GlaxoSmithKline (GSK) and Human Genome Sciences, Inc 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.
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 favourable 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, 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 analysed 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 commercialisation agreement entered into in 2006.
“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, 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 per cent for 10 mg/kg belimumab, 39.1 per cent for 1 mg/kg belimumab, and 32.4 per cent for placebo (p=0.13 and p=0.11 for 10 mg/kg and 1 mg/kg belimumab, respectively vs. placebo). The SRI 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.
Belimumab is an investigational human monoclonal antibody drug that specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator, or BLyS.
In 2006, GSK and HGS entered into a definitive co-development and commercialisation agreement under which HGS is conducting the belimumab Phase 3 trials, with assistance from GSK.
The mission of HGS is to apply great science and great medicine to bring innovative drugs to patients with unmet medical needs.