Human Genome Sciences and GlaxoSmithKline Announce Full Presentation at EULAR of BLISS-76 Phase 3 Study Results for Benslyta in Systemic Lupus Erythematosus

ROCKVILLE, Md. & LONDON--(BUSINESS WIRE)--Jun 17, 2010 - Human Genome Sciences, Inc. (Nasdaq: HGSI) and GlaxoSmithKline PLC (GSK) today announced the full presentation of results from BLISS-76, one of two pivotal Phase 3 trials of BENLYSTA® (belimumab) in seropositive patients with systemic lupus erythematosus (SLE). The results will be presented today in Rome at the 2010 Congress of the European League Against Rheumatism (EULAR).

“The BLISS-76 Phase 3 results presented at EULAR extend the findings of previous studies and reinforce our belief that belimumab, assuming regulatory approval, could deliver a significant therapeutic option for seropositive patients with systemic lupus,” said David C. Stump, M.D., Executive Vice President, Research and Development, HGS. “In both of its pivotal Phase 3 trials in these patients, belimumab 10 mg/kg met its primary endpoint. The efficacy of treatment with belimumab plus standard of care compared with placebo plus standard of care was superior in both studies, with overall adverse event rates for belimumab comparable to placebo.”

Carlo Russo, M.D., Senior Vice President, Biopharm Development, GSK, said, “Belimumab is the first medicine developed specifically for lupus that has reached this late stage of clinical development with positive results. The BLISS-76 results presented at EULAR, taken together with the results of BLISS-52, reinforce our belief that belimumab may play an important role for patients living with lupus.”

Belimumab is an investigational drug and the first in a new class of drugs called BLyS-specific inhibitors. It is being developed by HGS and GSK under a co-development and commercialization agreement entered into in 2006. GSK submitted a Marketing Authorization Application to the European Medicines Agency (EMA) on June 4, 2010, seeking approval to market belimumab in Europe for treatment of autoantibody-positive patients with SLE. On June 10, 2010, HGS announced submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration seeking approval to market belimumab in the United States. No new drug for lupus has been approved by regulatory authorities in more than 50 years.

BLISS-76 PATIENT RESPONSE RATES (SRI)

The primary efficacy endpoint of BLISS-76 was the patient response rate at Week 52 as measured by the SLE Responder Index (SRI), which defines patient response by 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.

 

  • Week 52 (Primary Endpoint). Based on intention-to-treat (ITT) analysis, belimumab 10 mg/kg met its primary endpoint of superiority versus placebo at Week 52. A statistically significant improvement was shown in patient response rate for belimumab 10 mg/kg plus standard of care, vs. placebo plus standard of care, as measured by SRI at Week 52: 43.2% for 10 mg/kg belimumab, 40.6% for 1 mg/kg belimumab, and 33.5% for placebo (p=0.017 and p=0.089 for 10 mg/kg and 1 mg/kg belimumab, respectively vs. placebo).
  • Week 76 (Major Secondary Endpoint). At Week 76, belimumab plus standard of care showed higher response rates compared with placebo plus standard of care as measured by SRI; however, this major secondary endpoint did not reach statistical significance: 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).
  • Post hoc exploratory analyses at Weeks 52 and 76 evaluated SRI response using greater SELENA SLEDAI reductions (-5, -6, or -7 or more points) than the 4-point reduction used for the primary endpoint. These results along with the pre-specified 4-point reduction are provided below. Using these higher SELENA SLEDAI thresholds, a greater treatment effect was observed, with significant improvements in SRI response for the 10 mg/kg treatment group at both Week 52 and Week 76 (p<0.05 vs. placebo).
    SRI Rate at Week 52     SRI Rate at Week 76
SELENA
SLEDAI

 

  Placebo
N=275

 

  1 mg/kg
N=271

 

  10 mg/kg
N=273

 

    Placebo
N=275

 

  1 mg/kg
N=271

 

  10 mg/kg
N=273

 

‰¥4-point
reduction

 

