Human Genome Sciences Announces Albuferon(R) Meets Primary Endpoint In Phase 3 Trial In Chronic Hepatitis C 09 Dec 2008

Human Genome Sciences, Inc. (Nasdaq: HGSI) announced that Albuferon(R) (albinterferon alfa-2b) met its primary endpoint of non-inferiority to peginterferon alfa-2a (Pegasys) in ACHIEVE 2/3, a Phase 3 clinical trial of Albuferon in combination with ribavirin in treatment-naive patients with genotypes 2 and 3 chronic hepatitis C (p=0.0086). Albinterferon alfa-2b is being developed by HGS and Novartis under an exclusive worldwide co-development and commercialization agreement entered into in June 2006.

"We are pleased that Albuferon met its primary endpoint in the ACHIEVE 2/3 trial. These Phase 3 data show that the efficacy of Albuferon was comparable to Pegasys, with half the injections," said H. Thomas Watkins, President and Chief Executive Officer, HGS. "We look forward to having the results of ACHIEVE 1, our other Phase 3 trial of Albuferon, in March 2009. If ACHIEVE 1 is successful, we believe Albuferon could become the market-leading interferon for the treatment of chronic hepatitis C, and we expect that global marketing applications will be filed by fall 2009."

David Nelson, M.D., Professor of Medicine, Medical Director of Liver Transplantation, and Chief of the Hepatobiliary Disease Section, University of Florida, said, "Chronic hepatitis C represents a significant unmet medical need. These Phase 3 results suggest that albinterferon alfa-2b has the potential to become an important new treatment option for patients with chronic hepatitis C. Albuferon requires half as many injections as the pegylated interferons, and clinical results to date suggest that it may offer comparable efficacy, with no difference in clinically significant adverse events. The observed variation in response by geography is an unexpected finding and requires further analysis. We look forward to results from the ACHIEVE 1 trial, which is evaluating albinterferon alfa-2b in the treatment of patients with genotype 1 hepatitis C."

In the randomized, multi-center, active-controlled non-inferiority Phase 3 trial, 933 treatment-naive patients with genotypes 2 and 3 chronic hepatitis C were initially assigned to one of three treatment groups, including two groups that received albinterferon alfa-2b once every two weeks at doses of 900-mcg or 1200-mcg, and an active control group that received peginterferon alfa-2a once weekly at a dose of 180-mcg - with all patients receiving oral ribavirin daily at 800-mg in two divided doses. In January 2008, a dose modification was made and patients originally assigned to receive the 1200-mcg dose of albinterferon alfa-2b had their dose reduced to 900-mcg albinterferon alfa-2b every two weeks. The dose modification was recommended by the independent Data Monitoring Committee (DMC) for the Albuferon Phase 3 trials, following their observation during a routine review of unblinded data from both trials that serious pulmonary adverse events were higher in the 1200-mcg Albuferon treatment group. Following the dose modification, the study continued to follow all patients randomized into the trial on an intention-to-treat (ITT) basis according to their original dose assignment. The primary data analysis compares the 900-mcg albinterferon alfa-2b treatment group to the peginterferon alfa-2a treatment group. The trial included 24 weeks of treatment, and the primary efficacy endpoint was non-inferiority to peginterferon alfa-2a, based on a comparison of the rate of SVR, defined as undetectable viral load (HCV RNA < 10 IU/mL) at Week 48 (24 weeks following completion of treatment).

"We are encouraged that albinterferon alfa-2b met the primary efficacy endpoint of non-inferiority to peginterferon alfa-2a in the ACHIEVE 2/3 study," said David C. Stump, M.D., Executive Vice President, Research and Development, HGS. "These data show that the rate of sustained virologic response was comparable for the treatment group receiving the 900-mcg dose of albinterferon alfa-2b every two weeks, versus the treatment group receiving the standard dose of peginterferon alfa-2a once weekly. Importantly, the number of serious and severe adverse events, including pulmonary adverse events, was also comparable. When we have ACHIEVE 1 results in March, we will be in a position to assess the full therapeutic potential of albinterferon alfa-2b."

Key Findings from ACHIEVE 2/3

The topline ACHIEVE 2/3 results include the following key findings:

Treatment Group Receiving Albinterferon Alfa-2b 900-mcg Every Two Weeks, vs. Treatment Group Receiving Peginterferon Alfa-2a 180-mcg Every Week

-- Based on an ITT analysis of the treatment group assigned to receive 900-mcg albinterferon alfa-2b every two weeks, the topline results demonstrate that albinterferon alfa-2b met its primary efficacy endpoint of non-inferiority to peginterferon alfa-2a, with 79.8% (249/312) of patients achieving SVR in the 900-mcg albinterferon alfa-2b treatment group, vs. 84.8% (263/310) in the peginterferon alfa-2a treatment group (p=0.0086 for non-inferiority).

