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Human Genome Sciences Announces Positive Results in Second of Two Phase 3 Trials of Albuferon(R) in Chronic Hepatitis C

Monday March 9, 7:00 am ET


- 900-mcg Albuferon (albinterferon alfa-2b) dosed every two weeks met the primary efficacy endpoint of sustained virologic response comparable to peginterferon alfa-2a dosed weekly in patients with genotype 1 chronic hepatitis C -


- Patients receiving 900-mcg Albuferon had comparable rates of serious and/or severe adverse events versus peginterferon alfa-2a -

- Filing of global marketing applications planned in fall 2009 -

ROCKVILLE, Md., March 9 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. (Nasdaq: HGSI - News) today announced that Albuferon® (albinterferon alfa-2b) met its primary endpoint of non-inferiority to peginterferon alfa-2a (Pegasys) in ACHIEVE 1, a Phase 3 clinical trial of Albuferon in combination with ribavirin in treatment-naive patients with genotype 1 chronic hepatitis C (p=0.0008). Albinterferon alfa-2b is being developed by HGS and Novartis under an exclusive worldwide co-development and commercialization agreement entered into in June 2006.

(Logo: http://www.newscom.com/cgi-bin/prnh/20080416/HGSLOGO )

"These Phase 3 data show that, with half the injections, the efficacy of Albuferon was comparable to Pegasys," said H. Thomas Watkins, President and Chief Executive Officer, HGS. "We are pleased that Albuferon met its primary endpoint in the ACHIEVE 1 trial as it also did in ACHIEVE 2/3. We look forward to the filing of global marketing applications in fall 2009, following discussions with regulatory authorities. Assuming licensure, we believe Albuferon could become a market-leading treatment for chronic hepatitis C."

Stefan Zeuzem, M.D., Professor of Medicine and Chief, Department of Medicine, J.W. Goethe University Hospital, Frankfurt, Germany, said, "These Phase 3 results in patients infected with the genotype 1 virus, evaluated together with the previously reported Phase 3 results in patients infected with the genotypes 2 and 3 viruses, suggest that albinterferon alfa-2b has the potential to become an important new treatment option for chronic hepatitis C."

"We are encouraged that albinterferon alfa-2b met the primary efficacy endpoint of non-inferiority to peginterferon alfa-2a in both of our pivotal Phase 3 studies," said David C. Stump, M.D., Executive Vice President, Research and Development, HGS. "As we found with the earlier results from ACHIEVE 2/3, the ACHIEVE 1 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 rate of serious and/or severe adverse events was also comparable for these treatment groups. We were pleased to see that serious pulmonary adverse events in the 900-mcg group were infrequent and all resolved with cessation of treatment."

Key Topline Findings from ACHIEVE 1

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 48.2% (213/442) of patients achieving SVR in the 900-mcg albinterferon alfa-2b treatment group, vs. 51.0% (225/441) in the peginterferon alfa-2a treatment group. The primary analysis, which is adjusted for baseline stratification factors, showed a difference in SVR rates of -1.8% (95% CI -8.1%, 4.5%, p=0.0008 for non-inferiority).
Patients receiving 900-mcg albinterferon alfa-2b had comparable rates of serious and/or severe adverse events, vs. peginterferon alfa-2a, with 24.0% (106/442) in the albinterferon alfa-2b 900-mcg treatment group, vs. 23.1% (102/441) in the peginterferon alfa-2a treatment group.
Serious and/or severe pulmonary adverse events were infrequent and included the following: The rate of serious and/or severe pulmonary infections was comparable between the two groups, with 1.8% (8/442) for 900-mcg albinterferon alfa-2b, vs. 1.1% (5/441) for peginterferon alfa-2a; the rate of serious and/or severe respiratory, thoracic or mediastinal disorders was 2.5% (11/442) for 900-mcg albinterferon alfa-2b, vs. 0.5% (2/441) for peginterferon alfa-2a. Of the 11 disorders reported for 900-mcg albinterferon alfa-2b, three were classified as serious, and all three resolved off treatment.
Overall, adverse events observed were those typically associated with interferon therapy. The rate of discontinuations due to adverse events was 10.4% (46/442) for 900-mcg albinterferon alfa-2b, vs. 4.1% (18/441) 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. Data from all three treatment groups in the ACHIEVE 1 study were analyzed according to the original dose assignment. The following 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, 47.3% (208/440) of patients in this treatment group achieved SVR, vs. 51.0% (225/441) in the peginterferon alfa-2a treatment group, which statistically demonstrated non-inferiority (95% CI -9.4%, 3.2%, p=0.0029, adjusted for baseline stratification factors).
The incidence of serious and/or severe adverse events was 28.3% (124/440) in the treatment group originally randomized to receive 1200-mcg albinterferon alfa-2b every two weeks, vs. 23.1% (102/441) in the peginterferon alfa-2a treatment group.
The incidence of serious and/or severe pulmonary adverse events included the following: serious and/or severe pulmonary infections were 3.2% (14/440) for 1200-mcg albinterferon alfa-2b, vs. 1.1% (5/441) for peginterferon alfa-2a; and serious and/or severe respiratory, thoracic or mediastinal disorders were 3.0% (13/440) for 1200-mcg albinterferon alfa-2b, vs. 0.5% (2/441) for peginterferon alfa-2a.
Overall, adverse events observed were those typically expected with interferon therapy. The incidence of discontinuations due to adverse events was 10.0% (44/440) in the treatment group originally randomized to receive 1200-mcg albinterferon alfa-2b every two weeks, vs. 4.1% (18/441) in the peginterferon alfa-2a treatment group.
Additional Safety Data of Interest from the Phase 3 Clinical Trials of Albinterferon Alfa-2b Versus Peginterferon Alfa-2a

