Twice-Daily Interferon-Beta No Better Than Once-Daily Dosing for Hepatitis C

WESTPORT, CT (Reuters Health) Jul 03 - The antiviral effects of twice-daily administration of interferon-beta for the treatment of chronic hepatitis C infection are no greater in the long-run than once-daily administration, Japanese investigators report. However, those receiving therapy twice a day experience more severe side effects.

Dr. Fumitaka Suzuki, of Toranomon Hospital, in Tokyo, and associates randomly assigned 20 patients to receive twice-daily 3MU of interferon-beta or once-daily 6MU of interferon-beta for 4 weeks. "All patients received a further daily dose of 6MU interferon-beta for 12 weeks, followed by interferon-alpha three times a week for 16 weeks," they explain in the April issue of the Journal of Gastroenterology. All patients were infected with genotype 1b and exhibited high RNA levels.

Initially, the twice-daily regimen appeared to cause a more rapid fall in virus titer, with 8 of 10 patients in this group achieving viral RNA levels of less than 10,000 copies/mL during the first week. In contrast, only 2 of the 10 patients in the once-daily group achieved this degree of suppression.

However, the rate of disappearance of viral RNA did not differ significantly between the two groups. At 6 months after completion of therapy, one patient in the twice-daily group and none of the patients in the once-daily group achieved total viral elimination.

Dr. Suzuki's team also noted that proteinuria, thrombocytopenia, and elevation of ALT occurred more frequently among patients in the twice-daily group. Neither group of patients exhibited serum accumulation of interferon.

J Gastroenterol 2001;36:242-247.

Schering-Plough Announces FDA Approval to Market REBETOL(R) (Ribavirin, USP) Capsules Separately For Use in Combination With INTRON(R) A for Chronic Hepatitis C

KENILWORTH, N.J., July 26 /PRNewswire/ -- Schering-Plough Corporation (NYSE: SGP - news) today announced that the U.S. Food and Drug Administration (FDA) has granted marketing approval to REBETOL® (ribavirin, USP) Capsules as a separately marketed product for use only in combination with INTRON® A (interferon alfa-2b, recombinant) Injection for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with alpha interferon or who have relapsed following alpha interferon therapy. The safety and efficacy of REBETOL Capsules with interferons other than INTRON A have not been established.

REBETOL had been previously approved in the United States for this indication only as a component of REBETRON(TM) Combination Therapy, which contains REBETOL Capsules and INTRON A Injection in a single package. Schering-Plough will continue to market REBETRON Combination Therapy in the United States.

REBETOL Capsules, available by prescription only, are expected to be available nationwide sometime this fall.

REBETOL is an oral formulation of ribavirin, a synthetic nucleoside analog. Schering-Plough has exclusive worldwide rights to market oral ribavirin for hepatitis C through a licensing agreement with ICN Pharmaceuticals, Inc. (NYSE: ICN - news) of Costa Mesa, Calif.

INTRON A is a recombinant version of naturally occurring alpha interferon. Schering-Plough markets INTRON A, the world's largest-selling alpha interferon, for 16 major antiviral and anticancer indications worldwide.

It is not known how REBETOL and INTRON A work together to fight hepatitis C infection.

Warnings and Contraindications

REBETOL/REBETRON Combination Therapy

REBETOL monotherapy is not effective for the treatment of chronic hepatitis C and should not be used alone for this indication.

Anemia associated with REBETOL therapy may exacerbate cardiac disease that has lead to fatal and nonfatal myocardial infarctions. Patients with a history of significant or unstable cardiac disease should not be treated with REBETOL. It is advised that complete blood counts (CBC) be obtained at baseline and at weeks 2 and 4 of therapy or more frequently if clinically indicated.

REBETOL therapy must not be used by women, or male partners of women, who are or may become pregnant during therapy and during the 6 months after stopping therapy. REBETOL therapy should not be initiated until a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Women of childbearing potential and men must use effective contraception (two reliable forms) during treatment and during the 6-month post treatment follow-up period. Significant teratogenic and/or embryocidal effects have been demonstrated for ribavirin in all animal species in which adequate studies have been conducted. These effects occurred at doses as low as one twentieth of the recommended human dose of REBETOL. If pregnancy occurs in a patient or partner of a patient during treatment or during the 6 months after treatment stops, physicians are encouraged to report such cases by calling (800) 727-7064.

Alpha interferons, including INTRON A, cause or aggravate fatal or life- threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many but not all cases these disorders resolve after stopping INTRON A therapy.

The most common adverse experiences associated with combination REBETOL/INTRON A therapy are ``flu-like'' symptoms, such as headache, fatigue, myalgia, and fever, which appear to decrease in severity as treatment continues. Severe psychiatric adverse events, including depression, psychoses, aggressive behavior, hallucinations, violent behavior (suicidal ideation, suicidal attempts, suicides), and rare instances of homicidal ideation have occurred during combination REBETOL/INTRON A therapy, both in patients with and without a previous psychiatric disorder.

Schering-Plough is a research-based company engaged in the discovery, development, manufacturing and marketing of pharmaceutical products worldwide.

SOURCE: Schering-Plough Corporation

Roche Licenses Potential Second-Generation Drug From ICN to Set New Standards In Hepatitis C Treatment

BASEL, Switzerland, July 2 /PRNewswire/ -- Roche and ICN Pharmaceuticals, Inc. (NYSE: ICN - news) announced today that Roche has licensed in the rights to the developmental compound Levovirin, a promising second-generation drug for the treatment of hepatitis C from ICN.

Roche is currently developing Pegasys, its pegylated version of interferon alpha 2a, which on its own represents a major improvement in the treatment of hepatitis C. Its use in combination with Levovirin is expected to set new standards of care in this therapeutic area.

Levovirin is an L-isomer of ribavirin, which is part of current treatment regimes for hepatitis C. In preclinical studies, Levovirin shows immuno-modulatory activity similar to ribavirin but a better tolerability profile. Most importantly, the compound has not shown genotoxic effects in animals and cell-line studies and it does not seem to cause hemolytic anemia which is the major dose limiting side effect of ribavirin. Phase I clinical trials for the treatment of hepatitis C including Levovirin have been initiated in February 2001.

Levovirin will represent an important addition to Pegasys. The highest sustained virological response to therapy ever recorded for chronic hepatitis C patients has been achieved with combination therapy of Pegasys (40 kDa branched peginterferon alfa-2a) and ribavirin. The results from Phase III clinical trials were reported at the Digestive Disease Week in Atlanta, USA, in May this year. ICN also presented Levovirin's preclinical and development data at the same meeting.

``The incidence of hepatitis C is growing worldwide and physicians will require a range of highly effective therapies to treat this disease,'' said William M. Burns, head of the Pharmaceutical Division of Roche. ``We believe that Roche is strongly suited to meet the current and future demands of the marketplace and we see Levovirin as another important addition to our growing virology portfolio.''

Milan Panic, chairman and chief executive officer of ICN, said: ``We are pleased that Roche, a leading pharmaceutical company with its reputation for high-quality and innovative products, will assume responsibility for the development of Levovirin. Roche's worldwide marketing and distribution capabilities will enable physicians and their patients access to what we hope will prove to be a significant addition to the hepatitis C therapeutic arsenal.''

About the licensing agreement

Roche will pay a one-time licensing fee, milestone payments, and, after Levovirin has been successfully developed and received regulatory marketing clearance, royalties to ICN. Roche will be in charge of all future development activities and will have global marketing rights except for some Eastern European countries. Roche will also offer to ICN a compound at a similar stage of development.

About Hepatitis C

Hepatitis C is a potentially life-threatening viral infection that can lead to liver inflammation, liver disease, cirrhosis or liver cancer. Transmitted primarily through infected blood, approximately three percent of the world's population, or 170 million, is infected with the hepatitis C virus, making hepatitis C more common than the HIV virus. Chronic hepatitis C is the leading cause of liver transplantation today.

About ICN

ICN, headquartered in Costa Mesa, California, is an innovative-research focused global pharmaceutical company that manufacturers, markets and distributes a broad range of prescription and non-prescription pharmaceuticals under the ICN brand name. Its therapeutic focus is in anti-infectives, including anti-virals, dermatology and oncology.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world's leading research-oriented healthcare groups in the fields of pharmaceuticals, diagnostics and vitamins. Roche's products and services address prevention, diagnosis and treatment of diseases, thus enhancing well-being and quality of life. Roche has approximately 64,000 employees and sells its products in over 170 countries. In 2000 the Roche Group posted sales of 28,7 billion Swiss francs and an adjusted net income of 5,0 billion Swiss francs.

