GSK is pulling the plug on an experimental monoclonal antibody therapy for rheumatoid arthritis following a significant miss in one of three Phase III trials.
Courtesy of Leon Neal/Getty Images
GSK is pulling the plug on an experimental monoclonal antibody therapy for rheumatoid arthritis following a significant miss in one of three Phase III trials, the company announced Thursday.
GSK stated it was terminating the development of the anti-GM-CSF antibody otilimab after it failed to reach its primary endpoint in the Phase III ContRAst-3 study. Data from the ContRAst-3 trial did not reach statistical significance on the primary endpoint of ACR20, a composite measure of improvement in RA patients.
ACR20 is defined as a 20% improvement in multiple criteria, including tender and swollen joints and functional ability measures.
Otilimab is a monoclonal antibody that inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF), a protein that plays a central role in a broad range of immune-mediated diseases, including rheumatoid arthritis.
The overall ContRAst Phase III program enrolled a broad range of difficult-to-treat patients who had an inadequate response to or could not tolerate available treatments.
The Phase III trials began in 2019 with hopes that otilimab would benefit patients who have not found relief for their symptoms on widely available therapies, including JAK inhibitors, which have been under scrutiny due to safety concerns, particularly major adverse cardiac events.
The Phase III program aimed to improve on data seen in the Phase II BAROQUE trial.
The ContRAst-3 trial evaluated otilimab, which was licensed from MorphoSys in 2013, against placebo in patients who failed to respond adequately to Janus Kinase inhibitors, particularly Pfizer’s Xeljanz (tofacitinib) or against the anti-IL6 drug Kevzara (sarilumab), developed by Sanofi and Regeneron. The primary endpoint for each of the three ContRAst programs was the proportion of patients achieving ACR20 at week 12.
While otilimab failed in the ContRAst-3 study, the drug met the mark in the ContRAst-1 and ContRAst-2 trials. Full data from the three studies have not yet been shared, so it’s unknown at this point how otilimab fared against each control therapy.
Full results from the ContRAst phase III program are expected to be submitted for publication in 2023. Lyndsay Meyer, director of U.S. corporate communications for GSK, said the assessment of safety and efficacy data remains ongoing, but the limited efficacy demonstrated does not support a potential filing for regulatory approval.
“While the ContRAst-1 and ContRAst-2 trials met their primary endpoints, the efficacy demonstrated is unlikely to transform patient care for this difficult-to-treat patient population,” Meyer told BioSpace. “Based on analyses to date, GSK will not progress the development of otilimab in RA and does not expect to progress in other indications.”
