Positive results from pivotal Phase 3 trials of BENLYSTA in SLE patients

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 BENLYSTA™ (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.

“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”

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 placebos 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>
  • 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>
  • 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>
  • 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>
  • 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.