THE SAFE HARBOR STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995. This press release contains forward-looking statements that involve risks and uncertainties, including but not limited to, projections of future sales, operating income, returns on invested assets. Regulatory approval processes and other risks detailed from time to time in the company's Securities and Exchange Commission filings.

SOURCE: ICN Pharmaceuticals, Inc.

XTL Biopharmaceuticals Initiates Phase I Clinical Trial with XTL-002 for Hepatitis C

- Third Monoclonal Antibody in Clinical Development -

REHOVOT, Israel and NEW IPSWICH, N.H., July 3 /PRNewswire/ -- XTL Biopharmaceuticals Ltd. (LSE: XTL) today announced the commencement of Phase I clinical studies with XTL-002, its human monoclonal antibody (mAb) being developed for the treatment of hepatitis C virus (HCV) infections. The study, being conducted in Israel, is expected to enroll 15 patients and is designed to test safety, tolerability and changes in viral levels in chronic hepatitis C patients. The trial is being conducted following Food and Drug Administration (FDA, United States) and Ministry of Health (Israel) approvals.

XTL-002 is a fully human high-affinity monoclonal antibody which was shown to reduce viral levels of the HCV virus in XTL's proprietary in vivo model. The Company's HCV Trimera(XTL) model is being used in conjunction with a variety of corporate and academic partners to screen and evaluate novel compounds to treat HCV.

HCV is a major cause of chronic hepatitis in the United States and is a leading cause of liver transplantation. An estimated 4 million individuals are infected with HCV in the United States and the World Health Organization estimates that 170 million people are infected worldwide. Approximately 85% of HCV infected persons will develop chronic hepatitis, of which 20% will progress to liver cirrhosis. The number of deaths attributable to HCV is expected to triple in the next 10 to 20 years.

Martin Becker, Ph.D., President and Chief Executive Officer of XTL, said:

"This is our third monoclonal antibody and second clinical programme to enter human studies for the treatment of viral hepatitis, clearly establishing XTL as a leader in the discovery and development of therapeutics for these life-threatening chronic diseases."

Notes:

XTL Biopharmaceuticals develops novel therapeutics to treat life-threatening infectious diseases using fully human monoclonal antibodies and small molecule drugs. XTL's competitive advantage lies in its ability to leverage both its proprietary human tissue-based in vivo disease models and fully human monoclonal antibodies to validate and develop promising drug candidates. The Company's growing pipeline of therapies, designed to combat chronic viral infections, drug-resistant bacteria and serious systemic fungal infections, comprises internally developed products as well as those being co-developed with a number of biopharmaceutical partners. For more information about XTL, visit the Company's web site at www.xtlbio.com .

SOURCE XTL Biopharmaceuticals Ltd.

Hepatitis C Subtype Determines Interferon Responsiveness Factors

WESTPORT, CT (Reuters Health) Aug 14 - The factors that determine the responsiveness of the hepatitis C virus (HCV) to interferon treatment depend on the HCV subtype, according to a report in the August issue of Gut.

Because as few as 10% to 30% of patients treated with interferon show sustained responses with viral eradication, accurate prediction of response could spare considerable expense and toxicity from needless interferon therapy, the authors note.

Dr. I. Nakano from Nagoya University School of Medicine in Japan and colleagues took advantage of a newly identified subtype classification of HCV genotype 1b to explore predictive factors for interferon response.

Although genotype 1b patients overall responded to interferon treatment more poorly than genotype 2a patients, the authors report, genotype 1b patients with subtype W (distributed worldwide) or subtype J (found mainly in Japan) showed similar viral loads and interferon responsiveness.

Women with W-type virus experienced better interferon responses than did men with W-type virus, the report indicates, especially if they had low levels of HCV RNA. Among patients with J-type virus, interferon responsiveness was better when there was a history of blood transfusion, low levels of HCV RNA, or a mutated amino acid sequence in the region of the HCV genome that determines interferon sensitivity.

In a multivariate analysis, HCV RNA was the only significant predictor of interferon responsiveness overall, the investigators say, and neither genotype nor virus subtype was a significant independent factor.

"Combined analysis with several factors that were associated with interferon response may provide for more precise prediction of interferon response," the authors conclude.

Gut 2001;49:263-267.

Bio-Rad Enters New Territories for Hepatitis C Testing: Company Expands HCV License With Ortho/Chiron

HERCULES, Calif., Aug. 1 /PRNewswire/ -- Bio-Rad Laboratories, Inc. (Amex: BIO.A; BIO.B), a global leader in clinical diagnostics, announced today that it has been granted an expanded license for Hepatitis C Virus (HCV) tests by Ortho-Clinical Diagnostics (Ortho) and the Chiron Corporation (Chiron). This license amendment allows Bio-Rad to develop, manufacture and sell HCV immunoassay products to clinical diagnostics and blood bank virus laboratories in Asia (excluding Japan), South America and Central America. The new amendment also allows Bio-Rad to sell single-use, manual, and dip stick format HCV immunoassay products in the United States for research use and wellness assessment programs. Bio-Rad has been selling a selection of the same HCV tests in Europe and Africa under a license granted by Ortho and Chiron in 1993.

"This license amendment enables us to provide HCV tests to more laboratories throughout the world, and represents a very important development in our growth strategy in the blood virus diagnostics market," said Bio-Rad President David Schwartz.

Hepatitis C is a chronic virus that affects millions of people worldwide, and is the primary cause of liver failure and transplantation in the United States. Because patients can remain symptom-free for many years after infection, early testing can help detect and reduce the progression of the disease.

Bio-Rad has long been a leader in Hepatitis and HIV diagnostics, and also produces an array of other products used for medical screening and diagnosis. The company specializes in quality control systems, blood virus testing, toxicology, in vitro and genetic disorders testing, specialty chemistry, molecular pathology, and internet-based software. It is recognized worldwide as the "gold standard" in diabetes monitoring, broad-spectrum drug screening and hospital epidemiology.

Bio-Rad Laboratories, Inc. (www.bio-rad.com) is a multinational manufacturer and distributor of life science research products and clinical diagnostics. It is based in Hercules, California, and serves more than 70,000 research and industry customers worldwide through a network of more than 30 wholly owned subsidiary offices.

Various statements made within this press release may constitute "forward-looking statements" for purposes of the Securities and Exchange Commission's "safe harbor" provisions under the Private Securities Litigation Reform Act of 1995 and Rule 3b-6 under the Securities Exchange Act of 1934. The forward-looking statements contained herein involve risks and uncertainties that could cause results to differ materially from the Company's expectations.

SOURCE Bio-Rad Laboratories, Inc.

Three Rivers Pharmaceuticals Seeks Permission For Generic Treatment for Hepatitis C

PITTSBURGH, Aug. 24 /PRNewswire/ -- Three Rivers Pharmaceuticals, LLC, a Pittsburgh-based and privately-owned company, has filed an Abbreviated New Drug Application (ANDA) with the U.S. Food & Drug Administration (FDA) for permission to market the antiviral prescription drug ribavirin.

Ribavirin in combination with alpha interferon-2b is indicated for the treatment of Hepatitis C (HCV) and is marketed by Schering-Plough Corp.

Hepatitis C affects nearly four million Americans and an estimated 170 million people worldwide. HCV is responsible for an estimated 8,000 to 10,000 deaths per year and is the number one cause of liver transplants. HCV can also lead to cirrhosis, end-stage liver failure, and liver cancer. Over 30,000 new cases are diagnosed each year.

"Our mission," said Donald J. Kerrish, president of Three Rivers Pharmaceuticals, LLC, "is to develop and market generic prescription drugs, specifically antiviral medications used in the treatment of Hepatitis C and HIV/AIDS."

"By forging partnerships with international manufacturers of active pharmaceutical ingredients and utilizing contract research manufacturers and contract research organizations located in the United States, Three Rivers Pharmaceuticals can develop, seek FDA approval, and market generic drugs faster and less expensively than its competitors," according to Kerrish.

"We are concentrating our resources," added Kerrish, "on developing lower cost generic drugs for infectious diseases that have a significant national and worldwide impact with the goal of pricing them as aggressively as possible. We also will provide public education and disease state management programs for Hepatitis C and HIV/AIDS."

SOURCE Three Rivers Pharmaceuticals, LLC

Daily High-Dose Interferon Induction Therapy Not Advantageous in Hepatitis C

WESTPORT, CT (Reuters Health) Sept 03 - Initial induction treatment with daily high-dose lymphoblastoid interferon (IFN) alpha-n1 appears to be no better than the standard interferon regimen for chronic hepatitis C, Spanish researchers report in the August issue of the Journal of Medical Virology.

