GlaxoSmithKline and Human Genome Sciences announce full presentation at ACR of positive phase 3 study results for Benlysta in systemic lupus erythematosus

Benlysta (belimumab) significantly reduced SLE disease activity, disease flare rates and fatigue; significantly delayed time-to-first SLE disease flare; reduced prednisone use and improved health-related patient quality of life in the BLISS-52 study

Issued: Tuesday 20 October 2009, London UK

GlaxoSmithKline PLC (GSK) and Human Genome Sciences, Inc. (Nasdaq: HGSI) today announced the full presentation of results from BLISS-52, the first of two pivotal Phase 3 trials of Benlysta™ (belimumab) in seropositive patients with systemic lupus erythematosus (SLE).  The data, which were presented today in Philadelphia at the 73^rd Annual Scientific Meeting of the American College of Rheumatology (ACR), demonstrated that, in BLISS-52, belimumab plus standard of care achieved a clinically and statistically significant improvement in patient response rate as measured by the SLE Responder Index at Week 52, compared with placebo plus standard of care.  Study results also showed that belimumab was generally well tolerated, with adverse event rates comparable between belimumab and placebo treatment groups.

“The BLISS-52 Phase 3 results presented at ACR demonstrated that the efficacy of treatment with Benlysta plus standard of care was superior to that of placebo plus standard of care,” said David C. Stump, M.D., Executive Vice President, Research and Development, HGS.  “These data were statistically significant and were strongly supported across multiple measures of clinical effect and multiple time-points.  Of note, a greater percentage of patients receiving Benlysta were able to reduce their use of steroids.”

Carlo Russo, M.D., Senior Vice President, Biopharm Development, GSK, said, “We have been pleased by the consistency of benefit demonstrated by belimumab in the BLISS-52 study, and we hope to confirm these results in the second Phase 3 study which is to report shortly.  We very much hope that we will be able to deliver a new option for the treatment of this debilitating disease.”

Belimumab is an investigational drug and the first in a new class of drugs called BLyS-specific inhibitors.  No new drug for lupus has been approved by regulatory authorities in more than 50 years.  Belimumab is being developed by HGS and GSK under a co-development and commercialisation agreement entered into in August 2006.  Results from BLISS-76, the second Phase 3 trial of belimumab, will be announced on 02 November 2009.  Assuming the results from BLISS-76 are positive, HGS and GSK plan to submit marketing applications in the United States, Europe and other regions in the first half of 2010.

Key Findings Presented at ACR from Phase 3 BLISS-52 Study

Professor Sandra V. Navarra, M.D., a principal investigator and Head of Rheumatology at the University of Santo Tomas, Manila, The Philippines, presented efficacy and safety results from the Phase 3 BLISS-52 study.  “These data suggest that belimumab could emerge to play an important role in the future treatment of patients with SLE,” said Dr. Navarra.  “Patients with SLE can experience a range of potentially debilitating symptoms, some of which can involve major organs and flare unpredictably several times during a year.  For patients with severe symptoms, SLE can be fatal.  It is a disease that represents a major unmet medical need.  We are very encouraged by the BLISS-52 data and look forward to the results of the BLISS-76 study, which we hope will confirm the therapeutic potential of belimumab.”

Among 865 patients randomised and treated, belimumab met its primary efficacy endpoint by achieving a superior SLE patient response rate at Week 52 vs. placebo.

• A clinically and statistically significant improvement was shown in patient response rate for belimumab plus standard of care vs. placebo plus standard of care:  57.6% for 10 mg/kg belimumab, 51.4% for 1 mg/kg belimumab, and 43.6% for placebo (p=0.0006 and p=0.013 for 10 mg/kg and 1 mg/kg belimumab, respectively).
• The BLISS-52 patient response rate was based on 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.
• There were more responders in the 10 mg/kg belimumab group compared to the placebo group between Weeks 4 and 8 of the study and this difference was statistically significant at Week 16 (p<0.05 for="" 10="" mg/kg="" belimumab="" vs.="" placebo). ="" the="" improvement="" was="" statistically="" significant and="" sustained for="" 10="" mg/kg="" and="" 1="" mg/kg="" belimumab="" from="" week="" 24 and="" week="" 28, respectively,="" through 52="" weeks=""></0.05><0.05 for="" both belimumab="" treatment=""></0.05>
• The improvement in patient response rate was generally consistent across subgroups. 
• A dose response trend was observed, with a greater rate of patient response in the 10 mg/kg belimumab dose group.
• Results for each individual component of the SRI strongly support the overall improvement shown for the primary endpoint.
  
