ROCKVILLE, Md. & LONDON--(BUSINESS WIRE)--Human Genome Sciences, Inc. (Nasdaq: HGSI - News) and GlaxoSmithKline PLC (GSK) today announced the full presentation of results from BLISS-52, the first of two pivotal Phase 3 trials of BENLYSTA™ (belimumab) in seropositive patients with systemic lupus erythematosus (SLE). The data, which will be presented today in Philadelphia at the 73rd Annual Scientific Meeting of the American College of Rheumatology (ACR), demonstrate that, in BLISS-52, belimumab plus standard of care achieved a clinically and 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 show that belimumab was generally well tolerated, with adverse event rates comparable between belimumab and placebo treatment groups.
“The BLISS-52 Phase 3 results presented at ACR demonstrate that the efficacy of treatment with BENLYSTA 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. “These data were statistically significant and were strongly supported across multiple measures of clinical effect and multiple time-points. Of note, a greater percentage of patients receiving BENLYSTA were able to reduce their use of steroids.”
Carlo Russo, M.D., Senior Vice President, Biopharm Development, GSK, said, “We have been pleased by the consistency of benefit demonstrated by belimumab in the BLISS-52 study, and we hope to confirm these results in the second Phase 3 study which is to report shortly. We very much hope that we will be able to deliver a new option for the treatment of this debilitating disease.”
Belimumab is an investigational drug and the first in a new class of drugs called BLyS-specific inhibitors. No new drug for lupus has been approved by regulatory authorities in more than 50 years. Belimumab is being developed by HGS and GSK under a co-development and commercialization agreement entered into in August 2006. Results from BLISS-76, the second Phase 3 trial of belimumab, will be announced on November 2, 2009. Assuming the results from BLISS-76 are positive, HGS and GSK plan to submit marketing applications in the United States, Europe and other regions in the first half of 2010.
Key Findings Presented at ACR from Phase 3 BLISS-52 Study
Professor Sandra V. Navarra, M.D., a principal investigator and Head of Rheumatology at the University of Santo Tomas, Manila, The Philippines, presented efficacy and safety results from the Phase 3 BLISS-52 study. “These data suggest that belimumab could emerge to play an important role in the future treatment of patients with SLE,” said Dr. Navarra. “Patients with SLE can experience a range of potentially debilitating symptoms, some of which can involve major organs and flare unpredictably several times during a year. For patients with severe symptoms, SLE can be fatal. It is a disease that represents a major unmet medical need. We are very encouraged by the BLISS-52 data and look forward to the results of the BLISS-76 study, which we hope will confirm the therapeutic potential of belimumab.”
Among 865 patients randomized and treated, belimumab met its primary efficacy endpoint by achieving a superior SLE patient response rate at Week 52 vs. placebo.
A clinically and statistically significant improvement was shown in patient 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 (p=0.0006 and p=0.013 for 10 mg/kg and 1 mg/kg belimumab, respectively).
The BLISS-52 patient response rate was based on the SLE Responder Index (SRI), which 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.
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).
The improvement in patient response rate was generally consistent across subgroups.
A dose response trend was observed, with a greater rate of patient response in the 10 mg/kg belimumab dose group.
Results for each individual component of the SRI strongly support the overall improvement shown for the primary endpoint.
Key findings of the BLISS-52 study also included the following:
FLARES
Belimumab significantly delayed time to first SLE disease flare versus placebo (SLE Flare Index/SFI): median = 119 days for 10 mg/kg belimumab, 126 days for 1 mg/kg belimumab, and 84 days for placebo (p=0.0036 and p=0.0026 for 10 mg/kg and 1 mg/kg belimumab, respectively vs. placebo).
The risk of having severe SLE disease flares (SFI) was reduced over 52 weeks by 43% in the 10 mg/kg belimumab treatment group and by 24% in the 1 mg/kg belimumab treatment group vs. placebo (p=0.0055 and p=0.1342 for 10 mg/kg and 1 mg/kg belimumab, respectively).
The risk of having 1 BILAG A (severe flare) or more than 1 BILAG B (moderate flare) organ domain score was reduced by 42% in the 10 mg/kg belimumab treatment group and by 13% in the 1 mg/kg treatment group vs. placebo (p=0.0016 and p=0.3722 for 10 mg/kg and 1 mg/kg belimumab, respectively).
DISEASE ACTIVITY
A significantly greater percentage of patients receiving belimumab achieved a reduction in SELENA SLEDAI score of at least 4 points by Week 52 (p=0.0024 and p=0.019 for 10 mg/kg and 1 mg/kg belimumab, respectively, vs. placebo), with improvement observed for 10 mg/kg belimumab within 4-8 weeks and reaching statistical significance at Week 16 and Weeks 24-52 (p<0.05 vs. placebo).
A significantly greater improvement in Physician’s Global Assessment (PGA) at Week 52 was observed in the belimumab treatment groups, with a mean percentage change from baseline of 45.7% for 10 mg/kg belimumab, 39.3% for 1 mg/kg belimumab, and 27.8% for placebo (p<0.0001 and p=0.004 for 10 mg/kg and 1 mg/kg belimumab, respectively, vs. placebo). The improvement in PGA was observed within 4-8 weeks and was sustained through 52 weeks (p<0.05 for both belimumab treatment groups).
STEROID USE
In patients who were receiving >7.5 mg per day of prednisone at baseline, a significantly higher percentage of patients in the 1 mg/kg belimumab treatment group vs. the placebo group had their average prednisone dose reduced by at least 25% from baseline to 7.5 mg per day or less during the last 12 weeks of study (p=0.025). A higher percentage of patients in the 10 mg/kg belimumab treatment group vs. the placebo group also had their average prednisone dose reduced by at least 25% from baseline to 7.5 mg per day or less during the last 12 weeks of study, but the difference did not reach a level of statistical significance (p=0.053).
In patients who were receiving =7.5 mg per day of prednisone at baseline, significantly fewer patients in the 10 mg/kg belimumab treatment group vs. the placebo group increased their prednisone use to >7.5 mg per day during the last 20 weeks of study (p<0.05). Fewer increases in prednisone use also were observed in the 1 mg/kg belimumab treatment group vs. the placebo group during the last 20 weeks of study, but the difference did not reach a level of statistical significance.
FATIGUE AND QUALITY OF LIFE
Improved fatigue scores were observed in the 10 mg/kg belimumab treatment group vs. the placebo group within 4-8 weeks, and both belimumab treatment groups achieved statistically significant improvement of fatigue by Week 52 (FACIT-Fatigue Scale; p<0.05 for both belimumab groups vs. the placebo group).
Improvement in health-related quality of life (HRQOL) as measured by the SF-36 Physical Component Summary (PCS) score at Week 24, a prespecified major secondary endpoint, was not significantly different among treatment groups. HRQOL improvement as measured by the SF-36 PCS score at Week 52 was significantly greater in both belimumab treatment groups vs. the placebo group (p=0.025 for 10 mg/kg and p=0.027 for 1 mg/kg belimumab, respectively).
SAFETY
In BLISS-52, belimumab was generally well tolerated, with rates of overall adverse events, serious adverse events, infections and fatalities comparable between belimumab and placebo treatment groups. Serious infections were reported in 5.9% of patients on placebo and 6.1% of patients on belimumab. The most common adverse events were headache, arthralgia, upper respiratory tract infections, urinary tract infection and influenza, and were also comparable between belimumab and placebo treatment groups. No malignancies were reported. |
