Benlysta (belimumab): A New Lupus Medication on the Horizon

The Study: BLISS-52

On July 20, 2009, Human Genome Sciences and GlaxoSmithKline announced positive results from their Phase-III, double-blind, placebo-controlled lupus clinical trial.

This 52-week study, also known as BLISS-52, enrolled 865 patients in 13 countries outside North America and randomized active lupus patients to 10mg/kg active drug (Belimumab, also known as Benlysta), 1 mg/kg active drug, or placebo (not containing active drug) in addition to their standard lupus medications.

Patients had to fulfill the American College of Rheumatology lupus criteria, have active lupus, and remain on a stable treatment regimen (excluding other biologic therapies or cyclophosphamide) in order to be eligible for the trial. Patients with severe lupus kidney disease and lupus-related neurologic problems were excluded. The study medication was given intravenously (through the veins) two weeks apart for the first two doses, and then every four weeks.

The study was successful in meeting its predetermined primary outcome, which was the percentage of patients with improvement by four or more points in their SELENA SLEDAI score (a validated composite clinical index measuring lupus activity in various organs) without worsening in two other clinical instruments for disease activity (physician global assessment (PGA) and BILAG (another clinical index to measure disease activity).

The response rates were 57.6%, 51.7% and 43.6% for Benlysta 10mg/kg, 1 mg/kg, and placebo, respectively (the response rates were significantly better in the active drug arms). In addition to improvement in various clinical measurements of disease activity, patients were also able to reduce steroid dosages. Notably, the drug was tolerated well and the safety profile, including the infection rate, was comparable to the placebo arm.

The Medication: Benlysta

Benlysta is a fully human monoclonal antibody that blocks the activity of a protein called B lymphocyte stimulator (BLyS). This protein has the ability to activate B-cells to produce autoantibodies (antibodies against self), which promote tissue damage in lupus.

What does this mean for patients and their physicians?

The study findings show that Benlysta has the potential to become the first new approved lupus drug in decades for people living with lupus. The findings are exciting for both lupus patients and physicians, given that there is currently a paucity of medications that are both safe and effective for lupus.

Based on the information we have from the study, Benlysta is likely to be used to treat patients with lupus that have an inadequate response to one or more of currently available drugs, such as hydroxychloroquine, mycophenolate mofetil, and/or azathioprine. It is unknown at this point whether Benlysta will also be effective in Lupus Nephritis and lupus affecting the nervous system, two of the most severe manifestations of lupus.

The developer of Benlysta, Human Genome Sciences, is sharing development and marketing of the drug with GlaxoSmithKline. They conducted a second Phase-III trial (BLISS-76, conducted in North America and Europe, in which Hospital for Special Surgery was one of the participating centers). The companies are planning to apply for regulatory approval in the first half of next year. 

ADDENDUM:

BLISS- 76: The Second Benlysta Trial Also Succeeded in Meeting Its Primary Endpoint

The results of BLISS-76 were announced on November 2, 2009. This trial took place in North America and Europe, and was identical in design to the BLISS-52 trial, except for the fact that the study period was 76 weeks. There were 275 patients in the placebo arm, 271 in the Belimumab 1mg/Kg arm, and 273 in the Belimumab 10 mg/Kg arm. Similar to BLISS-52, only patients with positive serology for ANA (= 1:80 titer) and/or anti-dsDNA autoantibodies were included in the trial.

The primary outcome was the percentage of patients that responded by the SLE Responder Index (defined as improvement by four or more points in their SELENA SLEDAI score without clinically significant worsening in the physician’s global assessment and BILAG) at week 52. The response rates were 43.2%, 40.6% and 33.8% for Benlysta 10mg/kg, Benlysta1 mg/kg, and placebo, respectively. Only the higher dose of Benlysta was significantly more effective than placebo.

Secondary outcomes, including ability to reduce steroid dosage also favored the active drug but were not as strong as in the BLISS-52 trial. The drug was tolerated well and its safety profile, including the infection rate, was comparable to the placebo arm.

The positive results of both Benlysta trials are welcomed by the rheumatology community as a big step forward in the treatment of lupus. Based on these trials, it is expected that the FDA will approve this drug for SLE in the near future, which is exciting news for patients and physicians. Even more importantly, these trials have opened the way for better designed lupus clinical trials and it is expected that other novel therapeutic agents will follow suit soon.

Sources

• Human Genome Sciences. July 20, 2009. “Human Genome Sciences and GlaxoSmithKline Announce Positive Phase 3 Study Results for Benlysta.” 
http://www.hgsi.com/latest/human-genome-sciences-and-glaxosmithkline-announce-positive-phase-3-study-results-for-benl-3.html

• Human Genome Sciences. November 2, 2009. “Human Genome Sciences and GlaxoSmithKline Announce Positive Results in Second of Two Phase 3 Trials of Benlysta™ in Systemic Lupus Erythematosus.”
http://www.hgsi.com/latest/human-genome-sciences-and-glaxosmithkline-announce-positive-results-in-second-of-two-phase-3-trials-of-benlysta-in-systemic-lupus-erythema.html