  

Key findings of the BLISS-52 study also included the following:

FLARES

• Belimumab significantly delayed time to first SLE disease flare versus placebo (SLE Flare Index/SFI): median = 119 days for 10 mg/kg belimumab, 126 days for 1 mg/kg belimumab, and 84 days for placebo (p=0.0036 and p=0.0026 for 10 mg/kg and 1 mg/kg belimumab, respectively vs. placebo). 
• The risk of having severe SLE disease flares (SFI) was reduced over 52 weeks by 43% in the 10 mg/kg belimumab treatment group and by 24% in the 1 mg/kg belimumab treatment group vs. placebo (p=0.0055 and p=0.1342 for 10 mg/kg and 1 mg/kg belimumab, respectively).
• The risk of having 1 BILAG A (severe flare) or more than 1 BILAG B (moderate flare) organ domain score was reduced by 42% in the 10 mg/kg belimumab treatment group and by 13% in the 1 mg/kg treatment group vs. placebo (p=0.0016 and p=0.3722 for 10 mg/kg and 1 mg/kg belimumab, respectively).
  
  

DISEASE ACTIVITY

• A significantly greater percentage of patients receiving belimumab achieved a reduction in SELENA SLEDAI score of at least 4 points by Week 52 (p=0.0024 and p=0.019 for 10 mg/kg and 1 mg/kg belimumab, respectively, vs. placebo), with improvement observed for 10 mg/kg belimumab within 4-8 weeks and reaching statistical significance at Week 16 and Weeks 24-52 (p<0.05 vs.=""></0.05>
• A significantly greater improvement in Physician’s Global Assessment (PGA) at Week 52 was observed in the belimumab treatment groups, with a mean percentage change from baseline of 45.7% for 10 mg/kg belimumab, 39.3% for 1 mg/kg belimumab, and 27.8% for placebo (p<0.0001 and="" p="0.004" for="" 10="" mg/kg="" and="" 1="" mg/kg="" belimumab,="" respectively,="" vs.="" placebo). ="" the="" improvement="" in="" pga was="" observed within="" 4-8 weeks and="" was="" sustained through 52="" weeks=""></0.0001><0.05 for="" both belimumab="" treatment=""></0.05>
  
  

STEROID USE

• In patients who were receiving >7.5 mg per day of prednisone at baseline, a significantly higher percentage of patients in the 1 mg/kg belimumab treatment group vs. the placebo group had their average prednisone dose reduced by at least 25% from baseline to 7.5 mg per day or less during the last 12 weeks of study (p=0.025).  A higher percentage of patients in the 10 mg/kg belimumab treatment group vs. the placebo group also had their average prednisone dose reduced by at least 25% from baseline to 7.5 mg per day or less during the last 12 weeks of study, but the difference did not reach a level of statistical significance (p=0.053).
• In patients who were receiving 7.5 mg per day of prednisone at baseline, significantly fewer patients in the 10 mg/kg belimumab treatment group vs. the placebo group increased their prednisone use to >7.5 mg per day during the last 20 weeks of study (p<0.05).  fewer increases in="" prednisone use also were observed in="" the="" 1="" mg/kg="" belimumab="" treatment="" group vs.="" the="" placebo group during the="" last 20 weeks of="" study, but="" the="" difference did not="" reach a="" level of="" statistical=""></0.05). >
  
  

