BLISS-SC, a new phase III trialto evaluate the efficacy, safety and tolerability of Benlysta (belimumab) administered subcutaneously (SC) once-weekly to autoantibody-positive adults with active systemic lupus erythematosus (SLE) has been initiated by GlaxoSmithKline (GSK) and Human Genome Sciences, Inc. (HGSI).
Belimumab is the first in a drug class known as BLyS-specific inhibitors. Belimumab was approved by the US Food and Drug Administration (FDA) on March 9, 2011 for the treatment of adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard therapy.
“Initiation of this new trial investigating a subcutaneous formulation of Benlysta represents an important step in our ongoing clinical development programme,” said H. Thomas Watkins, president and chief executive officer, Human Genome Sciences (HGS).
BLISS-SC is a phase III, multi-centre, international, randomised, double-blind, placebo-controlled, 52-week study to investigate use of belimumab administered subcutaneously once-weekly in autoantibody-positive adult subjects with active SLE.
Approximately 816 SLE subjects will be randomised to one of two arms, with a target of 544 subjects receiving belimumab 200 mg weekly plus standard of care (SOC) and 272 subjects receiving placebo plus SOC. Subjects completing the 52-week double-blind period can enter a 6-month open-label extension in which all subjects will receive belimumab 200 mg SC weekly.
The primary efficacy endpoint of BLISS-SC is response rate at week 52, as measured by the SLE Responder Index (SRI) defined as:
A reduction from baseline of at least 4 points on the SELENA-SLEDAI; and
No worsening (increase of <0.30 points from baseline) in Physician's Global Assessment (PGA); and No new BILAG A organ domain score (which would indicate a severe flare of lupus disease activity) or 2 new BILAG B organ domain scores (which would indicate a moderate flare of disease activity) compared with baseline at the time of assessment.
BLISS-SC is being conducted at over 200 sites globally. Initial results from the trial are anticipated in the second half of 2014. Data from this study will be subject to evaluation and approval by regulatory authorities before belimumab could be made available in a subcutaneous formulation.
In Europe, belimumab was approved by the European Commission on 13th July 2011. It is indicated as an add-on therapy in adult patients with active autoantibody-positive systemic lupus erythematosus, with a high degree of disease activity (e.g. positive anti-dsDNA and low complement), despite standard therapy. The summary of product characteristics (SmPC) lists patient groups which have not been studied with belimumab, including severe active CNS lupus or severe active lupus nephritis. Use of belimumab is therefore not recommended to treat these conditions. Caution should be exercised if belimumab is co-administered with other B cell targeted therapy or intravenous cyclophosphamide, as it has not been studied in combination with these agents.
HGS and GSK are developing belimumab under a definitive co-development and co-commercialization agreement entered into in 2006. Under the agreement, HGS had responsibility for conducting the belimumab phase 3 trials, with assistance from GSK. The companies share equally in phase 3/4 development costs, sales and marketing expenses, and profits of any product commercialized under the current agreement.
Benlysta is a registered trademark owned by Human Genome Sciences, Inc., used under license by the GlaxoSmithKline group of companies.