PARIS, France—The humanized monoclonal antibody belimumab, which previously failed to meet its primary efficacy endpoint in a phase II clinical trial for systemic lupus erythematosus (SLE), showed significant activity in the extension phase of that study as measured by new, FDA-approved assessment criteria.¹

Richard A. Furie, MD, director of the systemic lupus erythematosus and autoimmune disease treatment center at North Shore University Hospital Long Island Jewish Health System in Lake Success, NY reported 3-year results showing that belimumab (LymphoStat-B^®, Human Genome Sciences, Inc) is associated with sustained improvement in SLE disease activity as a reduction in the frequency of flares. Belimumab is a fully human monoclonal antibody that binds to the common growth factor B-lymphocyte stimulator (BLyS), a novel strategy for the treatment of inflammatory diseases such as SLE.

In the original phase II trial, the primary efficacy endpoint was SELENA-SLEDAI, the SELENA modification of the SLE disease activity index. For the current report, the authors used a new composite endpoint they call the SLE responder index, which has been recognized by the FDA as an SLE disease assessment tool.

The SLE responder index is based on the following criteria:

• An SELENA-SLEDA improvement of ≥4
• No new BILAG 1A or 2B flares
• No worsening on the physicians global assessment

A total of 449 patients with SLE with SELENA SLEDAI >4 were enrolled in a 52 week double-blind trial of belimumab at 1, 4, or 10 mg/kg monthly, or placebo. All patients who were on placebo at week 56 became eligible for high-dose belimumab 10 mg/kg; patients already receiving belimumab remained on their current dose or increased to 10 mg/kg, at the discretion of the investigators. All patients who remained in the study at 76 weeks (296 patients) then received 10 mg/kg in a continuation trial.

Dr. Furie presented data patients who were seropositive at baseline, as defined by an ANA >1:80 or anti-dsDNA antibodies >30 IU; 72% of study patients met this definition.

The investigators used the SLE flair index to determine the percentage of subjects who had at least one flare during each of the 6-month treatment periods. Dr. Furie et al combined belimumab dose groups for the analysis, because there is no dose-dependent effect of the antibody.

Among all seropositive patients treated with belimumab, the SLE responder index rates as a percentage were as follows:

    46% at 52 weeks (a difference of 29% over placebo, P <.05)
    49% at 56 weeks
    55% at 76 weeks
    55% at 160 weeks (intention-to-treat analysis)

“In seropositive subjects, belimumab treatment resulted in sustained improvement in SLE disease activity through 3 years of continuous treatment. The frequency of flares, as measured by the SLE flare index, declined in the 3 years that subjects remained on belimumab therapy,” Dr. Furie commented.

There are currently two phase III studies with belimumab, involving>1600 patients. Human Genome Sciences expects to report preliminary 52-week trial data in mid-2009.

Reference

1. Furie, RA, Petri M, Weisman MH, et al. Belimumab (fully human monoclonal antibody to Blys) improved or stabilized systemic lupus erythematosus (SLE) disease activity and reduced flare rate during 3 years of therapy. Presented at: EULAR 2008; June 11-14, 2008; Paris, France. Abstract OP-0017.