  33.5%   40.6%   43.2%*     32.4%   39.1%   38.5%
‰¥5-point
reduction
  20.4%   31.0%**   32.6%***     21.8%   28.4%   30.8%*
‰¥6-point
reduction
  18.9%   28.8%**   30.8%**     20.4%   26.9%   28.9%*
‰¥7-point
reduction
N=649

 

  13.4%   19.4%   21.3%*     13.9%   21.7%*   21.8%*
                           
* p<0.05 **   p<0.01 ***   p<0.001

 

“Belimumab met the primary endpoint in both BLISS-76 and BLISS-52. The totality of Phase 3 data suggests that belimumab added to standard care offered improved clinical benefit versus standard of care alone, and was generally well tolerated in these studies,” said Ronald F. van Vollenhoven, M.D., Associate Professor of Rheumatology, Karolinska Institute, and Chief, Clinical Trial Unit, Karolinska University Hospital, Stockholm, Sweden. “The clinical design innovations in these Phase 3 studies may also encourage the development of future medicines for lupus.”

KEY BLISS-76 STUDY FINDINGS PRESENTED AT EULAR ALSO INCLUDED:

Disease Activity

 

  • At Week 52, the mean percent improvement in SELENA SLEDAI score was 36.0% for belimumab 10 mg/kg, 33.9% for belimumab 1 mg/kg, and 26% for placebo (p=0.0077 and p=0.040 for 10 mg/kg and 1 mg/kg belimumab, respectively vs. placebo). At Week 76, the mean percent improvement 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=0.014 and p=0.027 for 10mg/kg belimumab and 1 mg/kg belimumab, respectively vs. placebo).
  • The proportion of patients with a reduction in SELENA SLEDAI score of at least 4 points by Week 52, a major secondary endpoint, was 46.9% for belimumab 10 mg/kg, 42.8% for belimumab 1 mg/kg, and 35.6% for placebo (p=0.0062 and p=0.087 for belimumab 10 mg/kg and 1 mg/kg, respectively vs. placebo). At Week 76, the proportion of patients with a reduction in SELENA SLEDAI score from baseline 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).
  • The risk of severe SLE disease flares (SFI) was reduced over 76 weeks by 23% in the 10 mg/kg belimumab treatment group and by 34% in the 1 mg/kg belimumab treatment group vs. placebo (p=0.13 and p=0.023 for 10 mg/kg and 1 mg/kg belimumab, respectively). From Weeks 24-76, the risk of severe SLE disease flares was reduced by 30% in the 10 mg/kg belimumab treatment group and by 45% in the 1 mg/kg belimumab treatment group vs. placebo (p=0.10 and p=0.009 for 10 mg/kg and 1 mg/kg belimumab, respectively).
  • From Weeks 24-76, the risk of all SLE disease flares was significantly reduced in the belimumab 10 mg/kg treatment group, with risk reduction of 22% for 10 mg/kg belimumab and 16% for 1 mg/kg belimumab (p=0.016 and p=0.098 for 10 mg/kg and 1 mg/kg belimumab, respectively). Over 76 weeks from study initiation, however, the risk of all SLE disease flares (SFI) was not statistically different between the belimumab and placebo treatment groups.

Steroid Use

 

  • 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 from baseline to 7.5 mg per day or less by Week 76 was 25.8% for belimumab 10 mg/kg, 27.7% for belimumab 1 mg/kg, and 17.5%% for placebo (p=0.15 and p=0.046 for belimumab 10 mg/kg and 1 mg/kg, respectively, vs. placebo). One of the BLISS-76 study's major secondary endpoints was the percentage of these patients who – during Weeks 40-52 – had their average steroid dose reduced by at least 25% from baseline to 7.5 mg per day or less. These percentages were: 16.7% for belimumab 10 mg/kg, 19.2% for belimumab 1 mg/kg, and 12.7% for placebo, and were not statistically significant vs. placebo.
  • Among patients who were receiving ‰¤7.5 mg per day of prednisone at baseline (N=443), the percentage of patients who had their average steroid dose increased to >7.5 mg per day by Week 76 was 11.8% for belimumab 10 mg/kg, 13.5% for belimumab 1 mg/kg, and 18.1% for placebo (p=0.17 and p=0.33 for belimumab 10 mg/kg and 1 mg/kg, respectively, vs. placebo).

