Pharma biz sources are buzzing with the PR news that belimumab (Benlysta*; GSK, Human Genome Sciences) improved the disease activity of systemic lupus erythematosus (SLE) in a 1-year, 2-dose, placebo-controlled, phase 3 study (BLISS-52). The mAb also enabled the reduction of the corticosteroid dosage.
The primary endpoint of the study, which was met with belimumab treatment, was a combination of 4 recognized measurements of SLE activity.** The reported patient response rates were 57.6% for belimumab 10 mg/kg; 51.7% for belimumab 1 mg/kg, and 43.6% for placebo (respective P values = .0006 and .011, vs placebo). All patients received “standard of care.” Individual secondary measures were also consistent with the statistically significant primary-endpoint results.
The rates of serious infections were 6.1% and 5.9% with belimumab and placebo, respectively, and rates of common adverse advents—headache, arthralgia, URI, UTI, and influenza—were also comparable between the 2 treatments. An important footnote in this relatively short-term study: no observed malignancies.
Results of a longer-term, placebo-controlled, phase 3 study with belimumab in SLE, BLISS-76, are expected in November (although the combined primary endpoint will be assessed at 52 weeks). As in BLISS-52, 2 belimumab dosages, 1 and 10 mg/kg, have been randomly assigned. Positive results will undoubtedly bolster a biologics license application to the FDA.
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 Human Genome Sciences, which entered into a codevelopment and comarketing agreement with GSK 3 years ago. Other anti-B-cell therapies in clinical development for SLE include rituximab (Rituxan; Genentech), epratuzumab (Immunomedics), and ocrelizumab (Genentech, Biogen) aka Son of Rituxan.
The most recent great hope for SLE, mycophenolate mofetil (CellCept; Roche) died a death of noninferiority, after it performed no better than cyclophosphamide for the induction treatment of lupus nephritis.
According to the Lupus Foundation of America, roughly 1.5 million Americans and more than 5 million people in the world have lupus.
mAb = monoclonal antibody; URI = upper respiratory tract infection; UTI = urinary tract infection.
* Formerly LymphStat-B.
** A reduction from baseline in the SELENA SLEDAI score of at least 4 points; no worsening in Physician Global Assessment (PGA); no new BILAG-A organ domain score; and no more than one new BILAG-B organ domain score from baseline.