Human Genome Sciences Reports Positive Late-Breaker Results at EASL from ACHIEVE Phase 3 Trials of Albuferon(R) in Patients with Chronic Hepatitis C
- With half as many injections, in two pivotal Phase 3 trials, Albuferon (albinterferon alfa-2b) met the primary efficacy endpoint of sustained virologic response comparable to Pegasys (peginterferon alfa-2a) -
- Patients receiving 900-mcg Albuferon had comparable rates of serious and/or severe adverse events across the two Phase 3 trials, versus peginterferon alfa-2a -
- Submission of global marketing applications planned in fall 2009 -
ROCKVILLE, Md., April 25 /PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. (Nasdaq: HGSI) today reported that the final results of two pivotal Phase 3 trials demonstrate that Albuferon(R) (albinterferon alfa-2b) met its primary endpoint of non-inferiority to peginterferon alfa-2a (Pegasys) in the treatment of patients with chronic hepatitis C. The Phase 3 results were the subject of two late-breaker oral presentations today in Copenhagen at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL). Albinterferon alfa-2b is being developed by HGS and Novartis under an exclusive worldwide co-development and commercialization agreement entered into in June 2006.
"The Phase 3 data presented at EASL show that Albuferon, with half the injections, achieved a rate of sustained virologic response comparable to Pegasys," said David C. Stump, M.D., Executive Vice President, Research and Development, HGS. "Importantly, the rates of serious and/or severe adverse events were also comparable in these studies. We plan to file global marketing applications in fall 2009, following discussions with regulatory authorities - and we believe that Albuferon, assuming licensure, could become a leading treatment for chronic hepatitis C."
The Phase 3 studies, known as ACHIEVE 1 and ACHIEVE 2/3, evaluated albinterferon alfa-2b vs. peginterferon alfa-2a, in combination with ribavirin, for use in the treatment of interferon-naive patients with chronic hepatitis C. ACHIEVE 1 was conducted in patients infected with genotype 1 virus, and ACHIEVE 2/3 was conducted in patients with genotypes 2 and 3 virus. The two studies treated a combined total of 2255 treatment-naive patients.
"The results of two Phase 3 trials demonstrate that 900-mcg albinterferon alfa-2b administered every two weeks provides efficacy comparable to peginterferon alfa-2a administered weekly, with a positive safety profile," said David Nelson, M.D., Professor of Medicine, Medical Director of Liver Transplantation, and Chief of the Hepatobiliary Disease Section, University of Florida. Dr. Nelson presented the results from ACHIEVE 2/3.
Stefan Zeuzem, M.D., Professor of Medicine and Chief, Department of Medicine, J.W. Goethe University Hospital, Frankfurt, Germany, presented the ACHIEVE 1 results, and said, "The data presented at EASL suggest that albinterferon alfa-2b has the potential to become an important and novel treatment option for patients with chronic hepatitis C."
Phase 3 Efficacy Findings
Based on an intention-to-treat (ITT) analysis, the data presented at EASL demonstrate that albinterferon alfa-2b met its primary efficacy endpoint of non-inferiority to peginterferon alfa-2a in both ACHIEVE 1 and ACHIEVE 2/3:
- ACHIEVE 1: 48.2% (213/442) of patients in the 900-mcg albinterferon alfa-2b treatment group achieved sustained virologic response (SVR), vs. 51.0% (225/441) in the peginterferon alfa-2a treatment group. The primary analysis, which was 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).
- ACHIEVE 2/3: 79.8% (249/312) of patients achieved SVR in the 900-mcg albinterferon alfa-2b treatment group, vs. 84.8% (263/310) in the peginterferon alfa-2a group (p=0.0086 for non-inferiority). The primary analysis, which was adjusted for baseline stratification factors, showed a difference in SVR rates of -4.8% (95% CI -10.7%, 1.1%, p=0.0086 for non-inferiority).
- An unexpectedly high and still unexplained SVR rate for peginterferon alfa-2a in the Asian region fully accounted for the observed SVR difference between the two drugs in the ACHIEVE 2/3 study.
- In non-Asian regions, 79.8% (174/218) of patients achieved SVR in the 900-mcg albinterferon alfa-2b treatment group, vs. 80.5% (178/221) in the peginterferon alfa-2a group. In Asia, 79.8% (75/94) of patients achieved SVR in the 900-mcg albinterferon alfa-2b treatment group, vs. 95.5% (85/89) in the peginterferon alfa-2a group.
Phase 3 Safety Findings
Across the two albinterferon alfa-2b Phase 3 trials, rates of serious and/or severe adverse events were comparable in all dose groups, including 21.2% (160/755) for 900-mcg albinterferon alfa-2b, and 20.8% (156/750) for 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% (1/755) for 900-mcg albinterferon alfa-2b every two weeks, and 0.27% (2/750) for 180-mcg peginterferon alfa-2a.
Rates of discontinuation due to adverse events across the two studies were 8.1% (61/755) for 900-mcg albinterferon alfa-2b, vs. 3.9% (29/750) for peginterferon alfa-2a. The causes of discontinuation for both drugs were those typical for interferon-based therapy.
Overall, adverse events observed were those typically associated with interferon therapy, and most were similar for 900-mcg albinterferon alfa-2b and peginterferon alfa-2a.