Dr. Vicente Carreno from the Fundacion para el Estudio de la Hepatitis Virales, Madrid, and colleagues randomly assigned 155 patients with hepatitis C to one of three treatment groups.

Patients in group 1 received initial daily induction with 10 MU of IFN alpha followed by 1 month of rest, while patients in group 2 received the same regimen but without a 1 month rest period. After initial therapy, patients in groups 1 and 2 were given 10 MU IFN alpha three times a week for 2 months followed by 5 MU for 2 months and 3 MU for 8 months. Patients in group 3 received standard therapy with 5 MU IFN alpha three times a week for 2 months followed by 3 MU for 11 months, the researchers report.

Sustained ALT responses were not statistically significantly different among patients treated with daily IFN alpha induction compared with those who received standard therapy on an intention-to-treat analysis, Dr. Carreno's group found.

This trend was also true for HCV RNA concentrations, which were reduced in groups 1 and 2 compared with group 3, but this difference too was not statistically significant.

"Taken together, the results suggest that induction therapy is not better in comparison with standard therapy for the treatment of chronic hepatitis C, at least at IFN alpha-n1 doses and schedule used," Dr. Carreno and colleagues conclude.

J Med Virol 2001;64:460-465.

Peginterferon Regimen Outperforms Standard Treatment for Chronic Hepatitis C

WESTPORT, CT (Reuters Health) Sept 20 - Interferon alfa-2b plus ribavirin therapy is now the standard initial treatment for patients with chronic hepatitis C, but a report published in the September 22nd issue of The Lancet indicates that a peginterferon-based regimen achieves higher sustained virologic response (SVR) rates.

Previous studies have shown that peginterferon can achieve SVR rates that are twice that of standard interferon. However, relapse rates are high with peginterferon monotherapy and most patients with hepatitis C virus (HCV) genotype 1 infection, the most common and difficult to treat form of infection, do not achieve SVR.

In the current study, Dr. Michael P. Manns, from the Medizinische Hochschule in Hannover, Germany, investigated the effects of peginterferon alfa-2b in combination with ribavirin on viral suppression. Based on findings with standard interferon therapy, the researchers were hopeful that adding ribavirin to the peginterferon regimen would reduce the relapse rate.

The study included 1530 patients with chronic hepatitis C who were randomized to receive 3 MU of interferon subcutaneously three times a week, or 1.5 or 0.5 micrograms/kg per week of peginterferon. Subjects also received non-weight-adjusted daily doses of ribavirin. Twenty-four weeks after the 48-week treatment course, the patients' serum was analyzed for the presence of HCV RNA.

The higher dose peginterferon group had a SVR rate of 54%, significantly higher than the 47% rate found in each of the other groups, Dr. Manns told Reuters Health. "The benefits of the higher dose regimen were most apparent for patients infected with the HCV genotype 1," he noted.

"Based on intention-to-treat analysis, the SVR rate for patients with genotype 2 and 3 was about 80% for each of the regimens," Dr. Manns said. "However, if you consider only patients who completed the full treatment course, the rate is closer to 90%."

Dr. Manns pointed out that further analysis revealed that the SVR rate associated with the higher dose regimen would have been even higher if the ribavirin had been dosed according to weight.

Dr. Mann predicts that "peginterferon plus ribavirin will become the standard treatment for chronic hepatitis C." Not only is it more effective than standard interferon therapy, "but it also is given just once a week as opposed to three times a week," he added.

Lancet 2001;358:958-965.

Copyright © 2001 Reuters Ltd.

Some Blood Donors Get Bad News

By ERIN McCLAM
.c The Associated Press

ATLANTA (AP) - Some Americans who rushed to donate blood for strangers hurt in the terrorist attacks will get a very personal shock - news that traces of disease have turned up in their contributions.

Two weeks after the suicide hijackings, the first letters and phone calls are going out to donors whose blood was rejected because tests detected HIV, hepatitis or other infectious agents.

For people who only wanted to help, the news can be devastating.

``They're really at a loss. Some of them are sobbing when they're calling,'' said Thelma King Thiel, chief executive of Hepatitis Foundation International, which has taken calls from blood donors surprised to learn they have the dangerous virus.

Donated blood is screened for HIV, hepatitis B and C, syphilis and other antigens. Because of the risk of false-positive results, blood that raises flags is sent through more tests to confirm the infections.

That work generally takes several days. But contacting the infected donors - standard practice for blood banks - takes longer, especially amid the crush of donations that followed the Sept. 11 attacks.

Many of those donors were giving for the first time. At the National Institutes of Health, 65 percent of people who gave blood in the days after the attacks were first-time donors, said Dr. Harvey Klein, director of blood banks for NIH.

First-time donors, also called volunteer donors, are generally healthy people who tend to avoid high-risk activities, like injection drug use.

They also usually don't otherwise seek blood tests - which can make the shock of finding out their blood is tainted all the worse.

``The person that comes to donate blood is a very special person. It's somebody that is very conscious of his or her community,'' said Dr. Celso Bianco of America's Blood Centers, an association of independent blood banks. ``It's very difficult for them.''

The blood banks share positive test results with donors but keep them otherwise confidential.

Volunteer donors may also not be familiar with infectious diseases for which they test positive. So blood banks either have staff counselors or refer donors to community groups that can help them cope.

``Everybody's so frightened and fearful,'' said Thiel, of the hepatitis foundation. ``They probably had no signs or symptoms. Some of them think they're going to die.''

HIV, the virus that causes AIDS, shows up in only one of every 50,000 to 200,000 donations, Bianco said. Hepatitis is slightly more common, showing up in one donation out of 10,000 to 50,000, depending on the type of virus, he said.

Still, blood-bank counselors are bracing to help more people because of the sheer volume of attack-related blood donations.

``These are people who come in to do something good, and instead of being able to do something good, we're going to tell them something bad,'' Klein said. ``It's a very delicate situation.''

On the Net:

Hepatitis Foundation International: http://www.hepfi.org

Myriad Genetics Discovers Novel Hepatitis 'C' Target; Drug Development Program H

SALT LAKE CITY, Sept. 6 /PRNewswire/ -- Myriad Genetics, Inc. (Nasdaq: MYGN) has discovered a novel drug target for the treatment of human infection by the hepatitis C virus (HCV), and has initiated high-throughput screening with its ProTrap(TM) drug screening technology, the Company announced today. The HCV target was discovered using Myriad's ProNet(R) proteomics technology to investigate the viral-human protein interactions that allow the virus to replicate after commandeering the human cellular machinery.

The drug target is a protein that, Myriad believes, has not been explored previously for drug development, and represents a totally new approach to the problem of treating viral diseases. The HCV target was discovered by following a similar therapeutic target discovery strategy that had been applied successfully by Myriad in the identification of drug targets in HIV and hepatitis B virus (HBV).

"Myriad's drug development pipeline has had a strong oncology focus and is strengthened by an exciting viral disease program as we advance our HIV, HBV and HCV programs," said Dr. Adrian Hobden, President of Myriad Pharmaceuticals, Inc. "We believe we will be a significant future force in the treatment and prevention of cancer and viral diseases, and will also play an important role in other common diseases, including inflammatory and central nervous system diseases."

The addition of this new HCV drug target raises Myriad's total to 141 active drug targets. These targets are derived from the analysis of over 1,000 novel proteins with Myriad's ProNet(R) pathway technology. High- throughput screening has been initiated on 56 drug targets. Drug targets in high-throughput screening are from the disease fields of cancer, heart disease, central nervous system diseases, diabetes, inflammatory disease and viral infection. Myriad has 36 drug candidates under study and 12 advanced drug development programs.

Hepatitis C is a blood-borne virus that was previously referred to as non- A/non-B hepatitis. The NIH estimates that 4 million Americans are infected with HCV, and as many as 400 million worldwide. The virus enters the body through direct blood exposure and attacks and kills liver cells where it multiplies. This process causes inflammation in the liver and results in the death of liver cells. The incubation period varies from two weeks to six months. It is believed that as many as 85% of people initially infected with HCV become chronically infected. The disease will then progress over a period of years with some individuals sustaining liver damage that will lead to cirrhosis and/or liver cancer and may require liver transplants.

