ADELPHI, MD. — Belimumab should be approved for reducing disease activity in adults with active autoantibody–positive systemic lupus erythematosus who are on standard treatment, a Food and Drug Administration advisory panel recommended in a 13-2 vote.
If approved, belimumab will be the first new treatment for systemic lupus erythematosus (SLE) in more than 50 years.
Currently, the only approved treatments for lupus are corticosteroids and hydroxychloroquine, approved in the 1950s, and aspirin.
At a Nov. 16 meeting of the FDA's Arthritis Drugs Advisory Committee, panelists strongly recommended that the drug's label stipulate the treatment was not evaluated in patients with active lupus nephritis or central nervous system manifestations of the disease.
Several panelists supporting approval pointed out that treatment effects were mild but agreed that the efficacy data supported approval.
Belimumab, a monoclonal antibody manufactured by Human Genome Sciences Inc., inhibits the biological activity of B-lymphocyte stimulator (BLyS), a cytokine that is elevated in patients with SLE and other autoimmune diseases.
The proposed dose is 10 mg/kg administered in an intravenous infusion at 2-week intervals for the first three doses and at 4 week intervals thereafter.
That treatment regimen was compared with a 1-mg/kg dose and placebo in two phase III randomized, placebo-controlled international studies of more than 1,600 patients (mean age 36-40 years) with active autoantibody-positive SLE.
The study participants were on standard immunosuppressive treatments. Most had musculoskeletal and mucocutaneous manifestations of SLE at baseline; those with kidney or CNS disease were excluded.
In both studies, a significantly greater proportion of patients on the 10-mg/kg dose met the primary end point – a combination of measures that indicated a reduction in disease activity – compared with those on placebo.
In one study, conducted primarily in Latin America and Asia, 58% of those on the 10-mg/kg dose met the primary end point, compared with 51% of those on the 1-mg/kg dose and 44% of those on placebo.
In the second study, conducted in North America and Western Europe, 43% of those on the 10-mg/kg dose met the primary end point, compared with 41% in the low-dose group and 34% in the placebo group.
There were more deaths, serious infections, and neurologic and psychiatric adverse events (including two suicides) among belimumab-treated patients in the phase III and earlier studies, although the numbers of these events was low.
Panelists were not overly concerned with these data, and agreed in a 14-1 vote that the safety profile of belimumab supported its approval. They strongly recommended that long-term safety should be followed in studies of a large number of patients.
The panel was concerned that in the trial that enrolled North American patients treatment was not effective in black patients and agreed with the company's plans to prospectively study responses in this population in postmarketing studies.
The FDA usually follows the recommendations of its advisory panels, members of which have been cleared of conflicts related to the meeting topic. If belimumab is approved, HGS plans to market it as Benlysta.