Trials Shows Efficacy of Otilimab in Moderate to Severe Rheumatoid Arthritis Not Statistically Significant

Otilimab did not demonstrate statistically significant efficacy in the third part of a phase 3 trial evaluating the medication in the treatment of moderate to severe rheumatoid arthritis (RA), according to a GSK press release.

An update to the ContRAst phase 3 program for otilimab, an investigational monoclonal antibody targeting granulocyte-macrophage colony-stimulating factor (GM-CSF) in moderate to severe RA, showed no statistical significance on the primary endpoint of ACR20 response versus placebo at week 12 in patients with inadequate response to biologic disease-modifying antirheumatic drugs (DMARDs) and/or Janus kinase inhibitors.

Otilimab inhibits GM-CSF, a protein that plays a central role in a broad range of immune-mediated diseases, including RA. Further, GM-CSF acts on cells, including microphages, that cause inflammation, joint damage, and pain. Otilimab also inhibits the biological function of GM-CSF by blocking the interaction of GM-CSF with its cell surface receptor.

RA is a chronic, systemic inflammatory condition that brings symptoms such as pain, swollen joints, stiffness, joint destruction, and disability. Although DMARDs are commonly used to treat RA, a substantial proportion of patients either fail to respond or show an inadequate response to these treatments, highlighting the need for more effective treatments that have alternative mechanisms of action.

The ContRast phase 3 program included a broad range of patients with difficult-to-treat RA who showed an inadequate response to or could not tolerate available treatments. In the ContRast-1 and ContRast-2 portions of the trial, the primary endpoints were met with a statistically significant ACR20 response versus placebo at week 12 in patients with an inadequate response to methotrexate (ContRAst-1) and conventional synthetic or biologic disease DMARDs (ContRAst-2).

The program was designed to analyze the efficacy and safety of 2 doses of otilimab at doses of 90 mg and 150 mg administered via subcutaneous weekly injections versus placebo, tofacitinib at 5 mg capsules twice daily, and sarilumab in 200 mg subcutaneous injections administered every other week, all in combination with methotrexate or conventional DMARDs.

The assessment of efficacy and safety data from the ContRAst program is ongoing, but the limited efficacy demonstrated does not support a suitable benefit/risk profile for otilimab as a potential treatment for RA, according to GSK.

REFERENCE

GSK provides update on ContRAst phase III programme for otilimab in the treatment of moderate to severe rheumatoid arthritis. GSK. October 27, 2022. Accessed October 28, 2022. https://www.gsk.com/en-gb/media/press-releases/gsk-provides-update-on-contrast-phase-iii-programme-for-otilimab-in-the-treatment-of-moderate-to-severe-rheumatoid-arthritis/