Rheumatology: November 2009 Archives
Another phase 3 trial of belimumab (Benlysta; Human Genome Sciences/GSK) in patients with systemic lupus erythematosus (SLE) has met its primary endpoint, according to a company press release. These data complement results of a previous phase 3 study, BLISS-52, in which the mAb (when compared with placebo) significantly improved disease activity* at 1 year.
Combined trial data will undoubtedly be used to support a biologics license application (BLA) to the FDA. Neither phase 3 study, however, has been published in a peer-reviewed journal.
In the placebo-controlled BLISS-76, belimumab 10 mg/kg significantly improved the SLE Responder Index** at 52 weeks (43.2% vs 33.8% with placebo; P = .021). However, the 1-mg/kg dose was not associated with statistically significant improvement. Outcomes of several secondary endpoints (eg, Physician's Global Assessment, reduction of corticosteroid dosage, SF-36 Physical Component Summary) also did not reach statistical significance.
Serious or severe infections were observed in 7.2% of patients who received belimumab and 8.0% of patients who received placebo. Rates of serious or severe infusion reactions were 1.1% with belimumab and 0.7% with placebo. Rates of discontinuation due to adverse events were 7.2% with belimumab and 7.6% with placebo. A handful of malignancies and deaths were also reported.
A comparison of the BLISS-52 and BLISS-76 results is provided here:
|
Outcome |
BLISS-52 |
BLISS-76 |
|
Primary endpoint (52 weeks) |
√ |
√ |
|
Belimumab 10 mg/kg, % |
57.6 |
43.2 |
|
Belimumab 1 mg/kg, % |
51.7 |
40.6 (NS) |
|
Placebo, % |
43.6 |
33.8 |
|
Secondary endpoints | ||
|
Reduction of SELENA SLEDAI score |
√ |
√ |
|
Belimumab 10 mg/kg, % |
58.3 |
46.9 |
|
Belimumab 1 mg/kg, % |
53.1 |
42.8 (NS) |
|
Placebo, % |
46.0 |
35.6 |
|
Improvement in PGA |
√ |
NS |
|
Reduction of corticosteroid dosage (≥25% to ≤7.5 mg/d) |
√ |
NS |
|
SF-36 Physical Component Summary |
NS |
NS |
|
Adverse events | ||
|
Serious infections |
|
|
|
Belimumab, % |
6.1 |
7.2 |
|
Placebo, % |
5.9 |
8.0 |
|
Infusion reactions |
|
|
|
Belimumab, % |
N/A |
1.1 |
|
Placebo, % |
N/A |
0.7 |
|
Discontinuation |
|
|
|
Belimumab, % |
N/A |
7.2 |
|
Placebo, % |
N/A |
7.6 |
Per protocol, BLISS-76 will continue for another 24 weeks, and according to the CEO of HGS, a BLA will likely be submitted to the FDA in the first half of next year.
Belimumab is a human mAb that inhibits the activity of B-lymphocyte stimulator (BLyS), which promotes the survival of (auto)antibody-producing B cells. The drug was discovered by HGS, which entered into a codevelopment and comarketing agreement with GSK in 2006. Other anti-B-cell therapies in clinical development for SLE include epratuzumab (Immunomedics) and ocrelizumab (Genentech, Biogen), aka Son of Rituxan.
A recent great hope for SLE, mycophenolate mofetil (CellCept; Roche) died a death of noninferiority after it performed no better than cyclophosphamide in the induction treatment of lupus nephritis. Rituximab (Rituxan) also flopped in a recent phase 3 study of lupus nephritis.
According to the Lupus Foundation of America, roughly 1.5 million Americans and more than 5 million people worldwide have lupus.
mAb = monoclonal antibody; N/A = not available; NS = not significant.
* Measured by using a combination of 4 recognized scales: a reduction of the SELENA SLEDAI score by at least 4 points from baseline; no worsening per the Physician's Global Assessment (PGA); no new BILAG-A organ domain score; and no more than 1 new BILAG-B organ domain score.
** The SLE Responder Index defines patient response as an improvement in the SELENA SLEDAI score by at least 4 points and no clinically significant decline per the BILAG score or PGA.