Myriad Genetics, Inc. is a leading biopharmaceutical company focused on the development of novel healthcare products. The Company has established two wholly owned subsidiaries. Myriad Pharmaceuticals, Inc. develops and intends to market therapeutic products, and Myriad Genetic Laboratories, Inc. develops and markets proprietary predictive medicine and personalized medicine products. The Company has established strategic alliances with Bayer, Eli Lilly, Hitachi, Novartis, Oracle, Pharmacia, Roche, Schering AG, Schering- Plough and Syngenta.

The discussion in this news release includes forward-looking statements that are subject to certain risks and uncertainties including statements relating to the Company's future role in the treatment and prevention of diseases. Such statements are based on management's current expectations that are subject to risks and uncertainties that could cause future results to differ materially from those set forth in or implied by forward-looking statements, including but not limited to: intense competition related to the discovery and development of therapeutics; uncertainties as to whether the Company and its collaborators will be successful in developing, and obtaining regulatory approval for, and commercial acceptance of, therapeutics; uncertainties as to the Company's ability to develop therapeutic compounds, which is a new business area for the Company; and the risk that markets will not exist for therapeutic compounds that the Company develops or if such markets exist, that the Company will not be able to sell compounds, which it develops, at acceptable prices. All information in this press release is as of September 6, 2001, and Myriad undertakes no duty to update this information unless required by law.

Quick Treatment Can Cure Hepatitis C

By DANIEL Q. HANEY
.c The Associated Press

BOSTON (AP) - Quick treatment after infection can almost always cure hepatitis C, a condition that causes between 8,000 and 10,000 deaths in the United States each year, according to a study released Monday.

The study found that the medicine, interferon A, can eliminate all traces of the virus, but it must be given soon after the earliest symptoms of the virus appear.

The approach may have limited practical effect, because early-stage infection is hard to spot. Most people do not immediately realize they have caught the virus, because the initial symptoms are often mild flu-like ills, such as muscle ache and poor appetite.

However, for those who begin treatment within two or three months of contracting hepatitis C, the treatment appears to be virtually 100 percent effective in getting rid of the virus.

``This study may make people aware of how important it is to diagnose hepatitis C,'' said Dr. Michael P. Manns, a co-author of the study at Hannover Medical School in Germany.

Treatment now often begins after people have carried the virus for many years. The standard in those cases is a combination of interferon A and the antiviral drug ribavirin, which eliminate the virus about half the time.

In an effort to see if earlier treatment would work better, the researchers asked physicians to be alert for early cases and enroll patients in the study. Doctors at 24 hospitals in Germany identified 44 cases this way.

``If somebody is indeed diagnosed with hepatitis C, this is important,'' said Dr. Adrian Di Bisceglie, medical director of the American Liver Foundation. ``It says if you treat them early enough, you get rid of the infection in everybody, and that's fairly dramatic.''

The results are scheduled to be published in the Nov. 15 issue of the New England Journal of Medicine. Because of their importance, the results were released Monday on the journal's Web site.

The study was financed by Essex-Pharma, which makes the interferon.

Hepatitis C is usually spread by contact with infected blood. In the latest study, most of the patients caught it through drug abuse, accidental needle jabs in hospitals or surgery.

They started therapy within an average of 89 days of catching hepatitis C. The patients received daily interferon injections for four weeks, then three times a week for 20 more weeks. Forty-eight weeks after the study began, the virus was undetectable in all but one patient.

About 4 million people in the United States and 170 million worldwide are estimated to be infected with hepatitis C. The infection has become much less common since 1991, when blood banks began screening for the virus. Still, hepatitis C infection is the leading cause of chronic liver disease in the United States and the most frequent reason for liver transplants.

Leslie Johnson, a researcher at the National Institute of Allergy and Infectious Diseases, estimated that about 15,000 Americans will catch hepatitis C this year. Sixty percent with be injection drug abusers.

Medical Editor Daniel Q. Haney is a special correspondent for The Associated Press.

On the Net:

Journal: http://content.nejm.org/

Drug May Limit Liver Damage Caused by Hepatitis C

By Gene Emery

BOSTON (Reuters) - Researchers reported on Monday they may have found a way to prevent lasting liver damage in virtually every case of hepatitis C as long as treatment can begin during the earliest stages of the potentially fatal infection.

The report, which could affect the treatment of hundreds of millions of people infected with the virus, will appear in the Nov. 15 issue of the New England Journal of Medicine (news - web sites). But the editors released the findings six weeks early because of the clinical implications.

A team led by Dr. Elmar Jaeckel of the Hannover Medical University in Hannover, Germany, found they were able to prevent the development of chronic hepatitis C in 44 volunteers who were aggressively treated with injections of interferon alfa-2b while they were suffering from acute hepatitis C, the short-term version of the illness.

In all but one case, daily interferon injections reduced the amount of hepatitis C virus (HCV) in the blood to undetectable levels.

``We found that early treatment with acute hepatitis C with interferon alfa-2b alone prevented the development of chronic HCV infection in almost all patients'' said the researchers. Anyone with acute hepatitis C should receive the drug, they said.

Dr. Michael Manns of Hannover, a co-author of the study, told Reuters the findings should encourage doctors to be more vigilant about identifying cases of acute hepatitis now that it is known that early treatment can prevent the development of long-term illness.

``Everyone should be alert to diagnosing acute hepatitis C,'' he said.

Nearly 4 million people in the United States and 170 million worldwide are believed to be infected with the hepatitis C virus. Long-term infection is the leading cause of liver disease in the United States and, once it causes liver failure, the leading cause of liver transplants.

Hepatitis C usually comes from sharing needles or through unprotected sex, although some infections can be traced to a transfusion of contaminated blood. Blood banks now have screening tests for the virus.

Symptoms may include fever, fatigue and nausea, but many people who develop an acute hepatitis C infection do not realize it. Yet in 50 to 84 percent of the cases, the acute infection progresses to chronic hepatitis C, a process that can take up to 20 years, according to the Jaeckel team and epidemic.org, a Dartmouth College Web site on hepatitis.

The researchers gave daily injections of interferon to volunteers for the first four weeks of therapy. They received the drug three times a week for the remainder of the study.

The doctors found that, on average, HCV had dropped to undetectable levels after about 3.2 weeks of treatment. After two years, only one of the 44 patients had any trace of the virus in their blood.

In a similar group of 40 untreated patients, chronic hepatitis C developed in 28.

``Since the current treatment for chronic HCV infection eliminates the virus in only about half the cases,'' the researchers said, ``we suggest that all patients with acute hepatitis C should be treated'' with interferon.

PRICE OF "UNBUNDLED" REBETOL (RIBAVIRIN) FOR THE TREATMENT OF HEPATITIS C

October 8, 2001

Community Notice

On October 3, Schering-Plough Corporation announced that the company was shipping separately packaged (unbundled) Rebetol (ribavirin) capsules to pharmacies for the treatment of chronic hepatitis C virus (HCV) infection in combination with alfa-interferon. The company's announcement did not include Rebetol's price.

The average wholesale price (AWP) of Rebetol, a nucleoside analogue, is $1,102/month for the 800mg/day dose and $1,653/month for the 1,200mg/day dose. This is a 52% increase over the price of the same Rebetol included in Rebetron (Intron A + Rebetol combination kits). Of note, the cost of Rebetol (1,200mg) alone is more than the cost of a Rebetron kit ($1,511/month), which contains the same amount of Rebetol. The Rebetol price is also much higher than that of the highest priced HIV nucleoside analogue on the market, Ziagen ($385/month).

A drug price comparison table is listed below and is in attachment. If these do not display or print out well the table will be posted on website for Hepatitis Support Project at www.hcvadvocate.org.

Early this year, Schering-Plough's PEG-Intron (pegylated interferon alfa-2b) was priced 127% higher than the company's standard interferon (Intron A). If common doses of PEG-Intron and Rebetol are used, the cost of HCV treatment for one patient will increase from $18,000 to approximately $25,000 per year.

Compounded ribavirin is still available for patients, healthcare providers, and payers to consider. Compounding pharmacies throughout the country provide ribavirin at about $150-$225/month for 800-1,200mg/day dose. Two generic companies have applied to the FDA to manufacture ribavirin, but generic manufacture is currently being challenged in court by Schering-Plough, which could delay the availability of generic ribavirin for up to 30 months

We provide this information so that patients, healthcare providers, and payers can make informed choices in their own cost-benefit analyses of Rebetol versus compound ribavirin and Peg-Intron versus standard interferon.

