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HCV
Albuferon in Phase 2b Trial for the Treatment of Chronic Hepatitis C
By Human Genome Sciences, Inc., Jun 2, 2005 - 1:15:38 PM

Human Genome Sciences, Inc. announced today that it has begun dosing patients in a Phase 2b clinical trial of Albuferon(TM) (albumin-interferon alpha) in combination with ribavirin to evaluate the efficacy and safety of Albuferon in patients with chronic hepatitis C virus (HCV) genotype 1 who are naive to interferon alpha-based treatment regimens. Genotype 1 accounts for nearly 70% of all HCV infections in North America and is generally regarded as the most difficult HCV genotype to treat.(1)

The trial is a randomized, open-label, multi-center, active-controlled, dose-ranging study conducted in Australia, Canada, Czech Republic, France, Germany, Israel, Poland and Romania. A minimum of 440 patients will be enrolled in the Phase 2b study and randomized into four treatment groups, three of which will receive subcutaneously administered Albuferon (900 mcg at 14-day intervals, 1200 mcg at 14-day intervals, and 1200 mcg at 28-day intervals(1)). The fourth treatment group will serve as the active control group and will receive weekly 180-mcg doses of subcutaneously administered Pegasys (peginterferon alfa-2a). All patients will receive weight-based oral daily ribavirin at 1000 or 1200 mg in two divided doses. The primary objectives of the Phase 2b study are to evaluate the efficacy and safety of Albuferon in combination with ribavirin in interferon alpha-naive patients with chronic hepatitis C genotype 1. The primary efficacy endpoint will be sustained virologic response, defined as undetectable virus at 24 weeks after completion of 48 weeks of treatment.

John McHutchison, M.D., Coordinating Center Principal Investigator for the Phase 2b study, and Professor of Medicine and Director, GI/Hepatology Research, Duke Clinical Research Institute and Duke University Medical Center, Durham, NC, said, "The current standard of care for the treatment of chronic hepatitis C is a combination of pegylated interferon alpha and ribavirin. This combination produces cures in approximately 42-46 percent of all genotype 1 HCV patients completing therapy, leaving more than 50 percent who relapse or do not respond. Clearly, chronic hepatitis C represents a significant unmet medical need. The preclinical and clinical evidence to date supports the continued evaluation of the potential of Albuferon to help meet this need. The next logical step is the current study of Albuferon in combination with ribavirin in a larger population of treatment-naïve genotype 1 patients with chronic hepatitis C."(2-11)

David C. Stump, M.D., Executive Vice President, Drug Development, said, "Based on the preclinical and clinical results that have emerged thus far, we believe that Albuferon has the potential to become an important therapeutic option for the treatment of chronic hepatitis C. The Phase 2b study announced today is the largest Albuferon trial to date. We recently reported the positive results of a Phase 2 study of Albuferon monotherapy in interferon alpha-naïve patients with genotype 1 hepatitis C.(12-13) The data that emerged demonstrate that Albuferon is well tolerated, has a prolonged half- life and shows robust antiviral activity, with durable dose-dependent reductions in HCV viral load. The data also enabled our identification of the range of active doses that will be evaluated in the larger Phase 2b trial announced today. In February 2005, we disclosed preliminary data from a separate ongoing Phase 2 clinical trial of Albuferon in combination with ribavirin, which show that Albuferon can be administered safely and repetitively at 2-week or 4-week intervals in combination with ribavirin in patients who have failed to respond to previous interferon alpha-based treatment regimens.(14) The results of clinical and preclinical studies to date afford confidence in the ability to administer Albuferon safely in combination with ribavirin to treatment-naïve patients.(15-21) We are hopeful that Albuferon will one day provide an important therapeutic option for the treatment of chronic hepatitis C."

The results of a Phase 2 clinical trial of Albuferon monotherapy in interferon alpha-naive patients with genotype 1 chronic hepatitis C were presented at the 40th Annual Meeting of the European Association for the Study of the Liver (EASL).(12-13)

Data presented on 56 patients demonstrate that Albuferon exhibited robust antiviral activity in genotype 1 HCV. A mean reduction in HCV viral load of 3.2 log at Day 28 was observed in the combined 900 mcg and 1200 mcg dose cohorts, with 69% of patients (18/26) in these cohorts showing a more than 2-log reduction in HCV viral load at Day 28. Undetectable viral load was observed at Day 42 (28 days after the second injection) in 23% of patients (6/26) in the combined 900 mcg and 1200 mcg dose cohorts.

Robust dose-dependent viral kinetics were observed, with the majority of patients in the 900 mcg and 1200 mcg cohorts exhibiting a second-phase decline in viral load of more than 0.3 log per week, which has previously been shown to be predictive of sustained virologic response (SVR) in treatment with the pegylated interferons.(22)

Reductions in viral load of equal to or greater than 2 log are reported in approximately 42% of genotype 1 HCV patients treated with pegylated interferon alpha products in combination with ribavirin.(23) The results presented at EASL demonstrate that Albuferon remained in the blood substantially longer than is reported for recombinant interferon alpha and pegylated interferon alpha. Albuferon exhibited a median half-life of 148 hours, supporting dosing at intervals of 2-4 weeks. This compares with a reported mean (range) elimination half-life of 80 hours (50-140 hours) for Pegasys and 40 hours (22-60 hours) for PEG-Intron.(23-25) Albuferon was well tolerated with adverse events that were transient and mostly mild to moderate in severity. There were no discontinuations due to reductions in hematologic cell counts. No subjects developed newly emergent antibodies to alpha interferon.

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.

Hepatitis C infection is an inflammation of the liver caused by the hepatitis C virus. It is the most common chronic blood-borne infection in the developed world. It is estimated that as many as 170 million people worldwide are infected with hepatitis C virus. This includes nearly four million people in the United States. The hepatitis C virus is transmitted primarily through significant or repeated exposures to infected blood. 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.

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