HUMAN GENOME SCIENCES AND GLAXOSMITHKLINE ANNOUNCE TOPLINE 76-WEEK RESULTS OF PHASE 3 TRIAL OF BENLYSTATM IN SYSTEMIC LUPUS ERYTHEMATOSUS
ROCKVILLE, Maryland, and LONDON, UK - April 20, 2010 - Human Genome Sciences, Inc. (Nasdaq: HGSI) and GlaxoSmithKline PLC (GSK) today announced topline secondary endpoints from BLISS-76, the second of two pivotal Phase 3 trials of BENLYSTATM (belimumab) in seropositive patients with systemic lupus erythematosus (SLE). BENLYSTA 10 mg/kg already met its primary efficacy endpoint at Week 52 in both BLISS-52 and BLISS-76, as announced in July and November 2009.
At Week 76 in the BLISS-76 study, belimumab plus standard of care showed higher response rates compared with placebo plus standard of care as measured by the SLE Responder Index; however, this secondary endpoint did not reach statistical significance. Study results also showed that belimumab continued to be generally well tolerated, as demonstrated by a similar rate of discontinuations due to adverse events across treatment groups, with overall adverse event rates comparable between belimumab and placebo treatment groups.
"A positive overall picture has emerged from our pivotal Phase 3 studies of BENLYSTA, including its achievement of statistical significance on the primary efficacy endpoint at Week 52 with a favorable safety profile in both BLISS-52 and BLISS-76," said H. Thomas Watkins, President and Chief Executive Officer, HGS. "We view the results of these studies as strongly supportive of our view that BENLYSTA has the potential to become the first new approved drug in more than 50 years for people living with systemic lupus."
Carlo Russo, M.D., Senior Vice President, Biopharm Development, GSK, said, "Based on the totality of data in BLISS-52 and BLISS-76, we believe that belimumab could deliver a significant therapeutic option for patients with lupus, a chronic condition which has a devastating effect on the lives of patients living with the disease."
The data from the BLISS-76 study were previously analyzed after 52 weeks in accord with the study protocol, in support of a potential Biologics License Application in the United States and Marketing Authorization Applications in Europe and other regions. The primary efficacy endpoints in both pivotal Phase 3 studies of belimumab, BLISS-52 and BLISS-76, were the patient response rates at Week 52 as measured by the SLE Responder Index. BLISS-76 then continued for an additional 24 weeks. Belimumab is an investigational drug and the first in a new class of drugs called BLyS-specific inhibitors. Belimumab is being developed by HGS and GSK under a co-development and commercialization agreement entered into in 2006.
Key Findings from BLISS-76
"These new data from BLISS-76 provide additional evidence of the beneficial effect of belimumab despite not reaching statistical significance on the secondary endpoint. The results of our Phase 3 trials support a potentially important role for belimumab added to standard of care for the treatment of seropositive patients with systemic lupus," said David C. Stump, M.D., Executive Vice President, Research and Development, HGS. "We and GSK are working together to complete and submit regulatory applications for belimumab in the United States and Europe in the second quarter of this year. We look forward to the full presentation of BLISS-76 52-week and 76-week results at appropriate scientific meetings later this year."
Based on an intention-to-treat (ITT) analysis, patient response rates for belimumab plus standard of care versus placebo plus standard of care, as measured by the SLE Responder Index (SRI) at Week 76, were: 38.5% for 10 mg/kg belimumab, 39.1% for 1 mg/kg belimumab, and 32.4% for placebo (p=0.13 and p=0.11 for 10 mg/kg and 1 mg/kg belimumab, respectively vs. placebo). The SRI defines patient response as an improvement in SELENA SLEDAI score of 4 points or greater, with no clinically significant BILAG worsening and no clinically significant worsening in Physician's Global Assessment.
Topline Week 76 results currently available for secondary endpoints include:
■The proportion of patients with a reduction in SELENA SLEDAI score of at least 4 points was 41.4% for belimumab 10 mg/kg, 42.1% for belimumab 1 mg/kg, and 33.8% for placebo (p=0.066 and p=0.049 for belimumab 10 mg/kg and 1 mg/kg, respectively vs. placebo).
■Mean improvement from baseline in Physician's Global Assessment (PGA) was 0.51 for belimumab 10 mg/kg, 0.53 for belimumab 1 mg/kg, and 0.49 for placebo (p=0.21 for both belimumab 10 mg/kg and for 1 mg/kg, vs. placebo).
