Phase 3 Trials of Albuferon

Human Genome Sciences Announces Positive Results in Second of Two Phase 3 Trials of Albuferon(R) in Chronic Hepatitis C
ROCKVILLE, MD UNITED STATES
- 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 -- Human Genome Sciences, Inc. (Nasdaq: HGSI) today announced that Albuferon(R) (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.
"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.
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.
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.
Conference Call
HGS management will hold a conference call to discuss this announcement today at 8:15 AM Eastern. Investors may listen to the call by dialing 888-203-1112 or 719-457-0820, passcode 4076361, five to 10 minutes before the start of the call. A replay of the conference call will be available within a few hours after the call ends. Investors may listen to the replay by dialing 888-203-1112 or 719-457-0820, confirmation code 4076361. A replay of the conference call will be available within a few hours after the call ends. Investors may listen to the replay by dialing (888) 203-1112 or (719) 457-0820 confirmation code 4076361. Today's conference call also will be webcast and can be accessed at www.hgsi.com. Investors interested in listening to the live webcast should log on before the conference call begins to download any software required. Both the audio replay and the archive of the conference call webcast will remain available for several days.
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. 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 ABthrax(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 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.
For more information about HGS, please visit the Company's web site at www.hgsi.com. Health professionals and patients interested in clinical trials of HGS products may inquire via e-mail to clinical_trials@hgsi.com or by calling HGS at (301) 610-5790, extension 3550.
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.
SOURCE Human Genome Sciences, Inc.