Human Genome Sciences 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)
ROCKVILLE, MA, USA | June 25. 2010 | Human Genome Sciences, Inc. (Nasdaq:HGSI – News) 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 9th International Congress on Systemic Lupus Erythematosus on Friday and Saturday, June 25-26.
“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 (included below).
| RI Rate at Week 52 | SRI Rate at Week 76 | |||||||||||||||||
| SELENA
SLEDAI
|
Placebo
N=275
|
1 mg/kg
N=271
|
10 mg/kg
N=273
|
Placebo
N=275
|
1 mg/kg
N=271
|
10 mg/kg
N=273
|
||||||||||||
| ≥4-point reduction |
33.5% | 40.6% | 43.2%* | 32.4% | 39.1% | 38.5% | ||||||||||||
| ≥5-point reduction |
20.4% | 31.0%** | 32.6%*** | 21.8% | 28.4% | 30.8%* | ||||||||||||
| ≥6-point reduction |
18.9% | 28.8%** | 30.8%** | 20.4% | 26.9% | 28.9%* | ||||||||||||
| ≥7-point reduction N=649
|
13.4% | 19.4% | 21.3%* | 13.9% | 21.7%* | 21.8%* | ||||||||||||
| ≥8-point reduction**** N=631
|
13.3% | 18.5% | 21.4%* | 12.9% | 19.9%* | 21.9%** | ||||||||||||
| ≥9-point reduction**** N=440
|
8.2% | 14.0% | 15.4% | 4.8% | 14.7%** | 15.4%** | ||||||||||||
| ≥10-point reduction**** N=420
|
8.6% | 13.9% | 15.4% | 5.0% | 14.6%** | 14.0%* | ||||||||||||
* p<0.05 ** p<0.01 *** p<0.001 **** New data
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-/CD27BR 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/CD38BR 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.
About the BENLYSTA (belimumab) Phase 3 Development Program
The Phase 3 development program for belimumab included two double-blind, placebo-controlled, multi-center Phase 3 superiority trials – BLISS-52 and BLISS-76 – to evaluate the efficacy and safety of belimumab plus standard of care, versus placebo plus standard of care, in seropositive (HEp-2 ANA ≥ 1:80 and/or anti-dsDNA ≥ 30 IU/mL) patients with SLE. Both BLISS-52 and BLISS-76 have now been completed. This is the largest clinical trial program ever conducted in lupus patients. BLISS-52 randomized and treated 865 patients at 90 clinical sites in 13 countries, primarily in Asia, South America and Eastern Europe. BLISS-76 randomized and treated 819 patients at 136 clinical sites in 19 countries, primarily in North America and Europe.
The design of the two trials was similar, but the duration of therapy in the two studies was different – 52 weeks for BLISS-52 and 76 weeks for BLISS-76. The data from the BLISS-76 Phase 3 study were analyzed after 52 weeks in accord with the study protocol, in support of the BLA and MAA submissions. The BLISS-76 study then continued for an additional 24 weeks through the full 76-week treatment period, with the objective of generating additional information about belimumab based on a variety of secondary endpoints. HGS designed the Phase 3 program for belimumab in collaboration with GSK and leading international SLE experts, and the program is being conducted under a Special Protocol Assessment agreement with FDA.
About BENLYSTA (belimumab)
Belimumab is an investigational human monoclonal antibody drug that specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator, or BLyS. BLyS is a naturally occurring protein discovered by HGS that is required for the development of B-lymphocyte cells into mature plasma B cells. Plasma B cells produce antibodies, the body’s first line of defense against infection. 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 healthy tissues. The presence of autoantibodies appears to correlate with disease severity. Preclinical and clinical studies suggest that belimumab can reduce autoantibody levels in SLE. The results of two pivotal Phase 3 trials, BLISS-52 and BLISS-76, suggest that belimumab can reduce SLE disease activity.
In June 2010, GSK submitted a Marketing Authorization Application to the European Medicines Agency, seeking approval to market belimumab in Europe for treatment of autoantibody-positive patients with SLE, and HGS submitted 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.
About the Collaboration with GlaxoSmithKline PLC (GSK)
In 2006, HGS and GSK entered into a definitive co-development and commercialization agreement under which HGS is conducting the belimumab Phase 3 trials, with assistance from GSK. The companies will share equally in Phase 3/4 development costs, sales and marketing expenses, and profits of any product commercialized under the agreement.
About Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a chronic, life-threatening autoimmune disease. Approximately five million people worldwide, including approximately 1.5 million in the United States, suffer from various forms of lupus, including SLE. Lupus can occur at any age, but appears mostly in young people ages 15 to 45. About 90 percent of those diagnosed with lupus are women. African-American women are about three times more likely to develop lupus, and it is also more common in Hispanic, Asian and American Indian women. Symptoms may include extreme fatigue, painful and swollen joints, unexplained fever, skin rash and kidney problems. Lupus can lead to arthritis, kidney failure, heart and lung inflammation, central nervous system abnormalities, inflammation of the blood vessels and blood disorders. No new drug for lupus has been approved by regulatory authorities in more than 50 years. For more information on lupus, visit the Lupus Foundation of America at www.lupus.org, the Lupus Research Institute at www.lupusresearchinstitute.org, the National Institute of Arthritis and Musculoskeletal and Skin Diseases at www.niams.nih.gov, or Lupus Europe at www.lupus-europe.org.
About Human Genome Sciences
The mission of HGS is to apply great science and great medicine to bring innovative drugs to patients with unmet medical needs. The HGS clinical development pipeline includes novel drugs to treat lupus, inhalation anthrax, hepatitis C and cancer.
For more information about HGS, please visit the Company’s web site at www.hgsi.com. Health professionals and patients interested in clinical trials of HGS products may inquire via e-mail to medinfo@hgsi.com or by calling HGS at (877) 822-8472.
HGS, Human Genome Sciences and BENLYSTA are trademarks of Human Genome Sciences, Inc. Other trademarks referenced are the property of their respective owners.
SOURCE: Human Genome Sciences, Inc.