HGS has conducted two randomized active-controlled Phase 3 clinical trials of albinterferon alfa-2b versus peginterferon alfa-2a - ACHIEVE 1 in genotype 1 chronic hepatitis C, and ACHIEVE 2/3 in genotypes 2 and 3 chronic hepatitis C. Overall, the two studies enrolled and randomized a total of 2264 treatment-naive patients.

The dose modification in January 2008 was recommended by the independent Data Monitoring Committee (DMC) based upon an interim analysis that serious pulmonary adverse events appeared to be higher in the 1200-mcg albinterferon alfa-2b treatment group.


Across the two Phase 3 trials, which have now been completed, rates of serious respiratory, thoracic or mediastinal disorders were: 0.7% (5/755) for 900-mcg albinterferon alfa-2b; 1.5% (11/750) for the group originally randomized to receive 1200-mcg albinterferon alfa-2b, and 0.0% (0/750) for peginterferon alfa-2a.
Central blinded review of chest X-rays recommended by the DMC for patients participating in the two Phase 3 trials demonstrated that the overall rates of significant interstitial findings were comparable in all three treatment groups: 4.3% (20/469) in patients randomized to receive 900-mcg albinterferon alfa-2b; 4.8% (22/454) in patients originally randomized to receive 1200-mcg albinterferon alfa-2b; and 4.5% (22/484) in patients randomized to receive 180-mcg peginterferon alfa-2a.
The incidence of fatality in the albinterferon alfa-2b Phase 3 trials was rare. All-cause mortality rates were: 0.13% (1/756) in patients randomized to receive 900-mcg albinterferon alfa-2b every two weeks; 0.53% (4/751) in patients originally randomized to receive 1200-mcg albinterferon alfa-2b every two weeks; and 0.27% (2/751) in patients randomized to receive 180-mcg peginterferon alfa-2a once-weekly.

Across the two Phase 3 trials, the overall percentage of patients who had a serious and/or severe adverse event or discontinued due to an adverse event was comparable in all dose groups: 23.2% (175/755) in patients randomized to receive 900-mcg albinterferon alfa-2b; 26.0% (195/750) in patients randomized to receive 1200-mcg albinterferon alfa-2b; and 21.6% (162/750) in patients randomized to receive 180-mcg peginterferon alfa-2a.

About the Design of the ACHIEVE 1 Trial

In the randomized, multi-center, active-controlled non-inferiority ACHIEVE 1 Phase 3 trial, 1331 treatment-naive patients with genotype 1 chronic hepatitis C were initially assigned to one of three treatment groups, including two groups that received subcutaneously administered 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 daily oral ribavirin concomitantly. In January 2008, a dose modification was made for patients originally assigned to receive the 1200-mcg dose of albinterferon alfa-2b. These patients had their dose modified to 900-mcg albinterferon alfa-2b every two weeks. 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 48 weeks of treatment, and the primary efficacy endpoint was sustained virologic response (SVR), defined as undetectable viral load (HCV RNA<10 IU/mL) at Week 72 (24 weeks following completion of treatment). A total of 2,264 patients with chronic hepatitis C have participated in the two Phase 3 trials of albinterferon alfa-2b.