Human Genome Sciences, Inc (Rockville, Md), announced that its investigational drug for lupus, LymphoStat-Bâ„¢ (belimumab), failed to meet the overall primary efficacy endpoints of reducing the signs and symptoms of systemic lupus erythematosus at week 24 (as measured by SELENA SLEDAI) or increasing the time to first lupus flare over a 52-week treatment period in the largest ever placebo-controlled phase II trial for lupus.
A human monoclonal antibody, belimumab neutralizes the activity of B-lymphocyte stimulator, or BLySâ„¢, a protein required for B-lymphocytes to develop into mature plasma B cells.
In the multicenter double-blind dose-ranging trial, 449 patients with active lupus were randomized to receive one of three different doses (1, 4, or 10 mg/kg) of LymphoStat-B or placebo, administered intravenously for 52 weeks in addition to standard-of-care therapy.
LymphoStat-B showed statistically significant clinical effect in seropositive patients, a subgroup that represented 75% of the study's patient population. The drug also produced targeted and statistically significant reductions in both circulating CD20-positive B cells and anti-dsDNA autoantibodies in comparison to placebo. No dose response was observed, however.
The disappointing study data caused shares in the company (45 million shares) to plunge almost 30% in value.
In July 2005, following the report by Human Genome Sciences that LymphoStat-B met the primary efficacy and safety endpoints in a phase II clinical trial in patients with rheumatoid arthritis, GlaxoSmithKline (GSK) exercised its option under a June 1996 agreement to jointly develop and market LymphoStat-B with Human Genome Sciences. Under the terms of the agreement, the two parties will share equally in phase III/IV development costs. HGS officials have said that the decision to proceed with the lupus study will be made following further analysis of the data and in consultation with both GSK and the US Food and Drug Administration (FDA). A phase III trial for the drug is still being planned.
No significant new treatment for lupus has been approved by the FDA in almost 40 years. Despite the current setback, Genentech's rituximab (an anti-CD20 antibody) is in phase II/III trials for moderate-to-severe lupus, and Immunomedics has recently initiated phase III trials for epratuzumab (an anti-CD22 antibody). Both of these therapeutic approaches rely on the depletion of dysfunctional circulating B cell populations.
Also in development is Bristol-Myers Squibb's investigational drug abatacept (a first-in-class selective modulator of T-cell costimulation), which is in early-stage trials for lupus and investigational treatments based on the interleukin-6 receptor and CD40 ligand (CD154).
—A. Techman