-- By region, SVR rates were

-- North America: 82.5% (85/103) for 900-mcg albinterferon alfa-2b, vs. 81.5% (88/108) for peginterferon alfa-2a;

-- Asia: 79.8% (75/94) for 900-mcg albinterferon alfa-2b, vs. 95.5% (85/89) for peginterferon alfa-2a;

-- Europe: 78.1% (64/82) for 900-mcg albinterferon alfa-2b, vs. 81.7% (67/82) for peginterferon alfa-2a;

-- Other regions: 75.8% (25/33) for 900-mcg albinterferon alfa-2b, vs. 74.2% (23/31) for peginterferon alfa-2a.

-- Patients receiving 900-mcg albinterferon alfa-2b had comparable rates of serious adverse events, severe adverse events, and discontinuations due to adverse events, vs. peginterferon alfa-2a.

-- The incidence of severe and/or serious adverse events was comparable between the two groups, with 17.3% (54/313) in the albinterferon alfa-2b 900-mcg treatment group, vs. 17.5% (54/309) in the peginterferon alfa-2a treatment group.

-- The incidence of severe and/or serious pulmonary adverse events was also comparable between these groups: severe and/or serious pulmonary infections were 0.6% (2/313) for 900-mcg albinterferon alfa-2b, vs. 0.6% (2/309) for peginterferon alfa-2a; and severe and/or serious respiratory, thoracic or mediastinal disorders were 1.0% (3/313) for 900-mcg albinterferon alfa-2b, vs. 1.3% (4/309) for peginterferon alfa-2a.

-- Overall, adverse events observed were those typically associated with interferon therapy, and the rate of discontinuations due to adverse events was comparable: 4.8% (15/313) for 900-mcg albinterferon alfa-2b, vs. 3.6% (11/309) for peginterferon alfa-2a.

Treatment Group Originally Randomized to Receive Albinterferon Alfa-2b 1200-mcg Every Two Weeks and Reduced to 900-mcg Following January 2008 Dose Modification, vs. Treatment Group Receiving Peginterferon Alfa-2a 180-mcg Every Week

Due to the dose modification announced in January 2008, patients in the treatment group originally randomized to receive albinterferon alfa-2b 1200-mcg every two weeks had their dose modified to 900-mcg albinterferon alfa-2b every two weeks. All patients had completed at least 12 weeks of treatment at the time of the dose modification. Data from all three treatment groups in the ACHIEVE 2/3 study were analyzed according to the original dose assignment. The following topline results for the treatment group originally randomized to receive 1200-mcg albinterferon alfa-2b every two weeks did not impact the primary analysis comparing the 900-mcg albinterferon alfa-2b treatment group to the peginterferon alfa-2a treatment group.

-- Based on an ITT analysis of results for the treatment group originally randomized to receive 1200-mcg albinterferon alfa-2b every two weeks, 80.0% (248/310) of patients in this treatment group achieved SVR, vs. 84.8% (263/310) in the peginterferon alfa-2a treatment group, which statistically demonstrated non-inferiority (p=0.0059).

-- The incidence of severe and/or serious adverse events was comparable between the two groups, with 16.8% (52/310) in the treatment group originally randomized to receive 1200-mcg albinterferon alfa-2b every two weeks, vs. 17.5% (54/309) in the peginterferon alfa-2a treatment group.

-- The incidence of severe and/or serious pulmonary adverse events was also comparable between these groups: severe and/or serious pulmonary infections were 1.3% (4/310) in the treatment group originally randomized to receive 1200-mcg albinterferon alfa-2b, vs. 0.6% (2/309) in the peginterferon alfa-2a treatment group; severe and/or serious respiratory, thoracic or mediastinal disorders were 1.6% (5/310) in the treatment group originally randomized to receive 1200-mcg albinterferon alfa-2b, vs. 1.3% (4/309) in the peginterferon alfa-2a treatment group.

-- Overall, adverse events observed were those typically expected with interferon therapy. The incidence of discontinuations due to adverse events was 5.5% (17/310) in the treatment group originally randomized to receive 1200-mcg albinterferon alfa-2b every two weeks, vs. 3.6% (11/309) in the peginterferon alfa-2a treatment group.