Paves the Way for Phase II Efficacy Trial
SourceURL:http://biz.yahoo.com/prnews

WOKINGHAM, England, November 3 /PRNewswire/ -- Microscience is today announcing further significant results from a Phase I clinical study of its spi-VECTM oral immunotherapeutic vaccine designed for the treatment of subjects chronically infected with the hepatitis B virus ("HBV"). The trial met its primary objectives and successfully demonstrated safety and immunogenicity, supporting the vaccine's continued development as a therapeutic for chronic HBV carriers.

A Phase I, open-label, dose-escalating study was performed in 30 healthy adult volunteers to evaluate the safety and immunogenicity of a candidate oral immunotherapy given on two occasions, 56 days apart.

The primary aim of the study was to assess safety and to determine the cellular immune responses against hepatitis B core antigen ("HBcAg") raised by two dose levels of this novel vaccine. It is known that a cellular immune response is critical for an immunotherapy to be effective against this life-threatening infection.

The vaccine was shown to be safe and well tolerated. The immunological data have demonstrated that all subjects mounted a T-cell proliferative response to both the HBcAg and to groups of peptides representing the whole sequence of HBcAg, indicating that the antigen had been successfully delivered to the immune system in all subjects. In addition, 95% of responders in the high dose group elicited a Th1-biased response characterised by the secretion of gamma interferon and the absence of IL-5 secretion by stimulated T-cells. Th1 responses are known to play an important role in the promotion of viral clearance in chronic hepatitis B. The excellent safety profile and the powerful immunological data generated in this Phase I study support the further development of this important immunotherapeutic vaccine.

Rod Richards, Chief Executive Officer, commented: "There are some 350 million carriers of chronic hepatitis B carriers worldwide, accounting for one million deaths per year and current treatments offer only limited efficacy. These results are very exciting as they demonstrate that the spi-VECTM-based vaccine stimulates the appropriate type of immune response required to promote clearance of the hepatitis B virus in chronic carriers. Having successfully demonstrated in this study both the immunogenicity of this oral hepatitis B vaccine and a favourable safety profile, we are now planning a Phase II programme in subjects chronically infected with the virus. The vaccine could also pave the way for the development of a new generation of immunotherapeutic vaccines, using spi-VECTM technology, targeting a range of chronic viral diseases."

These results, together with those recently announced using Microscience's spi-VECTM ETEC travellers' diarrhoea vaccine, exemplify the potential of the platform and demonstrate its utility in two key disease indications. Microscience is also harnessing the spi-VECTM platform technology to develop other new oral vaccines to protect against typhoid and anthrax. The Company is currently seeking development partners for its spi-VECTM vaccine programmes.

Notes to Editors:

About Hepatitis B
Most people who become infected with hepatitis B will clear the infection, however, in 2 to10 percent of infected adults the immune system fails to clear the virus and these subjects consequently become carriers of the virus. In children, the number that become carriers after infection is much higher. The consequences of carrying the virus can be devastating; these patients are at high risk of developing chronic liver disease such as cirrhosis and primary liver cancer.

The group of chronically infected patients most at risk of developing liver disease are those in which viral replication can be detected. Currently available therapies for this patient population consist mainly of alpha-Interferon and antiviral drugs. Their efficacy is limited and long-term use is problematic due to either safety concerns or the development of resistant forms of the virus. Microscience believes there is a clear need for a new treatment for chronically infected patients with active viral replication to prevent development of liver disease and reduce transmission of the virus.

About spi-VECTM
The spi-VECTM vaccine consists of a harmless Salmonella bacterium that has been modified to carry the hepatitis B core antigen. The Salmonella bacterium then acts as a vehicle to deliver the antigen directly to cells of the immune system resulting in effective antigen presentation with resultant strong immune responses.

