ROCKVILLE, Md. & LONDON--(BUSINESS WIRE)--Human Genome Sciences, Inc. (Nasdaq:HGSI - News) and GlaxoSmithKline PLC (GSK) today announced that BENLYSTA™ (belimumab) met the primary endpoint in BLISS-76, the second of two pivotal Phase 3 trials in seropositive patients with systemic lupus erythematosus (SLE). BLISS-76 study results through 52 weeks showed that belimumab 10 mg/kg plus standard of care achieved a 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, 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.
“The BLISS-76 results confirm our view that BENLYSTA has the potential to become the first new approved drug in decades for people living with systemic lupus,” said H. Thomas Watkins, President and Chief Executive Officer, HGS. “We take great pride in the innovation and scientific rigor that has made it possible to bring BENLYSTA to this point. We plan to submit marketing applications in the first half of 2010, following discussions with regulatory authorities in the United States, Europe and other regions. We will continue to work with GSK to advance this drug to the market where it may benefit patients with significant need.”
Carlo Russo, M.D., Senior Vice President, Biopharm Development, GSK, said, “The results from this second pivotal Phase 3 trial reinforce our belief that belimumab could deliver a significant therapeutic option for patients with lupus who have had no new treatment in fifty years. We look forward to continuing our collaboration with HGS in order to bring this important medicine to patients.”
The data from the BLISS-76 study were 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. However, the BLISS-76 study is ongoing and will continue for 24 more weeks. Additional data will be available following completion of the full 76-week study period. 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 August 2006.
Key Findings from BLISS-76
“We are delighted that the efficacy of treatment with belimumab plus standard of care was superior to placebo plus standard of care in both BLISS-52 and BLISS-76, with overall adverse event rates comparable to placebo plus standard of care,” said David C. Stump, M.D., Executive Vice President, Research and Development, HGS. “Belimumab met the primary endpoint in both pivotal Phase 3 trials, as specified by the Special Protocol Assessment Agreement with FDA. We look forward to the full presentation of the BLISS-76 52-week results at an appropriate scientific meeting, hopefully in the first half of 2010.”
Topline BLISS-76 results include:
Based on an intention-to-treat (ITT) analysis, belimumab 10 mg/kg met its primary efficacy 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 the SLE Responder Index at Week 52: 43.2% for 10 mg/kg belimumab, 40.6% for 1 mg/kg belimumab, and 33.8% for placebo (p=0.021 and p=0.10 for 10 mg/kg and 1 mg/kg belimumab, respectively vs. placebo). The 1 mg/kg dose plus standard of care did not achieve statistically significant improvement in the current study. The SLE Responder Index defines patient response as 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.
Results for prespecified major secondary efficacy endpoints were:
The proportion of patients with a reduction in SELENA SLEDAI score of at least 4 points by Week 52, 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).
Improvement from baseline in Physician’s Global Assessment (PGA) at Week 24 was not statistically different between the belimumab and placebo treatment groups. Mean improvement in PGA at Week 52, a prespecified although not a major secondary endpoint, was 0.49 for belimumab 10 mg/kg, 0.55 for belimumab 1 mg/kg, and 0.46 for placebo (p=0.12 for belimumab 10 mg/kg and p=0.022 for 1 mg/kg, respectively vs. 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 study was 16.7% for belimumab 10 mg/kg, 19.2% for belimumab 1 mg/kg, and 12.7% for placebo (not statistically significant vs. placebo).
Improvement in health-related quality of life at Week 24 as measured by the SF-36 Physical Component Summary (PCS) score was not significantly different among treatment groups. Mean improvement in the SF-36 PCS score at Week 52, a prespecified although not a major secondary endpoint, was 3.41 for belimumab 10 mg/kg, 4.37 for belimumab 1 mg/kg, and 2.85 for placebo (p=0.51 for belimumab 10 mg/kg and p=0.012 for 1 mg/kg, respectively vs. placebo).
In BLISS-76, 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 26.8% of patients on belimumab and 24.0% of patients on placebo. Infections were reported in 72.1% of patients on belimumab and 67.3% of patients on placebo. Serious and/or severe infections were reported in 7.2% of patients on belimumab and 8.0% 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 7.2% in the belimumab treatment groups and 7.6% in the placebo treatment group. Malignancies were reported by 2, 3, and 1 subjects in the belimumab 10 mg/kg, belimumab 1 mg/kg and placebo groups, respectively. There were three deaths in the study, with 1, 2, and 0 reported in the belimumab 10 mg/kg, belimumab 1 mg/kg and placebo groups, respectively.
“The lupus community has waited for decades for one positive Phase 3 trial of an investigative drug developed for lupus. Now we have two. Based on the data we now have in hand, we have cause for hope that belimumab may emerge as a significant new treatment for lupus,” said Joan T. Merrill, M.D., a study investigator, Program Chair, Clinical Pharmacology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, and Professor, Department of Medicine, University of Oklahoma Health Sciences Center. |