Contact:

Brian D. Klein, HAAC/SF
Email: HAAC_SF@hotmail.com

James Learned, HAAC/NY
Email: James_Learned@prodigy.net

HAAC receives no money from any pharmaceutical company or pharmacy. Our goal is to help folks like us in the HCV community make informed choices and have the access and flexibility to choose the treatment that will best meet their individual needs. -----------------------------------------------------------------------

DRUG PRICE COMPARISON (Figures obtained for commonly used doses October 5, 2001)

        Average Wholesale Price(AWP)

Medication    Brand    per month    per year

HIV Nucleoside Analogues
zalcitabine(ddC)    Hivid    $260    $3,120
lamivudine(3TC)    Epivir    286    3,424
didanosine(ddI enteric coated)        287    3,444
stavudine(d4T)    Zerit    311    3,732
zidovudine (AZT)    Retrovir    334    4,008
abacavir    Ziagen    385    4,620
 

HCV Nucleoside Analogue
ribavirin(800/1200mg)    (compounded)    150/225    1,800/2,700
ribavirin(1200mg)    Rebetol(in Rebetron kits)    1,085    13,020
ribavirin(800/1200mg)    Rebetol(separate sale)    1,102/1,653    13,224/19,836
 

HCV Immune Modulators
interferon a-2b,(3MIU)    Intron A    426    5,112
PEG-interferon a-2b(120ug)    PEG-Intron    965    11,580
 

HCV Combination Treatments
IFNa-2b+ribavirin(1200mg)(separate/compounded)        651    7,812
PEG-Intron+ribavirin(800mg)(compounded)        1,115    13,380
 

IFNa-2b+Rebetol(1200mg)    Rebetron    1,511    18,132
PEG-Intron+Rebetol(800mg)    (separate sale)    2,067    24,804
 

HEPATITIS C ACTION & ADVOCACY COALITION (HAAC)
53 Divisadero Street
San Francisco, CA 94117

Genetic tinkering turns back cirrhosis

By Randy Dotinga
HealthScoutNews Reporter

MONDAY, Oct. 29 (HealthScoutNews) -- When people think of scars, the first things that usually come to mind are the marks of old injuries on the skin. But traumatized internal organs can scar too, wreaking havoc on the inner workings of the body. For several years, scientists have been trying to find ways to stop and even reverse excessive scarring. Now, American and British researchers say they are close to figuring out how to do that for patients with cirrhosis, an often fatal liver disease characterized by scarring. If successful, the treatment may help patients with severe burns, cystic fibrosis and other ailments.

The key is reprogramming a protein whose job is to make scarring happen. "It's a completely different approach, not just another antibiotic," says Dr. Mario Chojkier, co-author of a new study and professor of medicine at the University of California at San Diego.

Liver disease and cirrhosis are the 10th leading killer of Americans. While cirrhosis is closely connected to alcoholism -- an estimated half of men who drink more than eight drinks a day will develop the ailment -- it's also caused by hepatitis and other diseases.

As liver disease progresses, toxins poison the organ and cause scar tissue to build up, blocking blood vessels that travel through it. "It's like clogging a pipe. It makes the blood flow go backwards, which will have major consequences. Things that are good or bad for the body can't be handled accordingly by the liver because the blood can't reach it," Chojkier says.

Other problems can develop, like yellowish skin (known as jaundice), bleeding and liver failure.

While doctors can try to stop the causes of cirrhosis, they haven't been able to turn back time on scarring. "We have to accept that we cannot treat everybody. That's why we need alternatives," says Dr. Adrian Di Bisceglie, medical director of the American Liver Foundation.

That's where the U.S. and U.K researchers come in. Their findings appear in the Oct. 26 issue of the medical journal Molecular Cell.

By tinkering with the genetics of a protein so that it no longer has an amino acid that starts an excessive scarring process, they have changed the way scars develop in mice with liver disease.

Existing scar tissue may even evaporate, a process called "melting" by some researchers. "It could get back to normal little by little," Chojkier says.

Experiments on humans may come in the next several years. With luck, the new treatment "could be utilized for the prevention of fibrosis [scarring] in other organs, like the lungs and kidney and skin and the brain. We think if it works in one organ, it has a very good chance of working in another," Chojkier says.

Liver disease experts say the new research is intriguing, but they caution that successful research in mice doesn't always translate to human treatments.

The findings are part of a "growing body of information and excitement" in the medical community about the prospects of stopping and reversing scarring, says Dr. Scott Friedman, professor of medicine at Mt. Sinai School of Medicine.

Even without the new research, doctors can do much more for liver disease patients than in the recent past, Di Bisceglie says. "If you go back 10 or 15 years ago, we had very few treatments. In the last 10 years, we've seen a lot of developments like liver transplants, which we do 4,000 to 5,000 times a year in this country. There are treatments that are increasingly effective."

What To Do

Read about the basics of cirrhosis from Hepatitis Foundation International.

Maxim Pharmaceuticals to Initiate Phase 2 Clinical Trial of Ceplene in Triple Combination Therapy for Hepatitis C

SAN DIEGO--(BW HealthWire)--Nov. 1, 2001--Maxim Pharmaceuticals (Nasdaq:MAXM - news; SSE:MAXM) today announced details of its upcoming Phase 2 trial of its product candidate Ceplene(TM) (histamine dihydrochloride) in triple combination therapy for the treatment of patients infected with hepatitis C who failed to respond to prior therapy.

The randomized, controlled Phase 2 study is designed to compare the treatment of nonresponder hepatitis C patients with a triple-drug combination of Ceplene and Schering Corp.'s Peg-Intron® (peginterferon alfa-2b) and Rebetol® (ribavirin, USP) versus treatment with Peg-Intron and Rebetol combination therapy alone. The study is expected to enroll up to a total of approximately 280 patients with hepatitis C who failed to respond to prior therapy with the combination of interferon-alpha and ribavirin. The primary measures of efficacy in the study will be viral response, biochemical response (normalization of the liver enzyme ALT, a standard measure of liver function) and histological improvement measured from tissue biopsies. Nonresponder patients represent the largest current unmet need for treatment in Hepatitis C.

The study is currently planned to commence in Europe and Israel before the end of 2001. Maxim is the sponsor of the trial and will be solely responsible for conducting the study. Maxim also announced that it has entered into an agreement under which Schering Corp. will contribute the Peg-Intron and Rebetol product and perform the viral testing for the study at no cost to Maxim.

``This new trial targets a patient population with an important unmet need, and is designed to be the first step in more advanced testing of Ceplene in combination with pegylated interferon and ribavirin,'' said Kurt R. Gehlsen, Maxim's senior vice president, development and chief technical officer.

Maxim also announced that it and F. Hoffmann - La Roche Ltd. and Hoffmann - La Roche Inc. have terminated their collaboration agreement. However, Maxim and Roche both continue to cooperate and participate in the multi-national clinical study, the ``Dynamically Individualized Treatment of Hepatitis C Infection and Correlates of Viral/Host Dynamics'' study (``DITTO-HCV''), currently underway.

Hepatitis C Overview

Hepatitis C is more easily transmitted than HIV and is now the leading blood-borne infection in the United States. The U.S. Center for Disease Control and Prevention estimates that over 4.5 million Americans are infected with the hepatitis C virus. The World Health Organization and other sources estimate that more than 200 million people are infected worldwide.

Hepatitis is a disease characterized by inflammation of the liver and, in many cases, permanent cirrhosis (scarring) of the liver tissues and mortality. The progress of the disease from infection to significant liver damage can take 20 years or more. Some experts estimate that without substantial improvements in treatment, deaths from hepatitis C will surpass those from HIV. Hepatitis C is the leading cause of liver cancer and the primary reason for liver transplantation in many countries.

Ceplene and Maxim Overview

Maxim Pharmaceuticals is a global biopharmaceutical company with a diverse pipeline of product candidates for life-threatening cancers and hepatitis. Maxim's research and development programs are designed to provide hope to patients most in need by developing safe and effective product candidates that extend survival while maintaining quality of life. Maxim has attracted an experienced international management group and a team of employees dedicated to commercializing life-enhancing product candidates. Joining this motivated team in its mission are world-leading scientific and clinical investigators and major pharmaceutical development partners.

Ceplene, based on the naturally occurring molecule histamine, is designed to prevent or inhibit oxidative stress, thereby reversing immune suppression and protecting critical immune cells. Ceplene is administered in combination with cytokines such as interleukin-2 or interferon-alpha, a class of proteins that stimulate these same immune cells.

Ceplene is currently being tested in Phase 3 cancer clinical trials for advanced metastatic melanoma and acute myelogenous leukemia. Phase 2 trials of Ceplene are also underway for the treatment of hepatitis C and advanced renal cell carcinoma. More than 1,300 patients have participated in the company's completed and ongoing clinical trials. Ceplene is an investigational drug and has not been approved by the U.S. Food and Drug Administration or any international regulatory agency.