Immunotherapy against HBV that is able to induce interferon gamma production from CD4+ Th1 cells and intra-hepatic CD8+ T cells in chronic carriers may promote clearance of the virus. Therefore administration of HBcAg using a vector system such as spi-VEC that expresses the antigen intracellularly, followed by processing and correct display of peptides to the immune system, may be effective in generating a sustained Th1 response, strong enough to promote clearance of virus-infected cells.

Rationale for use of Hepatitis B core antigen

The nucleocapsid (core) of HBV is a particle made up of multiple copies of a single 21 kDa polypeptide subunit encoded by the hepatitis B core gene. In chronic carriers HBcAg is not found circulating in the blood, and hence, the virus minimises the exposure of this antigen to the patient's immune system. The intact hepatitis B core structures are highly immunogenic, eliciting much stronger humoral and cellular responses than vaccines containing hepatitis B surface antigens. The immunogenicity of HBcAg is well reported in the literature from various animal models and is expected to translate to an advantage over surface antigen preparations in terms of the magnitude of the immune response elicited in chronic carriers.

There are several lines of evidence to suggest that the HBcAg is more likely than surface antigen preparations to induce the type of immune response that may result in viral clearance in chronic carriers, or reduce viral load to prevent the sequelae of chronic infection. In acute hepatitis a strong Th1 response against HBcAg appears mandatory to prevent chronicity of infection and initiate the process of clearance.

Patients that clear the virus during the acute phase of infection mount a potent CD4+ Th1 and CD8+ T-cell response against a range of epitopes from all structural and non-structural hepatitis B viral proteins. However, the HBcAg appears to be the most important immune target to prevent chronic infection and initiate the process of viral clearance. In individuals who become chronic carriers, the CD4+ Th1 and CD8+ responses are weaker, recognise a narrower repertoire of epitopes and a Th2 response predominates. There is evidence to suggest that a CD4+ Th1 response and/or CD8+ T cell response against HBcAg are important to initiate and maintain viral clearance in chronic carriers. Moreover, in chronically infected patients who have episodes of acute exacerbation of the disease, a strong Th1 response to HBcAg is observed, that on occasions can lead to seroconversion or that is associated with a favourable outcome in patients administered exogenously produced interferon. Several studies have also been performed in animal models demonstrating the potential of HBcAg as an immunotherapy for clearance of chronic hepatitis B infection.

Another line of evidence comes from a study looking at bone marrow transplantation from hepatitis B virus immune subjects to chronic carrier recipients. Bone marrow from donors with antibodies to HBsAg and HBeAg or HBsAg antigen alone were transferred to chronic carrier recipients. Clearance of S antigen in the recipients was seen with bone marrow from donors with antibodies to S and HBeAg but not with donors who had antibody to S antigen alone. The donors who cleared the S antigen showed a specific Th1 response to hepatitis B cores.

Source: Microscience Ltd

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Health Professionals Fall Short for Hepatitis C Patients
SourceURL:http://www.scoop.co.nz

People living with Hepatitis C are highly critical of the treatment they have received from health professionals, particularly doctors, according to a new study by a University of Auckland sociology researcher.

The study, carried out by Magdalena Harris of the University’s Department of Sociology, involved interviews with 20 individuals living with Hepatitis C in the Auckland region. The results were presented for the first time last month to the Australasian Hepatitis C Conference in Canberra.

Almost all the people interviewed in the study reported at least one, and often multiple, negative encounters with doctors, nurses and dentists, according to Ms Harris. “Common were experiences of discrimination, ignorance and manipulation in their interactions,” she says.

“Many felt that the medical profession has a one-dimensional treatment based approach, whereas what is also needed is information about methods for managing the illness such as changes to diet.”

“Most research participants had consequently conducted their own research, looking to books and the Internet for methods to cope with the illness.”

The research also found that people living with Hepatitis C feel isolated and lack social support. Furthermore, public ignorance of the illness in New Zealand exacerbated the difficulties for people living with the disease.

