Human Genome Sciences Announces Positive Results in Second of Two Phase 3 Trials of Albuferon in Chronic Hepatitis C
ROCKVILLE, Md., March 09, 2009 /PRNewswire-FirstCall/ -- <!-- cpurl -->Human Genome Sciences<!-- /cpurl -->, Inc. today announced that <!-- ppurl -->Albuferon<!-- /ppurl -->(R) (albinterferon alfa-2b) met its primary endpoint of non-inferiority to peginterferon alfa-2a (<!-- ppurl -->Pegasys<!-- /ppurl -->) 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 <!-- cpurl -->Novartis<!-- /cpurl --> under an exclusive worldwide co-development and commercialization agreement entered into in June 2006.
"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. 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."
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.
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.
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.
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>
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.
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.
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 <!-- ppurl -->LymphoStat-B<!-- /ppurl -->(R) (belimumab) for lupus. Albuferon has now completed Phase 3 development, and the filing of global marketing applications is expected 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 <!-- ppurl -->ABthrax(<!-- /ppurl -->TM) (raxibacumab) to the U.S. Strategic National Stockpile for use in the event of an emergency for the treatment of inhalation anthrax. 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 <!-- ppurl -->darapladib<!-- /ppurl -->, currently in Phase 3 development as a potential treatment for coronary heart disease, and <!-- ppurl -->Syncria<!-- /ppurl -->(R) (albiglutide), currently in Phase 3 development as a potential treatment for type 2 diabetes.
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: March 2009