Maxim is also developing small-molecule inhibitors and activators of programmed cell death, also known as apoptosis, that may serve as drug candidates for cancer, cardiovascular disease and other degenerative diseases. Lastly, the company's MaxDerm technology is designed for the treatment of medical conditions for which topical therapy is appropriate such as oral mucositis, herpes, decubitus ulcers, shingles, burns and related conditions.

This news release contains certain forward-looking statements that involve risks and uncertainties. Such forward-looking statements include statements regarding the efficacy and intended utilization of Ceplene, the apoptosis modulator compounds and MaxDerm, and regarding the Company's clinical trials. Such statements are only predictions and the Company's actual results may differ materially from those anticipated in these forward-looking statements. Factors that may cause such differences include the risk that products that appeared promising in early research and clinical trials do not demonstrate safety or efficacy in larger-scale clinical trials, the risk that the Company will not obtain approval to market its products, the risk that clinical trials may not commence when planned, and the risks associated with the dependence upon collaborative partners. These factors and others are more fully discussed in the Company's periodic reports and other filings with the Securities and Exchange Commission.

Note: Ceplene(TM), MaxDerm(TM) and the Maxim logo are trademarks of the Company.

Editor's Note: This release is also available on the Internet at http://www.maxim.com.

--------------------------------------------------------------------------------

Maxim Reports Results From Hepatitis C Pilot Study of Ceplene Triple-Drug Therapy At AASLD Conference

Researchers Make Three Presentations Regarding Ceplene at the 52nd American Association for the Study of Liver Disease (AASLD) Conference

SAN DIEGO--(BUSINESS WIRE)--Nov. 12, 2001-- Maxim Pharmaceuticals (Nasdaq:MAXM - news; SSE:MAXM) announced that 72-week results were presented yesterday from its completed pilot study evaluating Ceplene(TM) (histamine dihydrochloride) in combination with interferon-alpha (IFN-alpha) and ribavirin in the treatment of chronic hepatitis C patients who were nonresponsive to previous therapy.

The study is one of three Ceplene presentations being made by independent researchers at the 52nd meeting of the American Association for the Study of Liver Diseases (AASLD) in Dallas. The results from the completed studies described in the three presentations provide the foundation for the more advanced clinical testing of Ceplene in hepatitis C planned to commence before the end of the year.

In the study, chronic hepatitis C patients who did not respond to or relapsed from previous therapy were treated for 48 weeks with the Ceplene/IFN-alpha/ribavirin triple-drug combination, and followed for an additional 24 weeks after completion of therapy. At 72 weeks, sustained complete viral response was observed in 28 percent (5/18) of patients who entered the study, and in 38 percent (5/13) of evaluable patients (patients who completed at least four weeks of therapy). A complete viral response was defined by virus levels that are below the limit of detection using a validated PCR-RNA technique (Cobas Amplicor HCV Monitor(TM) Test). No serious adverse events and no unexpected or irreversible side effects were reported in the Ceplene study.

The results were presented yesterday at the AASLD conference by Yoav Lurie, M.D., principal investigator in the study and head, Hepatitis Clinic, Liver Unit, Institute of Gastroenterology and Hepatology, Tel Aviv Souraski Medical Center, Israel. Patients that have failed prior therapy for hepatitis C represent a substantial population in need of more effective treatments.

``This study met its objective by demonstrating that Ceplene can be safely administered in this triple-drug combination, and clearly shows that this triple-drug therapy is feasible in nonresponder patients,'' said Dr. Lurie. ``Although this study was not designed to demonstrate efficacy due to the small number of patients involved, the end-of-study results are promising and I look forward to more advanced studies.''

Dr. Lurie will also present today previously reported results from a 129-patient Phase 2 study evaluating the treatment of therapy-naive, chronically infected hepatitis C patients with the combination of Ceplene and IFN-alpha. In the study, 40 percent of evaluable hepatitis C patients treated with the combination of Ceplene and IFN-alpha achieved a sustained complete viral response at 72 weeks. Published research suggests a 16 percent sustained complete response commonly observed for patients treated with IFN-alpha alone.

In addition, Avidan Neumann, Ph.D., Bar-Ilan University, Ramat-Gan, Israel, will make a presentation today at the AASLD conference related to the 129-patient Phase 2 study entitled ``Early Hepatitis C Viral Kinetics During Combination Therapy with Histamine Dihydrochloride and Interferon-Alpha and its Prediction of Sustained Viral Response.'' The presentation will show that an early rapid viral response for patients treated with the Ceplene/IFN-alpha combination was achieved in 63 percent of patients with the genotype 1 variant of the virus and in 76 percent of patients with the genotype 2 /3 variants of the virus. Dr. Neumann's report concludes that these early rapid viral response rates are higher than those commonly reported for treatment with either IFN-alpha or the combination of IFN-alpha and ribavirin.

``The data emerging from the two clinical trials reported at this important liver disease conference supports our further development plans for Ceplene,'' said Kurt R. Gehlsen, Ph.D., Maxim's senior vice president, development and chief technical officer. ``Ceplene has shown a broad potential in different hepatitis C-infected patient populations using multiple treatment regimens. We look forward to combining Ceplene with the current standard of care, pegylated interferon and ribavirin, in our upcoming Phase 2 triple-drug study in nonresponder patients.''

The company recently announced that it plans to commence this fall a 280-patient randomized, controlled, triple-drug Phase 2 trial of Ceplene in combination with pegylated interferon (peginterferon alfa-2b) and ribavirin for the treatment of patients infected with hepatitis C who failed to respond to prior therapy.

Ceplene is an investigational drug and has not been approved by the U.S. Food and Drug Administration or any international regulatory agency.

Hepatitis C Overview

Hepatitis C is now the leading blood-borne infection in the United States. The U.S. Center for Disease Control and Prevention estimates that over 4.5 million Americans are infected with the hepatitis C virus. The World Health Organization and other sources estimate that more than 200 million people are infected worldwide.

Hepatitis is a disease characterized by inflammation of the liver and, in many cases, permanent cirrhosis (scarring) of the liver tissues and mortality. The progress of disease from infection to significant liver damage can take 20 years or more. Some experts estimate that without substantial improvements in treatment, deaths from hepatitis C will surpass those from HIV. Hepatitis C is the leading cause of liver cancer and the primary reason for liver transplantation in many countries.

Ceplene and Maxim Overview

Maxim Pharmaceuticals is a global biopharmaceutical company with a diverse pipeline of therapeutic candidates for life-threatening cancers and hepatitis. Maxim's research and development programs are designed to offer hope to patients by developing safe and effective therapeutic candidates that extend survival while maintaining quality of life. Maxim has attracted an experienced international management group and a team of employees dedicated to commercializing life-enhancing product candidates. Joining this motivated team in its mission are world-leading scientific and clinical investigators and major pharmaceutical development partners.

Ceplene, based on the naturally occurring molecule histamine, is designed to prevent or inhibit oxidative stress, thereby reversing immune suppression and protecting critical immune cells. Ceplene is administered in combination with cytokines such as IFN-alpha and interleukin-2, a class of proteins that stimulate these same immune cells.

Ceplene is currently being tested in Phase 3 cancer clinical trials for advanced metastatic melanoma and acute myelogenous leukemia. Phase 2 trials of Ceplene are also underway for the treatment of hepatitis C and advanced renal cell carcinoma. More than 1,300 patients have participated in the Company's completed and ongoing clinical trials.

Maxim is also developing small-molecule inhibitors and activators of programmed cell death, also known as apoptosis, that may serve as drug candidates for cancer, cardiovascular disease and other degenerative diseases. Lastly, the Company's MaxDerm technology is designed for the treatment of medical conditions for which topical therapy is appropriate such as oral mucositis, herpes, decubitus ulcers, shingles, burns and related conditions.

This news release contains certain forward-looking statements that involve risks and uncertainties. Such forward-looking statements include statements regarding the efficacy and intended utilization of Ceplene, the apoptosis modulator compounds and MaxDerm, and regarding the company's clinical trials. Such statements are only predictions and the company's actual results may differ materially from those anticipated in these forward-looking statements. Factors that may cause such differences include the risk that products that appeared promising in early research and clinical trials do not demonstrate safety or efficacy in larger-scale clinical trials, the risk that the company will not obtain approval to market its products, the risk that clinical trials may not commence when planned, and the risks associated with the dependence upon collaborative partners. These factors and others are more fully discussed in the company's periodic reports and other filings with the Securities and Exchange Commission.