“Participants said they felt there was a distinct stigma and silence about Hepatitis C in our society,” Ms Harris says. “This, together with a perceived social pressure to cope with the illness, resulted in people feeling uneasy about seeking support from others and ultimately choosing to hide the disease.”

“Over 60 percent of people interviewed also said they had suffered significant bouts of depression.”

Hepatitis C is a virus which affects the liver and is transmitted by blood to blood contact. It primarily affects intravenous drug users or people who have had blood transfusions prior to July 1992.

Ms Harris says there are an estimated 30,000- 40,000 people living with Hepatitis C in this country. “Symptoms are varied, but many sufferers experience fatigue, nausea, depression, irritability and sensitivity to light, noise and certain foods. Serious cases of Hepatitis C can result in cirrhosis or liver cancer.”

Ms Harris says her study found that participants who were actively involved in support networks exhibited lower levels of distress and isolation. “An increase in peer support networks is desirable as this is an important factor in maintaining the physical and mental well-being of people with hepatitis C.”

“I also believe that drug use needs to move from being seen as a criminal activity to a health issue. In my view this would lessen the stigma associated with Hepatitis C and encourage help-seeking behaviour.”

The participants in the study were randomly selected from Narcotics Anonymous and the HCV Resource Centre, a Ministry of Health funded resource centre for information about Hepatitis C.

Ms Harris acknowledges that a larger representative study is needed in New Zealand.

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Hepatitis a Hidden Mystery
AMY PATTERSON
http://www.stuff.co.nz/

Discrimination against people with hepatitis C is similar to that against HIV sufferers in the epidemic's early days.

An Auckland University sociology department study of 20 people with hepatitis C found many are afraid to disclose their illness.

Magdalena Harris completed the research for her masters degree and says the isolation among hepatitis C sufferers is "staggering".

"It's been described as being treated like HIV was in the 1980s. HIV now seems to be more of a mainstream disease," she says.

She says sufferers feel branded with what's seen as a junkie's disease. Some of the people broke down in tears and told her she was the first person they'd had to talk to about their isolation.

Hepatitis C is not a notifiable disease in New Zealand. It is estimated about 30,000 suffer itbut Ms Harris believes it's more like 40,000.

It is a virus that affects the liver and is transmitted by blood to blood contact. It primarily affects intravenous drug users or people who have had blood transfusions before July 1992.

AdvertisementAdvertisement"People don't want to tell their friends or family they've got hepatitis C because there's so much ignorance," she says.

"People think it's really easy to get."

New Zealand Aids Foundation spokesman Steve Attwood says people feared those with HIV in the 1980s because they didn't know how it was transmitted.

"It's fair to say there's still a lot of stigma around HIV," Mr Attwood says.

He says HIV is still perceived as a homosexual disease, even though it affects many heterosexual people.

Ms Harris' research found most discrimination was due to public ignorance of hepatitis C.

"That together with a perceived social pressure to cope with the illness, resulted in people feeling uneasy about seeking support from others and ultimately choosing to hide the disease," she says.

More than 60 per cent of people interviewed had also suffered significant bouts of depression.

Auckland Hepatitis C Resource Centre manager Robyn Brown gets many inquiries from families and friends wanting to know how the disease is transmitted.

"Until they find out they can be uncomfortable with hep C people being close to them," she says.

More young people are contracting the disease from using methamphetamine, or P, either intravenously or snorting.

Many do not give their name when inquiring about hepatitis C.

Ms Harris' study found infected people who were actively involved in support networks showed lower levels of distress and isolation.

People were randomly selected from Narcotics Anonymous and the Hepatitis C Resource Centre for the study.

Hepatitis C symptoms include fatigue, nausea, depression, irritability and sensitivity to light, noise and certain foods. Serious hepatitis C cases can cause cirrhosis or liver cancer.

Ms Harris will further the research during her doctoral studies next year.