About the Design of the ACHIEVE Trials
The albinterferon alfa-2b Phase 3 clinical development program included two randomized, multi-center, active-controlled non-inferiority Phase 3 trials -- ACHIEVE 1 and ACHIEVE 2/3. In ACHIEVE 1, 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 ACHIEVE 2/3, 933 treatment-naive patients with genotypes 2 and 3 chronic hepatitis C were initially assigned to one of three treatment groups receiving the same doses on the same schedule of administration used in the ACHIEVE 1 study.
In January 2008, a dose modification was made in both studies for patients originally assigned to receive the 1200-mcg dose of albinterferon alfa-2b. These patients had their dose reduced to 900-mcg albinterferon alfa-2b every two weeks. Following the dose modification, both ACHIEVE 1 and ACHIEVE 2/3 continued to follow all patients randomized on an intention-to-treat (ITT) basis according to their original dose assignment. The primary data analysis in both studies compared the 900-mcg albinterferon alfa-2b treatment group to the peginterferon alfa-2a treatment group. The ACHIEVE 1 trial included 48 weeks of treatment, and the ACHIEVE 2/3 trial included 24 weeks of treatment. The primary efficacy endpoint for both trials was sustained virologic response (SVR), defined as undetectable viral load (HCV RNA<10 iu>
About Albinterferon Alfa-2b (Albuferon)
Albinterferon alfa-2b is a genetic fusion of human albumin and interferon alfa created using the proprietary HGS albumin-fusion technology. Human albumin is the most prevalent naturally occurring blood protein in the human circulatory system, persisting in circulation in the body for approximately 19 days. Research has shown that genetic fusion of therapeutic proteins to human albumin decreases clearance and prolongs the half-life of the therapeutic proteins.
Albuferon is being developed by HGS and Novartis for the treatment of chronic hepatitis C under an exclusive worldwide co-development and commercialization agreement entered into in June 2006. HGS and Novartis will co-commercialize Albuferon in the United States and will share clinical development costs, U.S. commercialization costs and U.S. profits equally. Novartis will be responsible for commercialization in the rest of the world and will pay HGS a royalty on those sales. Clinical development, commercial milestone and other payments to HGS could total as much as $507.5 million, including $132.5 million received to date.
Albuferon dosed once every two weeks has completed Phase 3 development. Global marketing applications are planned in fall 2009. In addition, Novartis has initiated a Phase 2b trial to evaluate Albuferon dosed once every four weeks.
About Hepatitis C
Hepatitis C is an inflammation of the liver caused by the hepatitis C virus. 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. When detectable levels of HCV persist in the blood for at least six months, a person is diagnosed with chronic hepatitis C. Hepatitis C virus can cause serious liver disease, leading to cirrhosis, primary liver cancer and even death. Patients infected with the genotype 1 hepatitis C virus account for approximately 75% of the chronic hepatitis C patients in the U.S.
About Human Genome Sciences
The mission of HGS is to apply great science and great medicine to bring innovative drugs to patients with unmet medical needs. The HGS clinical development pipeline includes novel drugs to treat hepatitis C, lupus, inhalation anthrax and cancer.
The Company's primary focus is rapid progress toward the commercialization of its two lead drugs, Albuferon(R) (albinterferon alfa-2b) for hepatitis C and LymphoStat-B(R) (belimumab) for lupus. The filing of global marketing applications for Albuferon is planned in fall 2009. Two Phase 3 clinical trials of LymphoStat-B are ongoing, with results expected in July and November 2009.
In January 2009, HGS began delivery of 20,000 doses of ABthrax(TM) (raxibacumab) to the U.S. Strategic National Stockpile for use in the event of an emergency for the treatment of inhalation anthrax; completion of delivery is expected in the second quarter. The Company also has several drugs in earlier stages of clinical development for the treatment of cancer, led by the TRAIL receptor antibody HGS-ETR1 and a small-molecule antagonist of IAP (inhibitor of apoptosis) proteins. In addition, HGS has substantial financial rights to certain products in the GSK clinical pipeline including darapladib, currently in Phase 3 development as a potential treatment for coronary heart disease, and Syncria(R) (albiglutide), currently in Phase 3 development as a potential treatment for type 2 diabetes.
HGS, Human Genome Sciences, ABthrax, Albuferon and LymphoStat-B are trademarks of Human Genome Sciences, Inc.
Safe Harbor Statement
This announcement contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The forward-looking statements are based on Human Genome Sciences' current intent, belief and expectations. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are difficult to predict. Actual results may differ materially from these forward-looking statements because of the Company's unproven business model, its dependence on new technologies, the uncertainty and timing of clinical trials, the Company's ability to develop and commercialize products, its dependence on collaborators for services and revenue, its substantial indebtedness and lease obligations, its changing requirements and costs associated with facilities, intense competition, the uncertainty of patent and intellectual property protection, the Company's dependence on key management and key suppliers, the uncertainty of regulation of products, the impact of future alliances or transactions and other risks described in the Company's filings with the Securities and Exchange Commission. In addition, while the Company has begun shipment of ABthrax to the U.S. Strategic National Stockpile, the Company will continue to face risks related to acceptance of future shipments and FDA's approval of the Company's Biologics License Application for ABthrax, if and when it is submitted. If the Company is unable to meet requirements associated with the ABthrax contract, future revenues from the sale of ABthrax to the U.S. Government will not occur. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today's date. Human Genome Sciences undertakes no obligation to update or revise the information contained in this announcement whether as a result of new information, future events or circumstances or otherwise.
Posted: April 2009