Note: Ceplene(TM), MaxDerm(TM) and the Maxim logo are trademarks of the company.

Editor's Note: This release is also available on the Internet at http://www.maxim.com.

--------------------------------------------------------------------------------

Contact:

DALLAS, Nov. 12 /PRNewswire/ -- BioMedicines, Inc. today announced positive results from two Phase II clinical trials employing the company's omega interferon for the treatment of patients chronically infected with the hepatitis C virus (HCV). The results from clinical trials conducted at the Scripps Institute in the United States, as well as interim findings from a larger European multicenter clinical trial, were presented at the 52nd annual American Association for the Study of Liver Disease (AASLD) conference in Dallas on November 11, 2001.

``Omega interferon is a natural human interferon produced by genetic engineering technologies,'' said BioMedicines' Chief Medical Officer, Dr. Peter Langecker. ``Results from these two independent studies provide evidence for an antiviral effect against all HCV genotypes (1, 2, 3, and 4). Despite occasional symptoms typically associated with interferon treatment, patients appeared to tolerate omega interferon quite well. As a result, we were able to continue raising the dose level, producing progressive anti-hepatitis C effects.''

The European study was undertaken to evaluate the safety, tolerability and antiviral activity of six different dose levels of omega interferon in previously untreated patients with chronic hepatitis C. In this open-label study patients were treated for 3-12 months. All major HCV genotypes were present. Antiviral activity was assessed by measuring blood levels of HCV RNA and by liver enzyme testing. The interim results show that omega interferon can reduce HCV to undetectable levels in interferon-naive patients having any of the four major HCV genotypes.

The U.S. study was designed to evaluate the effect of increasing dose levels of omega interferon in three groups of patients with genotype 1, hepatitis C infection that was completely resistant to prior treatment with alpha interferon given with or without a second antiviral drug. Resistance meant that HCV was always detectable in blood despite treatment with alpha interferon. Within 48 hours of the initiation of treatment with omega interferon, HCV RNA fell sharply in all patients, and in some to undetectable levels.

Chief Executive Officer Dr. Mark Moran said, ``We are pleased with these results. We believe they also support our new drug delivery efforts with this drug. In collaboration with ALZA, we are also putting omega interferon into the implantable DUROS® delivery system. With DUROS®, we hope to be able to deliver omega interferon for months with a single administration.''

Hepatitis C infection can lead to severe impairment of liver function, liver fibrosis, and liver cancer. According to the U.S. Center for Disease Control, HCV infects nearly 3 million people in the United States, and the World Health Organization estimates 170 million people are infected worldwide. Many infected persons are unaware of the infection. The spread of HCV infection has reached epidemic proportions, as some experts believe that without substantial improvements in treatment, the death toll from HCV infection will surpass that from HIV.

About BioMedicines, Inc.

BioMedicines, Inc., a privately held pharmaceutical company, is developing first line therapies for the treatment of cancer and infectious diseases such as viral hepatitis. The company specializes in redirecting the development of drugs to new and more valuable indications. The company has current development and/or commercialization agreements with ALZA Corporation, Boehringer Ingelheim International GmbH, Schering AG, and G.D. Searle & Co. Additional information about BioMedicines, Inc. can be found on the World Wide Web at http://www.biomedicinesinc.com.

99% OF PATIENTS REMAIN FREE OF HEPATITIS C VIRUS WHEN TESTED THREE YEARS LATER

Study on long-term efficacy of PEGASYSâ, peginterferon alfa-2a (40KD)presented at American Association for the Study of Liver Diseases (AASLD)

Mississauga, Ontario (November 12, 2001) - The first study evaluating the long-term effectiveness of PEGASYSâ, peginterferon alfa-2a (40KD), a promising new hepatitis C (HCV) treatment, has found that 99% of patients remain viral free when examined two to three years later. Results of this study were presented today at the 52nd Annual Meeting of the American Association for the Study of Liver Diseases.

"Our study findings should give hepatitis C patients confidence that if they are virus free six months after completing therapy, they are very likely 'cured' of their disease," said Dr. Mark Swain, the principal investigator from the University of Calgary, Alberta, Canada.

Importantly, two-thirds of the HCV patients participating in this study were originally infected with genotype 1 HCV, which is associated with a lower overall response to therapy. Genotype 1 also represents the majority of those infected with hepatitis C in North America and Europe. Furthermore, 25 per cent of patients had cirrhosis of the liver, another difficult-to-treat population.

To date, more than 300 patients have enrolled in the study, which includes patients that had previously participated in one of the three Phase III studies. Patients were included if they had completed the 24-week follow-up period in the original study and patients could not be on any anti-HCV therapy subsequent to their original treatment. All patients were off original therapy for two to three years.

"Each year, 1,000 more Canadians are infected with this potentially fatal disease. Any drug or combination of drugs that can improve quality of life and health represents a major step forward for Canadian patients," said Tim McClemont, Executive Director of the Hepatitis C Society of Canada.

Hepatitis C: The Silent Epidemic
In Canada, chronic hepatitis C, recognized as a silent epidemic, is estimated to affect some 300,000 people. Of this total, only about one-third know they have the disease. Worldwide, more than 170 million people are infected and it is approximately four times more common than HIV. It is estimated that 20 per cent of people with hepatitis C develop cirrhosis of the liver, which can permanently injure and scar the liver. The scarred liver tissue interferes with the flow of blood through the liver, decreasing normal liver function, which can ultimately lead to liver cancer or death. Not only are patients with cirrhosis the hardest to treat, liver failure due to hepatitis C-related cirrhosis is the leading cause of liver transplants in Canada.

About PEGASYS
PEGASYS is a new, investigational, longer lasting form of interferon alfa-2a for the treatment of hepatitis C, developed by Roche. The PEG reagent used in pegylation, the process used to make PEGASYS, results in a unique branched structure that allows the interferon to remain active in the body attacking the virus for a longer period of time. PEGASYS has been submitted to Health Canada for approval and is currently under review.

About Roche
Roche is an international healthcare company committed to the discovery and development of new and innovative medicines to help treat human illnesses. Represented in more than 70 countries, the company is a world leader in the research and development of innovative pharmaceuticals, vitamins, fine chemicals and diagnostic equipment. The company is active in a broad range of therapeutic categories that include: AIDS, cardiology, dermatology, hepatitis C, infectious disease, metabolism, transplant, oncology and virology.

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

Three Rivers Counter-Sues Schering Corporation Over Ribavirin

Cranberry Township, Pennsylvania, November 21, 2001 - Three Rivers Pharmaceuticals, LLC, a startup generic drug manufacturer, today sued Schering Corporation in United States Federal District Court for the Western District of Pennsylvania. Three Rivers asserts that Schering has engaged in unfair competition under Pennsylvania law. Three Rivers also seeks a declaration that its generic version of ribavirin does not infringe Schering's patents, and that Schering's patents are invalid. Three Rivers has asserted these causes of action as counterclaims in an infringement action initiated by Schering.

Ribavirin has been found to be an effective treatment for hepatitis C, when used in combination with interferon. At present, only Schering's brand of ribavirin has been approved by the FDA for commercial production and sale. Schering initiated litigation shortly after Three Rivers submitted an Abbreviated New Drug Application (ANDA) seeking approval from the FDA to manufacture and market a generic form of ribavirin manufactured using a substantially different process. Three Rivers plans to offer their ribavirin at a substantially lower price than charged by Schering for its form of ribavirin.

"Three Rivers intends vigorously to defend itself and to press its claims against Schering for unfair competition," said Company President, Donald Kerrish. "Three Rivers remains committed to providing a high quality, affordable generic version of ribavirin, within the financial reach of all those afflicted with hepatitis C."

THREE RIVERS PHARMACEUTICALS, LLC CRANBERRY COMMERCE CENTER, 312 COMMERCE PARK DRIVE, CRANBERRY TOWNSHIP, PA 16066
PHONE: (724) 778-6100     FAX: (724) 778-6101

RICHMOND, Va., Nov. 13 /PRNewswire/ -- Patients being treated for the hepatitis C virus -- a blood-borne disease that attacks the liver -- now can learn earlier than ever before if they are likely to benefit from an investigational drug therapy. The findings are based on analysis of data from a Phase-3 study of pegylated interferon alfa-2a (Pegasys), a longer acting form of the medication interferon. The report was presented today (Nov.12) in Dallas, TX at the annual meeting of the American Association for the Study of Liver Disease.