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Canadian Hemophilia Society Responds to Health Minister's Commitment to Present Cabinet with a Compensation Proposal

OTTAWA, ONTARIO--(CCNMatthews - Nov. 3, 2004) - The Canadian Hemophilia Society (CHS) is cautiously optimistic that people infected with the Hepatitis C Virus (HCV) through tainted blood received before January 1, 1986 or after June 30, 1990 could receive financial compensation from the federal government within months. Responding to news that the Federal Health Minister Ujjal Dosanjh will present Cabinet with a compensation proposal as early as tomorrow, CHS Vice-President John Plater expressed hope that a new approach would receive immediate approval. "Minister Dosanjh has taken a fresh view of the circumstances and demonstrated a desire to be compassionate and reasonable to ensure that all people affected by this terrible tragedy are treated fairly and equally," said Plater. "We hope that his Cabinet colleagues take a similar position so that work on details for a comprehensive compensation plan can begin immediately."

Last night Plater watched from the gallery of the House of Commons as members of all opposition parties called on the government to reverse the position of the former Chretien government and extend compensation to all people infected with HCV though the blood supply. Member after member of the Liberal minority government expressed a desire to find a way to extend assistance to all people infected with HCV though the blood supply based on their current understanding of the file. In response, the opposition parties indicated their intention to bring the matter to a vote in the minority-lead house.

In 1997, the Commission of Inquiry into the State of the Canadian Blood Supply System, headed by Justice Horace Krever, recommended compensation for all people harmed by the blood system, regardless of when they were infected. In 1998, the Federal, Provincial, Territorial (F/P/T) Governments proposed and subsequently established a $1.2 billion legal settlement (the "86-90" Agreement") for people who became infected with HCV through the blood system between 1986 and 1990. People infected with HCV through the blood system prior to January 1, 1986 or after June 30, 1990 were not offered any direct assistance at the time. Original estimates that 22,000 people would be eligible under the 86-90 Agreement have proven incorrect as less than 5000 infected individuals have qualified as of November 2004. Based on the response to a small settlement negotiated with the Canadian Red Cross, the expected number of people excluded from the 86-90 Agreement is less than 5,500.

"It has taken government far too long to implement Justice Krever's recommendation to compensate everyone equally," said Plater. The CHS remains committed to ensuring that all people infected with HCV through the blood supply are treated fairly and equally. "We wish the Federal Liberal government of the day had treated everyone equally but we applaud the present Health Minister's desire to make equal treatment a reality as soon as possible," said Plater. In a minority government situation, given opposition support for the initiative, the outcome appears inevitable. "If Mr. Dosanjh has the government's support to see everyone treated fairly and equally, CHS is committed to supporting the process."

FOR FURTHER INFORMATION PLEASE CONTACT:

CHS
Chairperson, Hepatitis C/HCV Taskforce
John Plater, Vice-President
(519) 599-3093 (office)
(416) 525-4247 (cell)

CHS Hepatitis C Program
Jeff Rice
Coordinator
(514) 848-0503, #225

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November 5th, 2004

CDC: Hepatitis B Down among Children, Teens CNN.com

ATLANTA, Georgia (AP) -- Cases of hepatitis B among children and teenagers have dropped by almost 90 percent in the past decade, thanks to a vaccination program against the virus, the government said Thursday.

A total of 13,829 youngsters had hepatitis B in the United States between 1990 and 2002, the period of the study. The rate for that group dropped from 3.03 cases per 100,000 people in 1990 to 0.34 per 100,000 in 2002, the Centers for Disease Control and Prevention said.

A government recommendation that all infants get hepatitis B vaccinations was put in place in 1991. The program was expanded in 1995 to 11- and 12-year-olds and in 1999 to all children.

The hepatitis B attacks the liver. It can cause scarring of the liver, liver cancer, liver failure and death. The virus can be transmitted by casual contact with blood or other body fluids, as well as through sex or shared needles, or from mother to baby during birth.

