GSK Halts Development of Anti-GM-CSF Monoclonal Antibody Otilimab for COVID-19 Following Phase 2 Clinical Failure

Compiled & Translated by | newborn

According to a report by FierceBiotech, GlaxoSmithKline (GSK) has decided to discontinue the clinical development of the antibody drug otilimab for COVID-19. This decision is driven by two factors: the failure of otilimab in a Phase 2 clinical trial, and the progress of the company's anti-SARS-CoV-2 antibody pipeline. Currently, the clinical program evaluating otilimab for rheumatoid arthritis (RA) remains ongoing.

Otilimab is a fully human monoclonal antibody that targets, binds to, and inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF), a protein that plays a central role in a wide range of immune-mediated diseases, including RA. Otilimab neutralizes the biological activity of GM-CSF by blocking its interaction with cell surface receptors. In COVID-19, evidence indicates that GM-CSF is associated with clinical deterioration in patients. Therefore, otilimab has the potential as a treatment for COVID-19.

In February this year, GSK announced the results of the Phase 2 OSCAR clinical trial. The study enrolled COVID-19 patients with severe COVID-19-related lung disease who required high levels of oxygen support or early invasive mechanical ventilation. Data showed that across all age groups, compared with standard of care (including antiviral therapy and glucocorticoids), treatment with a single dose of otilimab plus standard of care failed to increase the likelihood of survival without respiratory failure at 28 days (the primary endpoint) in patients with severe COVID-19-related lung disease. However, a pre-specified analysis of 180 patients aged 70 years and older yielded encouraging results: 65.1% of patients in the otilimab group met the primary endpoint criteria, compared with 45.9% in the control group; additionally, the mortality rate was lower in the otilimab group (26% vs. 40.4%).

Encouraged by signs of efficacy, GSK decided to amend the OSCAR study to enroll an additional 350 patients aged 70 years and older to evaluate the efficacy of otilimab in this population, completing the study during the summer. Although GSK has not yet shared data from this expanded cohort, the company concluded that the ongoing evolution of the COVID-19 pandemic, coupled with the overall progress of its COVID-19 program, does not support further investigation of otilimab for COVID-19.

In its third-quarter financial report, GSK stated: "Growing evidence demonstrates that Xevudy (sotrovimab) plays a critical role in the treatment of mild to moderate COVID-19 among high-risk adult and pediatric patients. Given the ongoing evolution of the pandemic, the decision has been made to generate additional data on this drug. Consequently, it has been decided to discontinue further exploration of otilimab as a potential treatment for severe pulmonary COVID-19-related disease."

Xevudy is a single-dose anti-SARS-CoV-2 monoclonal antibody co-developed by GSK and Vir Biotechnology. It has currently been granted Emergency Use Authorization in multiple countries, including the United States, for the treatment of adults and adolescents (aged 12 years and older and weighing ≥40 kg) who test positive for SARS-CoV-2 and are at high risk of progression to severe COVID-19 (including hospitalization and death). Additionally, binding agreements have been signed for the sale and supply of over 420,000 doses of Xevudy.

Although GSK has decided to discontinue the development of otilimab for COVID-19, the company continues to investigate the drug for RA. Currently, the Phase 3 clinical trial for this indication is ongoing, with data expected in the second half of next year.

Source: GSK, after pushing past midphase fail, ends development of otilimab in COVID-19