GSK begins phase III trial of Benlysta, rituximab combo in systemic lupus erythematosus

Belimumab and rituximab have different but potentially complementary mechanisms of action. This study will assess whether co-administration enhances the treatment effect of belimumab and provides sustained disease control, which could lead to clinical remission.

SLE is a chronic, incurable, autoimmune disease associated with a range of symptoms that can fluctuate over time, affecting almost any system in the body.

GSK immuno-inflammation research and clinical development global head Gijs van den Brink said: “We are delighted to start this study and evolve our research programme for belimumab in SLE. Belimumab has already demonstrated its consistent efficacy in reducing disease activity for patients with SLE, with four successful phase III trials.

“The underlying biology of the disease, combined with the results from a small investigator-sponsored study in severe refractory SLE, provide a strong scientific rationale for initiating this study.

“Our aim with this study is to assess whether the combination treatment will not only achieve a state of low disease activity, but potentially also achieve clinical remission in patients living with this chronic and unpredictable disease.”

At least 200 patients with active SLE indicated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K score of 6 or more will be randomised to receive either belimumab plus rituximab-placebo, plus standard therapy (control arm); belimumab plus rituximab, plus standard therapy (combination arm); or belimumab plus standard therapy (reference arm); the control and combination arms will have background immunosuppressants discontinued by Week 4 and all three arms will have a corticosteroid taper.

The primary endpoint of the study is disease control defined as a SLEDAI-2K score <2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <5 mg/day at Week 52.

Clinical remission (defined as a Clinical SLEDAI-2K score=0 at Week 64) and durable response (defined as maintenance of disease control achieved at Week 104) with no treatment other than antimalarials, are major secondary endpoints.

Safety and tolerability will also be assessed. The study is anticipated to complete in 2021.

Belimumab, a monoclonal antibody, is currently the only biologic medicine specifically approved to treat SLE anywhere in the world.