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Britain Urged to Adopt Hepatitis Vaccine Programme
http://uk.news.yahoo.com

LONDON (Reuters) - Britain has been urged to follow the example of many other countries and adopt a universal vaccination programme against hepatitis B infection.

The illness, which is caused by the hepatitis B virus, is the most common liver infection. Each year it causes more than 500,000 deaths worldwide.

While other developed countries have hepatitis B vaccine programmes, Britain only immunises high risk groups such as health workers, drug addicts and homosexual men.

"Immunisation strategies targeting multiple risk groups have failed to provide adequate coverage in Britain and should be replaced by universal immunisation," Nicholas Beeching, of Liverpool University Hospital, said in an editorial in The British Medical Journal on Friday.

No one at the Department of Health was immediately available to comment.

Each year in Britain there are about 4,500 acute cases of hepatitis B infections and more than 7,500 new cases of chronic infections. The estimated cost to the state-funded National Health Service is between 26 million and 375 million pounds per year, he added.

"As the cost of vaccines has fallen, universal immunisation strategies have been adopted by over 150 countries, with evidence of effectiveness lasting more than 10 years."

In a clinical review of research into preventing and treating hepatitis B infection which was published in the journal, Rakesh Aggarwal, of the Institute of Medical Sciences in Lucknow, India said vaccination is the mainstay of prevention.

"Hepatitis B vaccines are highly effective, long-acting, and safe, making prevention and even eventual eradication possible," he said.

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Hepatitis C Linked to Half of U.S. Liver Cancer Cases
http://www.advocate.com

Researchers from the Liver Cancer Network report that the hepatitis C virus is involved in more than half of U.S. cases of liver cancer, Reuters Health reports. Liver cancer is increasing faster than any other type of cancer, according to a report presented by the researchers Monday in Boston at the annual meeting of the American Association for the Study of Liver Diseases. A study of 250 liver cancer patients showed that 52% were infected with HCV. Overall, 87% of liver cancer patients had some sort of underlying liver disease. St. Louis University researcher Alex S. Befeler, who presented the study data, said chemotherapy is typically ineffective for liver cancer, since liver damage makes drug metabolism poor. "Liver transplantation is the best approach," he said.

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The Glass Is Half Full in Process to Treat Hepatitis C Patients
Investors Business Daily
Amy Reeves

If you catch hepatitis C, the good news is there's a treatment for it. The bad news is it works only half the time.

According to the Centers for Disease Control, 3.9 million Americans harbor the hepatitis C virus (HCV). It leads to between 10,000 and 12,000 annual deaths from destruction of the liver.

The main treatment is pegylated interferon along with ribavirin, an anti-viral drug. The drug completely rids about half the patients of the virus.

So what to do with the other half?
That was the question preoccupying drug makers and researchers at the recent American Association for the Study of Liver Diseases conference. Though no one had a complete answer, the research pointed in a few different directions.

Battle Lines
The big guns in interferon are Roche and Schering-PloughSGP. They've been duking it out for market share.

Schering fired the latest salvo at the conference by presenting data that its drug, Peg-Intron, attacks HCV more quickly and destroys fewer white blood cells than Roche's drug.

Perhaps more significantly, Schering is taking a new tack toward patients who don't respond to Peg-Intron.

Another study showed promise for using very low doses of Peg-Intron as a "maintenance" therapy. It doesn't wipe out the virus, but it can stop or slow the spread.

Normally patients take interferon three times a day for 48 weeks. Doctors then monitor the patient for an additional 24 weeks.

If the virus makes no appearance in that time, the patient is cured. If it does, there isn't much else to offer. Another round of therapy yields a cure rate of less than 10%. Liver transplant can help, but there aren't enough livers to go around.

But the new study of 550 chronic HCV patients tried giving a low weekly dose of interferon.