According to the data, how patients respond after 12 weeks of treatment to pegylated interferon alfa-2a, combined with the anti-viral drug ribavirin, is a good indicator of how likely they are to respond to the medication long- term. Until now physicians had to wait six months before they could determine initial treatment results.

64 percent of patients who showed a marked decrease in the presence of the hepatitis C virus at week 12 were more likely to have a long-term sustained virologic response. At the same time, 98 percent of patients who had little or no response to treatment by the 12th week failed to exhibit a SVR at the conclusion of treatment. The data also shows patients who achieve a SVR rarely experience a recurrence of the hepatitis C virus.

``Being able to determine early on whether a treatment is going to effective ultimately will enable physicians to provide a better quality of care to their patients,'' said Mitchell Shiffman, M.D., chief of hepatology and professor of medicine at Virginia Commonwealth University's Medical College of Virginia Hospitals.

Treatment for hepatitis C generally involves a year-long regimen of interferon -- the only known medication for treating the virus. But because the side effects from the drug can be severe, including flu-like symptoms, depression, dizziness and nausea, patients are often reluctant to commit to taking the drug for such a long period of time.

``Committing to one year of therapy is difficult for many patients,'' said Shiffman. ``When patients hear the initial phase of treatment is now only three months long, and then we evaluate how they are doing, it becomes a more reasonable time frame for them. If the drug is working, we continue with it. If not, we stop and look for other options.'' The potency of pegylated interferon alfa-2a is the primary factor in being able to determine the drug's early effectiveness, according to Shiffman. "Its ability to drive down the levels of the virus in some patients so quickly after initiating treatment has enabled us to better predict the drugs long- term effectiveness."

Standard interferon therapy must be administered by injection three times a week and leaves the body in six hours. Pegylated interferon is injected only once a week and remains in the body for up to a week because the body absorbs it more slowly. The long-acting properties of pegylated interferon alfa-2a result in constant viral suppression, while at the same time, stimulate the immune system to attack it.

Chronic hepatitis C affects an estimated 3 million Americans and is the most common cause of liver disease. Left untreated, the virus can lead to cirrhosis, liver cancer and, in some cases, necessitate a liver transplant.

VCU is one of about 40 sites worldwide studying pegylated interferon alfa- 2a. The drug, manufactured by Hoffmann-La Roche Inc., is awaiting approval from the U.S. Food and Drug Administration.

SOURCE: Virginia Commonwealth University

ICN Presents New Data on Viramidine(TM) and Levovirin(TM) At The AASLD Annual Meeting

DALLAS, Nov. 12 /PRNewswire/ -- New pre-clinical research on Viramidine(TM), a potential prodrug of ribavirin for chronic hepatitis C, suggests that it might be more effective with fewer side effects than ribavirin. Ribavirin (Rebetol capsules) is now part of the combination therapy that represents the most effective treatment currently available for this infection. The data were presented today at the American Association for the Study of Liver Diseases (AASLD) Annual Meeting in Dallas.

New data on Levovirin(TM), a L-isomer of ribavirin, which has been shown to have similar immunomodulatory activity as ribavirin but with a much safer profile, were also presented at this meeting.

In an oral presentation entitled "Immunomodulatory Activities of Viramidine, a Liver-Targeting Ribavirin Prodrug, in vitro and in vivo," Johnson Yiu-Nam Lau, M.D., Senior Vice President of ICN Pharmaceuticals and co-author of the study, stated that results of the study indicate that Viramidine has a more favorable tissue distribution profile than ribavirin. Because Viramidine targets the liver better than ribavirin, the study's findings demonstrate that Viramidine is potentially safer than ribavirin. Viramidine may represent a next-generation analog of ribavirin, as does Levovirin(TM), which has been licensed to Roche for development.

Another study, "Viramidine, A Prodrug of Ribavirin, Demonstrated Superior Liver-Targeting Properties and a Much Improved Toxicity Profile in Cynomolgus Monkey Studies," evaluated whether Viramidine is a liver-targeted prodrug of ribavirin with an improved toxicity profile compared to ribavirin.

Test Cynomolgus monkeys received a daily dose of radiolabeled Viramidine or ribavirin for 10 days. Plasma and red blood cell samples were collected on days one and 10, and analyzed for radioactivity. Liver samples were also collected at 24 hours after the last dose (day 11) and evaluated for radioactivity. In monkeys, Viramidine was shown to be preferentially absorbed by the liver while being absorbed at a significantly lower level by red blood cells. The toxicity of Viramidine was also evaluated in a separate 28-day toxicity study in monkeys receiving different levels of oral dosage, which revealed that Viramidine is safer than ribavirin in the same dose.

"The preliminary findings from this research demonstrate that Viramidine may be a safer treatment for hepatitis C compared to ribavirin," according to Dr. Lau. "We look forward to conducting additional research to confirm this data."

"Chronic hepatitis C affects about 170 million people worldwide. Because of the great need for newer therapies with better efficacy and safety profiles, there is a considerable amount of scientific energy and focus in this therapeutic area," said Robert Gish, M.D., Medical Director, Liver Transplantation, California Pacific Medical Center, and Associate Clinical Professor, University of California-San Francisco School of Medicine. "The preliminary findings on Viramidine show the potential of this compound as a next generation ribavirin successor."

Studies were also presented on another ribavirin-related compound, Levovirin, which is also being developed as a potential treatment for chronic hepatitis C. Levovirin is an L-sugar isomer of ribavirin. In preclinical studies (Tam, Lin, Lau, ICN Pharmaceuticals, Costa Mesa, California, presented in the AASLD Annual Meeting 2000), Levovirin demonstrated similar immunomodulatory activity as ribavirin but a better tolerability profile. Most importantly, the compound has not shown genotoxic effects in in vitro and in vivo studies and it does not cause hemolytic anemia which is the major dose limiting side effect of ribavirin. Phase I clinical trials were initiated in February 2001.

Roche is currently developing Pegasys, its pegylated version of interferon alpha-2a, for the treatment of hepatitis C.

About Ribavirin

The oral form of ribavirin, a synthetic nucleoside analog, is licensed by ICN to Schering-Plough worldwide for the treatment of hepatitis C, and sold by Schering under the brand name Rebetol(R).

In the United States, Rebetron(R) (ribavirin) capsule was first approved in June 1998 to use in combination with interferon alpha-2b (Intron(R) A) injection for the treatment of adult patients with chronic HCV infection who relapsed after previous interferon alpha monotherapy. This combination therapy was also approved in December 1998 for adult patients who have not received previous treatment and have clinically compensated liver disease.

Recently, Peg-intron(TM) injection, a pegylated, longer-acting form of Intron A, received approval from the Food and Drug Administration for use in combination with Rebetol (ribavirin) for the treatment of chronic hepatitis C in patients not previously treated with interferon alpha and who have compensated liver disease and are at least 18 years of age. The response rate for those treated with ribavirin and pegylated interferon is 54% compared with a response rate of 47% for those receiving ribavirin and non-pegylated interferon in the same study.

ICN is also presenting additional data on remodeling the current concept of calculating the extent of ribavirin absorption in this meeting. This information will provide better understanding of the pharmacokinetic profile of ribavirin.

About Hepatitis C

Chronic hepatitis C, transmitted primarily through infected blood, is a potentially life-threatening viral infection that can lead to liver inflammation, liver disease, cirrhosis or liver cancer in a proportion of patients. Approximately 170 million people worldwide are infected with the hepatitis C virus, making hepatitis C more common than the HIV virus. Chronic hepatitis C is the leading cause of liver transplantation today.

About the AASLD Annual Meeting

The AASLD Annual Meetings define the leading edge in the study and treatment of liver and biliary diseases, presenting groundbreaking research and new clinical treatments. This year's Liver Meeting, held in Dallas, Texas, from November 9 to 13, has brought together more than 4,000 researchers from 55 countries. Over half of the attendees are from outside of the USA.

About ICN

ICN, headquartered in Costa Mesa, California, is an innovative research- focused global pharmaceutical company that manufactures, markets and distributes a broad range of prescription and non-prescription pharmaceuticals under the ICN brand name. Its therapeutic focus is in anti-infectives, including anti-virals, dermatology and oncology. Ribavirin, Levovirin, and Viramidine were discovered in ICN laboratories.

The Safe Harbor Statement Under The Private Securities Litigation Reform Act Of 1995. This press release contains forward-looking statements that involve risks and uncertainties, including but not limited to, projections of future sales, operating income, returns on invested assets, regulatory approval processes and other risks detailed from time to time in the company's Securities and Exchange Commission filings.

SOURCE ICN Pharmaceuticals