The monoclonal antibody for the treatment of moderate to severe rheumatoid arthritis is under investigation in phase III clinical trials.

GlaxoSmithKline (GSK) licensed the rights to otilimab, an anti-granulocyte macrophage colony-stimulating factor (anti GM-CSF) monoclonal antibody, from MorphoSys in 2013, paying $25.4 million — with additional payments forthcoming if the drug reached certain developmental milestones.

One of those milestones has been achieved (https://www.genengnews.com/news/gsk-advances-arthritis-candidate-into-phase-iii-triggering-e22m-milestone-payment-to-morphosys/); GSK has initiated a phase III program to investigate the safety and efficacy of opilimab for the treatment of patients with moderate to severe rheumatoid arthritis who have had an inadequate response to disease-modifying anti-rheumatic drugs (DMARD) or targeted therapies. As a result, MorphoSys has received a milestone payment of $24.9 million from GSK.

The phase III program includes studies of otilimab in three different trials, looking at comparisons to currently marketed therapies. In one trial, otilimab will be compared with a placebo and Pfizer’s Xeljanz^® (tofacitinib), all in combination with methotrexate (MTX). In another, otilimab will be compared with a placebo and with Xeljanz in combination with conventional synthetic DMARDs. The last trial will compare otlimab with a placebo and Kevzara^® (sarilumab), co-marketed by Sanofi Genzyme and Regeneron Pharmaceuticals, all in combination with conventional synthetic DMARDs.

Xeljanz is a JAK inhibitor approved for indications in rheumatoid arthritis, as well as psoriatic arthritis and ulcerative colitis. Kevzara is an interleukin-6 (IL-6) receptor antagonist indicated for adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more DMARDs.

The FDA has issued warnings regarding the safety of Xeljanz when taken in 10 mg doses twice daily because an increased risk of blood clots in the lungs and death was uncovered in a postmarketing study. The JAK inhibitor Olumiant^® (baricitinib), co-developed by Incyte and Eli Lilly, was approved but at a limited dose, also due to safety concerns.

Selective JAK1 inhibitors with anticipated improved safety profiles are currently being developed by Gilead Sciences (filgotinib) and AbbVie (upadacitinib) –– both could potentially be competition for otilimab.