Additional results from BLISS-76 Phase 3 trial of BENLYSTA presented at International Congress on SLE

Jun 28 2010

Human Genome Sciences, Inc. (Nasdaq:HGSI) today announced the presentation of additional results from BLISS-76, 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 Vancouver at the 9^th International Congress on Systemic Lupus Erythematosus on Friday and Saturday, June 25-26.

“Importantly, belimumab did not significantly affect the ability of SLE patients to maintain a protective response to vaccines, a finding that is consistent with the preservation of memory B-cells.”

"The BLISS-76 Phase 3 results presented at the International Congress on SLE include new data showing that belimumab treatment, consistent with its mechanism of action, resulted in selective and significantly greater reductions in levels of B-cell and plasma B-cell subsets, with significant preservation of memory B-cells," said William W. Freimuth, M.D., Ph.D., Vice President, Clinical Research - Immunology, Rheumatology and Infectious Diseases, HGS. "Importantly, belimumab did not significantly affect the ability of SLE patients to maintain a protective response to vaccines, a finding that is consistent with the preservation of memory B-cells."

KEY BLISS-76 FINDINGS PRESENTED AT THE INTERNATIONAL CONGRESS ON SLE

BLISS-76 Patient Response Rates (SRI)

BLISS-76 data recently presented at the 2010 Congress of the European League Against Rheumatism (EULAR) demonstrated that belimumab 10 mg/kg plus standard of care met the primary endpoint of the Phase 3 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. At Week 76, belimumab plus standard of care also 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.

• 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.
• Post hoc exploratory analyses of BLISS-76 data at Weeks 52 and 76 evaluated SRI response using greater SELENA SLEDAI reductions (-5, -6, -7, -8, -9 and -10 points) than the 4-point reduction used for the primary endpoint. 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). New data will be presented at the International Congress on SLE from analyses of SRI response using SELENA SLEDAI reductions of -8, -9, and - 10 points.

B-Cell Subsets

Belimumab acts by specifically recognizing, binding to, and inhibiting the biological activity of the naturally occurring protein BLyS (B-lymphocyte stimulator). 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 cells. The presence of autoantibodies appears to correlate with disease severity. In the BLISS-76 study, belimumab treatment resulted in selective and, vs. placebo, significantly greater median percent reductions in levels of B-cell and plasma B-cell subsets, with preservation of memory B-cells. The median percent changes from baseline included the following:

• Greater reductions in CD20+ cells were observed at Week 8 in both belimumab treatment groups, reached statistical significance by Week 24 and increased through Week 52 and Week 76 (all p<0.0001 for both belimumab doses vs. placebo).
• Significantly greater reductions in CD20+/CD27- naïve cells were observed at Week 8 in both belimumab treatment groups and increased through Weeks 24, 52 and 76 (all p<0.0001 for both belimumab doses vs. placebo).
• Greater reductions in CD20+/CD69+ activated cells were observed at Week 24 in both belimumab treatment groups, reached statistical significance for belimumab 10 mg/kg by Week 52 which was maintained through Week 76, and reached significance for belimumab 1 mg/kg by Week 76 (all p<0.05 vs. placebo).
• Greater reductions in CD20+/CD138+ plasmacytoid cells were observed at Week 8 in both belimumab treatment groups, reached statistical significance by Week 24 (p<0.05, vs. placebo), and increased or were maintained through Weeks 52 (p<0.001 vs. placebo) and 76 (p<0.001 and p<0.01 for belimumab 10 mg/kg and 1 mg/kg respectively vs. placebo).
• A significantly greater reduction in CD20-/CD138+ plasma cells was observed at Week 8 in the belimumab 10 mg/kg group, which was maintained through Weeks 24, 52 and 76 (all p<0.01 vs. placebo). In the belimumab 1 mg/kg group, the greater reduction reached statistical significance by Week 24 (p<0.05 vs. placebo); however, statistical significance for the lower dose was not maintained through Weeks 52 and 76).
• A significantly greater reduction in CD20-/CD27^BR short-lived plasma cells was observed at Week 8 in the belimumab 10 mg/kg group, which was maintained through Weeks 24, 52 and 76 (all p<0.01 vs. placebo). Greater reductions were also observed In the belimumab 1 mg/kg group, but the difference did not reach statistical significance.
• A significantly greater reduction in CD19+/CD27 ^BR/CD38^BR SLE subset cells was observed at Week 8 in the belimumab 10 mg/kg group (p<0.01 vs. placebo), which was maintained through Weeks 24, 52 and 76 (all p<0.001 vs. placebo). Greater reductions were also observed In the belimumab 1 mg/kg group, but the difference did not reach statistical significance.
• Significantly greater increases in CD20+/CD27+ memory cells were observed at Week 8 in both belimumab treatment groups and increased through Weeks 24, 52 and 76 (p<0.0001 at Weeks 8, 24 and 52, and p<0.05 at Week 76 for belimumab 10 mg/kg vs. placebo).

Effect on Protective Immune Response

• Belimumab did not significantly affect the ability of SLE patients to maintain a protective response to pneumococcal, tetanus and influenza vaccines, which is consistent with the preservation of memory B-cells.

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.