Fatigue

 

  • Numerically improved fatigue scores were observed in the belimumab treatment groups vs. the placebo group within 8-12 weeks, and the 1 mg/kg belimumab treatment group achieved statistically significant improvement of fatigue by Week 52, which was maintained at Week 76 (FACIT-Fatigue Scale; p<0.05 vs. the placebo group). Mean absolute FACIT-Fatigue improvement from baseline at Week 76 was 5.0 for belimumab 10 mg/kg, 5.2 for belimumab 1 mg/kg, and 3.2 for placebo (p=0.12 and p=0.036 for belimumab 10 mg/kg and 1 mg/kg, respectively, vs. placebo).

Biomarker Data

 

  • Among patients who were positive for anti-double-stranded DNA autoantibodies (anti-dsDNA) at baseline, a significantly greater median percent reduction in anti-dsDNA was observed among patients in the belimumab treatment groups vs. the placebo group, with reductions observed by Week 8 that were sustained or increased through Week 76. At Week 76, the median percent reduction in anti-dsDNA was 49.5% for belimumab 10 mg/kg, 43.3% for belimumab 1 mg/kg, and 9.7% for placebo (p<0.0001 for belimumab 10 mg/kg and 1 mg/kg, vs. placebo).
  • Among patients with low C4 complement at baseline, a significantly greater median percent increase was observed among patients in the belimumab treatment groups vs. the placebo group, with increases observed by Weeks 4-8 that were sustained or increased through Week 76. At Week 76, the median percent increase in C4 complement was 51.9% for belimumab 10 mg/kg, 38.5% for belimumab 1 mg/kg, and 16.7% for placebo (p<0.0001 and p=0.0002 for belimumab 10 mg/kg and 1 mg/kg, respectively, vs. placebo).

Safety

 

  • In BLISS-76 through 76 weeks, belimumab was generally well tolerated, with rates of adverse events overall, 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 7.7% of patients on belimumab and 8.4% 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. A total of seven malignancies were reported in BLISS-76: 2, 4, and 1 in the belimumab 10 mg/kg, belimumab 1 mg/kg and placebo groups, respectively. A total of three deaths were reported in the study: 1, 2, and 0 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. The data from the BLISS-76 Phase 3 study were analyzed after 52 weeks in accord with the study protocol, in support of the BLA and MAA submissions. The BLISS-76 study then continued for an additional 24 weeks through the full 76-week treatment period, with the objective of generating additional information about belimumab based on a variety of secondary endpoints. 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.

EULAR PRESENTATION OF KEY PHASE 2 FIVE-YEAR CONTINUATION DATA

The results through five years from a long-term Phase 2 continuation trial of belimumab will be presented at EULAR on Saturday, June 19, by W. Winn Chatham, M.D., Professor of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama School of Medicine, Birmingham. “The evidence of durability of belimumab's clinical effect over the course of five years in a long-term Phase 2 continuation study, together with the favorable safety profile observed in the study, suggests that belimumab may have potential for chronic use in the treatment of patients with seropositive SLE,” said Dr. Chatham.

The results showed that belimumab was associated with durable sustained improvement in disease activity across multiple clinical measures, decreased frequency of disease flares, and sustained reductions in autoantibody levels in seropositive patients with SLE. (All patients remaining on study after Week 52 received belimumab.) The data to be presented from Week 52 to Week 256 in seropositive patients with SLE who were treated with belimumab from initiation of the Phase 2 study include the following trends:

 

  • An increase from 46% to 59% in the SRI response rate selected as the primary efficacy endpoint of the Phase 3 trials (post hoc; intention-to-treat analysis).
  • A decrease from 62% to 22% in the overall frequency of SLE disease flares, as measured by the SELENA SLEDAI Flare Index.
  • A decrease from 23% to 11% in the frequency of patients experiencing a new BILAG A flare (which would indicate a severe flare of lupus disease activity) or more than one new BILAG B flare (which would indicate a moderate flare of disease activity).
  • An increase from 33% to 41% from Weeks 52-76 in mean percent improvement in PGA score, which was sustained from Weeks 76-256.