At the end of the trial only 3.5% of subjects on interferon had suffered a severe HCV result, such as liver failure or death, vs. 7% for the control group.

Schering spokesman Robert Consalvo says that viewing HCV as a virus that can be lived with represents a paradigm shift.

"Currently there are no HCV therapies approved as maintenance therapies," he said. "But research is pointing us in that direction."

Still, some researchers continue to look for a better cure rate.

Small biotech InterMune (NasdaqNM:ITMN - News) presented a study that treated HCV nonresponders with its own interferon drug, Infergen, along with another interferon drug called Actimmune, which the firm now sells for a rare immunological disease.

After 48 weeks of treatment, 44% of patients' HCV was below the detection level.

InterMune Chief Executive Dan Welch says the poor response rate for interferon leaves room for tiny biotechs to make a move.

"We're not really fighting the giants of the hepatology world," said Welch. "We're letting them fight each other. After the patient has failed the first line of treatment, that's when we get involved."

Nonresponders also represent a growth market, he says. While the number of Americans infected with HCV remains stable, the appearance of interferon drugs in the last 10 years has started building up a growing pool of chronic sufferers whom they haven't cured. Welch says there are about 50,000 new nonresponders every year.

But drug makers both large and small are trying to move beyond interferon. Right now the hot area for HCV research is in protease inhibitors, related to the drugs now used to treat HIV (news - web sites).

Interferon works by boosting the patient's immune system, but not directly attacking the HCV.

Researchers hope protease inhibitors can stop the virus from replicating.

Schering, InterMune, and other firms -- including Vertex Pharmaceuticals (NasdaqNM:VRTX - News), Isis Pharmaceuticals (NasdaqNM:ISIS - News) and Rigel Pharmaceuticals (NasdaqNM:RIGL - News) -- are developing novel therapies. But none will hit the market sooner than six years out, and most will take longer.

Current attention, then, focuses on keeping patients alive until the new wave of drugs comes along. That means stretching the interferon therapies as far as they can go.

"It's important to optimize the currently available therapy," Schering's Consalvo said.

Those working in the industry remain optimistic about alternatives, however.

"For the first time, we don't have to wait till the next decade," Welch said. "We can do something for the growing list of patients who are basically marking time."

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Occult Hepatitis B in Dialysis Patients
http://www.eurekalert.org

Prevalence is higher than standard tests for hepatitis B would suggest

Some kidney dialysis patients contract hepatitis B virus (HBV) during the course of their treatment, possibly from other members of the dialysis population with occult HBV. People with occult HBV test negative for HBV surface antigen (HBsAg) but positive for HBV-DNA, which is detected through sensitive tests not typically performed on dialysis patients.

A recent study found that the prevalence of occult HBV in adult hemodialysis patients is four to five times higher than standard HBsAg testing would suggest. These findings are published in the November 2004 issue of Hepatology.

Hepatology , the official journal of the American Association for the Study of Liver Diseases (AASLD), published by John Wiley & Sons, Inc., is available online via Wiley InterScience (http://www.interscience.wiley.com
/journal/hepatology).

Previous studies that have looked for evidence of occult HBV in dialysis patients have found a wide range of infection rates – from 0 to 50 percent -- possibly due to the differences in the study populations. In this study, researchers, led by Dr. Gerald Y. Minuk of the University of Manitoba, sought to find the prevalence of occult HBV in a large North American population of adult dialysis patients and to determine if any demographic, biochemical and/or serologic feature could help identify those infected.

Between May and September of 2003, the researchers recruited hemodialysis patients in Winnipeg, Manitoba, an urban area in Canada with a population of about 680,000. They drew blood from and recorded demographic data for each of the 241 participants. They then performed liver biochemistry, HBV serology, and HBV-DNA testing by real-time polymerase chain reaction with two independent primer sets.

Only two of the participants tested positive for HBsAg, but an additional nine patients were found to have occult HBV, that is, they tested ne