Additional results from BLISS-52 Phase 3 trial of BENLYSTA for SLE to be presented at EULAR 2010

Jun 18 2010

Human Genome Sciences, Inc. (Nasdaq: HGSI) and GlaxoSmithKline PLC (GSK) today announced the presentation of additional results from BLISS-52, one of two pivotal Phase 3 trials of BENLYSTA® (belimumab) in seropositive patients with systemic lupus erythematosus (SLE). The additional data will be presented in Rome at the 2010 Congress of the European League against Rheumatism (EULAR) on Saturday, June 19.

“With both of the pivotal Phase 3 trials completed successfully, the results presented at major scientific meetings and regulatory applications now under review, we very much hope that we will be able to deliver a new option for the treatment of systemic lupus.”

"The BLISS-52 Phase 3 results presented at EULAR demonstrate that the efficacy of treatment in this study with belimumab 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. "Belimumab has met the primary endpoint in both of its pivotal Phase 3 trials. Earlier this month, we and GSK submitted marketing applications for belimumab in the United States and Europe. We now look forward to the consideration and conclusions of regulatory authorities."

Carlo Russo, M.D., Senior Vice President, Biopharm Development, GSK, said, "With both of the pivotal Phase 3 trials completed successfully, the results presented at major scientific meetings and regulatory applications now under review, we very much hope that we will be able to deliver a new option for the treatment of systemic 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 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.

KEY FINDINGS PRESENTED AT EULAR FROM THE BLISS-52 PHASE 3 STUDY

At EULAR on Saturday June 19, three poster presentations will provide results from the BLISS-52 Phase 3 trial of belimumab in seropositive patients with SLE.

BLISS-52 Patient Response Rates (SRI)

BLISS-52 data previously presented at the Annual Scientific Meeting of the American College of Rheumatology (ACR) in October 2009, demonstrated that belimumab plus standard of care met the primary endpoint of the study by achieving a statistically significant improvement in patient response rate as measured by the SLE Responder Index (SRI) at Week 52, compared with placebo plus standard of care.

• The SRI 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.
• A clinically and statistically significant improvement was shown in SRI 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>
• 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 (p<0.05 for both belimumab treatment groups).
• Post hoc exploratory analyses to be presented at EULAR evaluated SRI response in BLISS-52 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 improvements in SRI response for both belimumab treatment groups at Week 52.

Key BLISS-52 Findings Presented at EULAR

Steroid Use

• In patients who were receiving prednisone at baseline, a significantly higher percentage of patients in the 10 mg/kg belimumab treatment group vs. the placebo group had their average prednisone dose reduced by at least 50% from Weeks 24-52 (all p<0.05). A higher percentage of patients in the 1 mg/kg belimumab treatment group vs. the placebo group also had their average prednisone dose reduced by at least 50% after Week 24, but the difference reached a level of statistical significance only at Week 32>

Biomarker Data

• Among patients who were positive for autoantibodies at baseline, significantly greater median percent reductions in autoantibodies were observed in the belimumab treatment groups by Week 52, vs. placebo, including: reductions in anti-dsDNA of 37.6% for belimumab 10 mg/kg, 35.1% for belimumab 1 mg/kg, and 12.3% for placebo (p<0.001 for both doses); reductions in anti-Smith of 56.3% for belimumab 10 mg/kg, 47.0% for belimumab 1 mg/kg, and 29.6% for placebo>
• A significantly greater percentage of belimumab-treated patients with hypergammaglobulinemia at baseline achieved normalization of IgG at Week 52 (p<0.05). Significantly greater median percent reductions in immunoglobulins were observed in the belimumab treatment groups by Week 52 (with p<0.0001 for both belimumab doses, vs. placebo), including: reductions in IgG of 15.6% for belimumab 10 mg/kg, 14.1% for belimumab 1 mg/kg, and 3.6% for placebo; reductions in IgM of 30.0% for belimumab 10 mg/kg, 28.5% for belimumab 1 mg/kg, and 3.2%% for placebo; and reductions in IgA of 16.0% for belimumab 10 mg/kg, 16.8% for belimumab 1 mg/kg, and 2.7% for placebo.
• Among patients with low C3 and C4 complement at baseline, significantly greater median percent increases were 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 52. At Week 52, the median percent increase from baseline in C3 complement was 16.3% for belimumab 10 mg/kg, 10.1% for belimumab 1 mg/kg, and 2.1% for placebo (p<0.0001 and>

Additional BLISS-52 Efficacy Data

• Disease activity and flares: The EULAR presentation included BLISS-52 data previously presented at ACR, which demonstrated that belimumab 10 mg/kg also significantly reduced disease activity as measured by SELENA SLEDAI scores and Physicians Global Assessment (PGA); significantly delayed time to severe flare and significantly reduced the risk of 1 BILAG A (severe) organ flare or more than 1 BILAG B (moderate) organ flare.
• Fatigue and health-related quality of life (HRQOL): The EULAR presentation included previously presented BLISS-52 data, which demonstrated that, in both belimumab treatment groups vs. placebo, significantly greater improvements were achieved by Week 52 in FACIT-Fatigue scores and in SF-36 Health-Related Quality-of-Life Physical Component Summary (PCS), Physical Functioning and Bodily Pain scores.

Safety

• In BLISS-52, 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 18.5% of patients on belimumab and 16.7% of patients on placebo. Infections were reported in 67.6% of patients on belimumab and 63.8%% of patients on placebo. Serious and/or severe infections were reported in 6.2% of patients on belimumab and 6.3% of patients on placebo. Serious and/or severe infusion reactions were reported in 1.6% of patients on belimumab and 0.3% of patients on placebo. Discontinuations due to adverse events were 5.4% in the belimumab treatment groups and 6.6% in the placebo treatment group. No malignancies were reported. A total of 9 deaths were reported in the study: 4, 2, and 3 in the belimumab 10 mg/kg, belimumab 1 mg/kg and placebo groups, respectively.