The biomarker data to be presented at EULAR from the Phase 2 continuation study through five years includes sustained reductions in a number of autoantibodies from Week 52 to Week 256 in seropositive patients who were treated with belimumab from initiation of the Phase 2 study. The median percent reductions from baseline among patients who were positive for the autoantibodies at baseline included:

 

  • Reduction in anti-dsDNA of 29.4% at Week 52 and 63.0% at Week 256.
  • Reduction in anti-Smith of 29.0% at Week 52 and 51.5% at Week 256.
  • Reduction in anti-cardiolipin IgG of 13.8% at Week 52 and 37.3% at Week 256.

The five-year Phase 2 continuation data to be presented at EULAR show belimumab was generally well tolerated in patients with SLE. By Week 256, overall belimumab exposure was 1,394 patient years. The incidence rates per 100 patients in all adverse event categories, including serious adverse events, overall adverse events, and serious infections, were similar for belimumab and placebo during the 52-week double-blind period, and remained the same or decreased over five years of continuous treatment. The overall incidence of adverse events (in general and by system organ class), serious adverse events, infections, malignancies and laboratory abnormalities decreased or stabilized over time from Week 52 to Week 256.

About the Phase 2 Study of BENLYSTA in SLE

The primary objectives of the Phase 2 study were to evaluate the efficacy and safety of belimumab (BENLYSTA) plus standard of care, versus placebo plus standard of care. A total of 449 patients with active SLE were randomized to receive one of three different doses of belimumab (1, 4 or 10 mg/kg) or placebo administered intravenously over a 52-week treatment period, in addition to standard-of-care therapy. At the end of 52 weeks, 345 patients chose to participate in an optional 24-week extension phase of the study, during which all patients received belimumab. At Week 76, 296 patients chose to remain on belimumab treatment in an open-label long-term continuation phase of the Phase 2 trial, in which all patients are receiving 10 mg/kg belimumab.

POSTER PRESENTATIONS AT EULAR OF DATA FROM BLISS-52 PHASE 3 STUDY

A separate press release also issued today highlights additional data to be presented at EULAR on Saturday, June 19, from the BLISS-52 Phase 3 trial of belimumab in patients with systemic lupus.

ABOUT BELIMUMAB

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 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.

ABOUT THE COLLABORATION WITH GSK

In August 2006, HGS and GSK entered into a definitive co-development and co-commercialization agreement under which HGS has responsibility for 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 current agreement.

ABOUT GLAXOSMITHKLINE

GSK Biopharm R&D is employing novel approaches to harness the therapeutic potential of biopharmaceuticals for the benefit of patients with serious autoimmune disease.

GlaxoSmithKline – one of the world's leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit 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.

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 medinfo@hgsi.com or by calling HGS at (877) 822-8472.

HGS, Human Genome Sciences, BENLYSTA, and ZALBIN 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.

 

Contact: HGS CONTACTS:
Media
Jerry Parrott, 301-315-2777
Vice President, Corporate Communications
or
Investors
Peter Vozzo, 301-251-6003
Senior Director, Investor Relations
or
GSK CONTACTS:
U.K. Media Inquiries -
Philip Thomson, (020) 8047-5502
Claire Brough, (020) 8047-5502
Stephen Rea, (020) 8047-5502
Alexandra Harrison, (020) 8047-5502
Jo Revill, (020) 8047-5502
or
U.S. Media Inquiries -
Holly Russell, 919-483-2839
Mary Anne Rhyne, 919-483-2839
or
European Analyst/Investor Inquiries -
David Mawdsley, (020) 8047-5564
Sally Ferguson, (020) 8047-5543
Gary Davies, (020) 8047-5503
or
U.S. Analyst/Investor Inquiries -
Tom Curry, 215-751-5419
Jen Hill Baxter, 215-751-7002

 

Posted: June 2010

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