FATIGUE AND QUALITY OF LIFE

• Improved fatigue scores were observed in the 10 mg/kg belimumab treatment group vs. the placebo group within 4-8 weeks, and both belimumab treatment groups achieved statistically significant improvement of fatigue by Week 52 (FACIT-Fatigue Scale; p<0.05 for="" both belimumab="" groups vs.="" the="" placebo=""></0.05>
• Improvement in health-related quality of life (HRQOL) as measured by the SF-36 Physical Component Summary (PCS) score at Week 24, a prespecified major secondary endpoint, was not significantly different among treatment groups.  HRQOL improvement as measured by the SF-36 PCS score at Week 52 was significantly greater in both belimumab treatment groups vs. the placebo group (p=0.025 for 10 mg/kg and p=0.027 for 1 mg/kg belimumab, respectively).
  
  

SAFETY

• In BLISS-52, belimumab was generally well tolerated, with rates of overall adverse events, serious adverse events, infections and fatalities comparable between belimumab and placebo treatment groups.  Serious infections were reported in 5.9% of patients on placebo and 6.1% of patients on belimumab.  The most common adverse events were headache, arthralgia, upper respiratory tract infections, urinary tract infection and influenza, and were also comparable between belimumab and placebo treatment groups.  No malignancies were reported.
  
  

About the Benlysta (belimumab) Phase 3 Development Programme

The Phase 3 development programme for belimumab includes two double-blind, placebo-controlled, multi-centre 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. This is the largest clinical trial programme ever conducted in lupus patients.  BLISS-52 randomised and treated 865 patients at 90 clinical sites in 13 countries, primarily in Asia, South America and Eastern Europe.  BLISS-76 enrolled and randomised 826 patients at 133 clinical sites in 19 countries, primarily in North America and Europe.  The design of the two trials is similar, but the duration of therapy in the two studies is different – 52 weeks for BLISS-52 and 76 weeks for BLISS-76. The data from BLISS-76 will be analysed after 52 weeks in support of a potential Biologics License Application in the United States and Marketing Authorisation Applications in Europe and other regions.  HGS designed the Phase 3 programme for belimumab in collaboration with GSK and leading international SLE experts, and the programme is being conducted under a Special Protocol Assessment agreement with FDA.

The primary efficacy endpoint of BLISS-52 and BLISS-76 is the patient response rate at Week 52 based on 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 (ITT) and adjusted for baseline stratification factors, including SELENA SLEDAI score, proteinuria and race.

In each of the two Phase 3 trials, patients were randomised to one of three treatment groups: 10 mg/kg belimumab (BLISS-52, n=290), 1 mg/kg belimumab (BLISS-52, n=288), or placebo (BLISS-52, n=287). Patients are dosed intravenously on Days 0, 14 and 28, then every 28 days thereafter for the duration of the study. All patients receive standard of care therapy in addition to the study medication. Safety is reviewed by an independent Data Monitoring Committee throughout both studies.

About Benlysta (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.  BLISS 52 results suggest that belimumab can reduce SLE disease activity.  Results from a second Phase 3 trial, BLISS-76, are expected on November 2, 2009.

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 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. 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 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.  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 improving 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 hepatitis C, lupus, inhalation anthrax and cancer.

The Company’s primary focus is rapid progress toward the commercialization of its two lead drugs, Benlysta™ (belimumab) for lupus and ZALBIN™ (albinterferon alfa-2b, formerly Albuferon®) for hepatitis C.  Benlysta has successfully met its primary endpoint in the first of two Phase 3 trials in systemic lupus erythematosus, and results of the second Benlysta Phase 3 trial are expected in November 2009.  ZALBIN has now completed Phase 3 development, and the submission of global marketing applications is expected in late fall 2009.  In May 2009, HGS submitted a Biologics License Application to the FDA for raxibacumab for the treatment of inhalation anthrax.  In addition, HGS has substantial financial rights to certain products in the GSK clinical pipeline including darapladib, currently in Phase 3 development in patients with coronary heart disease, and Syncria® (albiglutide), currently in Phase 3 development in patients with 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 medinfo@hgsi.com or by calling HGS at (877) 822-8472.