■At entry into the BLISS-76 study, approximately 46% of patients were receiving steroids at a prednisone-equivalent dose of at least 7.5 mg per day. Among these patients, the percentage of patients who had their average steroid dose reduced by at least 25% from baseline to 7.5 mg per day or less during the last 12 weeks of the study (Week 64 through Week 76) was 24.2% for belimumab 10 mg/kg, 26.9% for belimumab 1 mg/kg, and 17.5%% for placebo (p=0.27 and p=0.07 for belimumab 10 mg/kg and 1 mg/kg, respectively, vs. placebo.
■In BLISS-76 at Week 76, the mean percent reduction in SELENA SLEDAI score was 37.0% for belimumab 10 mg/kg, 36.1% for belimumab 1 mg/kg, and 27.8% for placebo (p=0.01 and p=0.03 for 10mg/kg belimumab and 1 mg/kg belimumab, respectively vs. placebo). At Week 52, the reduction in SELENA SLEDAI was 36.0% for belimumab 10 mg/kg, 33.9% for belimumab 1 mg/kg, and 26% for the placebo (p<0.01 and p=0.04 for 10 mg/kg and 1 mg/kg belimumab, respectively vs. placebo).
■Biomarker responses have been studied throughout the program and belimumab consistently demonstrated a beneficial effect on anti double-stranded DNA and complement with both doses.
■Additional analyses are ongoing, including post-hoc analyses, to further understand these data.
In BLISS-76 through 76 weeks, belimumab was generally well tolerated, with rates of overall adverse events, serious and/or severe adverse events, all infections, serious and/or severe infections, and discontinuations due to adverse events comparable between treatment groups receiving belimumab plus standard of care and the treatment group receiving placebo plus standard of care. Serious and/or severe adverse events were reported in 29.0% of patients on belimumab and 26.2% of patients on placebo. Infections were reported in 74.3% of patients on belimumab and 69.1% of patients on placebo. Serious and/or severe infections were reported in 4.2% of patients on belimumab and 3.6% of patients on placebo. Serious and/or severe infusion reactions were reported in 1.1% of patients on belimumab and 0.7% of patients on placebo. Discontinuations due to adverse events were 7.5% in the belimumab treatment groups and 8.4% in the placebo treatment group. One new malignancy was reported since the Week 52 data were announced, with a total 2, 4, and 1 subjects in the belimumab 10 mg/kg, belimumab 1 mg/kg and placebo groups, respectively. No additional deaths were reported since the Week 52 data were announced, with a total of three deaths in the study: 1, 2, and 0 reported in the belimumab 10 mg/kg, belimumab 1 mg/kg and placebo groups, respectively.
About the Belimumab Phase 3 Development Program
The Phase 3 development program for belimumab included two double-blind, placebo-controlled, multi-center Phase 3 superiority trials - BLISS-52 and BLISS-76 - to evaluate the efficacy and safety of belimumab plus standard of care, versus placebo plus standard of care, in seropositive (HEp-2 ANA > 1:80 and/or anti-dsDNA > 30 IU/mL) patients with SLE. Both BLISS-52 and BLISS-76 have now been completed. This is the largest clinical trial program ever conducted in lupus patients. BLISS-52 randomized and treated 865 patients at 90 clinical sites in 13 countries, primarily in Asia, South America and Eastern Europe. BLISS-76 randomized and treated 819 patients at 136 clinical sites in 19 countries, primarily in North America and Europe. The design of the two trials was similar, but the duration of therapy in the two studies was different - 52 weeks for BLISS-52 and 76 weeks for BLISS-76. Data from BLISS-76 were analyzed after 52 weeks in support of a potential Biologics License Application in the United States and Marketing Authorization Applications in Europe and other regions. HGS designed the Phase 3 program for belimumab in collaboration with GSK and leading international SLE experts, and the program is being conducted under a Special Protocol Assessment agreement with FDA.
