Sanofi/Regeneron’s IL-6R Monoclonal Antibody Kevzara Shows Reduced Mortality in Critically Ill COVID-19 Patients in Phase II/III Trial

On April 27, Sanofi/Regeneron announced the preliminary Phase II results from the Phase II/III study of their IL-6R monoclonal antibody Kevzara (sarilumab) for the treatment of hospitalized COVID-19 patients with “severe” or “critical” respiratory disease.

This study enrolled 457 patients, of whom 28% had severe disease (requiring supplemental oxygen but not mechanical ventilation or high-flow oxygen), 49% had critical disease (requiring mechanical ventilation or high-flow oxygen in the ICU), and 23% had multiple organ dysfunction. The Phase II stage of the study employed a randomized design, primarily comparing the efficacy differences among intravenous Kevzara 400 mg, Kevzara 200 mg, and placebo.

Preliminary analysis results from the Phase II study showed that Kevzara treatment rapidly reduced C-reactive protein levels, meeting the primary endpoint. An increase in IL-6 levels from baseline was observed in all treatment groups, with a more pronounced elevation in critically ill patients compared to those with severe disease. No unexpected safety events related to Kevzara treatment were identified.

Exploratory analyses of clinical outcomes showed that Kevzara did not demonstrate benefit in improving treatment outcomes for patients with severe COVID-19; however, in patients with critical COVID-19, Kevzara treatment demonstrated benefit in improving clinical outcomes, reducing mortality and the proportion of patients requiring mechanical ventilation compared with the placebo group.

Based on the recommendation of the Independent Data Monitoring Committee (IDMC) following its review of all available data, the two companies decided to amend the trial protocol. Subsequent Phase III trials will enroll only patients with “critical” COVID-19, and the low-dose 200 mg arm has been discontinued; participants will receive either Kevzara 400 mg or placebo for treatment observation.

Dr. John Reed, Global Head of Research and Development at Sanofi, stated, “We are committed to addressing the global COVID-19 pandemic. As our understanding of this disease and how to better treat patients continues to grow, these preliminary results from randomized clinical trials provide additional guidance for physicians on the use of Kevzara. The application of Kevzara in the treatment of COVID-19 remains currently limited to clinical trials. We are still on the front lines of the fight against this disease, seeking additional means to overcome it, including the development of vaccines that can be produced at scale.”