The primary efficacy endpoint of BLISS-52 and BLISS-76 was the patient response rate at Week 52 as measured by the SLE Responder Index, which is defined by: (1) a reduction from baseline of at least 4 points on the SELENA SLEDAI disease activity scale (which indicates a clinically important reduction in SLE disease activity); (2) no worsening of disease as measured by the Physician's Global Assessment (worsening defined as an increase of 0.30 points or more from baseline); (3) no new BILAG A organ domain score (which indicates a severe flare of lupus disease activity) and no more than one new BILAG B organ domain score (which indicates a moderate flare of disease activity). Analysis for the primary endpoint is based on intention-to-treat and adjusted for baseline stratification factors, including SELENA SLEDAI score, proteinuria and race. The patient response rate at Week 76 as measured by the SLE Responder Index was a protocol-specified major secondary endpoint of the BLISS-76 study.
In each of the two Phase 3 trials, patients were randomized to one of three treatment groups: 10 mg/kg belimumab (BLISS-52, n=290; BLISS-76, n=273), 1 mg/kg belimumab (BLISS-52, n=288; BLISS-76, n=271), or placebo (BLISS-52, n=287; BLISS-76, n=275). Patients were dosed intravenously on Days 0, 14 and 28, then every 28 days thereafter for the duration of the study. All patients received standard of care therapy in addition to the study medication. Safety was reviewed by an independent Data Monitoring Committee throughout both studies.
Belimumab is an investigational human monoclonal antibody drug that specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator, or BLyS. BLyS is a naturally occurring protein discovered by HGS that is required for the development of B-lymphocyte cells into mature plasma B cells. Plasma B cells produce antibodies, the body's first line of defense against infection. In lupus and certain other autoimmune diseases, elevated levels of BLyS are believed to contribute to the production of autoantibodies - antibodies that attack and destroy the body's own healthy tissues. The presence of autoantibodies appears to correlate with disease severity. Preclinical and clinical studies suggest that belimumab can reduce autoantibody levels in SLE. The results of two pivotal Phase 3 trials, BLISS-52 and BLISS-76, suggest that belimumab can reduce SLE disease activity.
About the HGS/GSK Collaboration
In 2006, HGS and GSK entered into a definitive co-development and commercialization agreement under which HGS is conducting the belimumab Phase 3 trials, with assistance from GSK. The companies will share equally in Phase 3/4 development costs, sales and marketing expenses, and profits of any product commercialized under the agreement.
About Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a chronic, life-threatening autoimmune disease. Approximately five million people worldwide, including approximately 1.5 million in the United States, suffer from various forms of lupus, including SLE. Lupus can occur at any age, but appears mostly in young people ages 15 to 45. About 90 percent of those diagnosed with lupus are women. African-American women are about three times more likely to develop lupus, and it is also more common in Hispanic, Asian and American Indian women. Symptoms may include extreme fatigue, painful and swollen joints, unexplained fever, skin rash and kidney problems. Lupus can lead to arthritis, kidney failure, heart and lung inflammation, central nervous system abnormalities, inflammation of the blood vessels and blood disorders. No new drug for lupus has been approved by regulatory authorities in more than 50 years. For more information on lupus, visit the Lupus Foundation of America at www.lupus.org, the Lupus Research Institute at www.lupusresearchinstitute.org, the National Institute of Arthritis and Musculoskeletal and Skin Diseases at www.niams.nih.gov, or Lupus Europe at www.elef.rheumanet.org.
HGS management will hold a conference call to discuss this announcement today at 8:00 AM Eastern. Investors may listen to the call by dialing 800-401-3551 or 913-981-5596, passcode 4047136, 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 4047136. 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.
GlaxoSmithKline's collaboration with HGS is led by its GSK Biopharm R&D division, which employs novel approaches to harness the therapeutic potential of biopharmaceuticals for the benefit of patients with serious autoimmune disease. This innovative research is one way GSK - one of the world's leading research-based pharmaceutical and healthcare companies - can deliver on its commitment to improve the quality of human life by enabling people to do more, feel better and live longer. For more information, visit GlaxoSmithKline on the World Wide Web at www.gsk.com.
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 lupus, hepatitis C, inhalation anthrax and cancer.
HGS, Human Genome Sciences and BENLYSTA are trademarks of Human Genome Sciences, Inc. Other trademarks referenced are the property of their respective owners.
HGS 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 Human Genome Sciences' unproven business model, its dependence on new technologies, the uncertainty and timing of clinical trials and regulatory approvals, Human Genome Sciences' 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, Human Genome Sciences' 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 SEC. 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.
GlaxoSmithKline Forward-Looking Statements
Under the safe harbor provisions of the US Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK's operations are described under 'Risk Factors' in the ‘Business Review' in GSK's Annual Report on Form 20-F for 2009.
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