Global Sarilumab Clinical Trial Program Begins for Patients with Severe COVID-19

A clinical program evaluating sarilumab (Kevzara, Sanofi and Regeneron) has started in patients hospitalized with a severe form of the novel coronavirus (COVID-19), according to the company.

Sarilumab is a fully human monoclonal antibody that inhibits the interleukin-6 (IL-6) pathway by binding and blocking the IL-6 receptor. IL-6 can play a role in driving the overactive inflammatory response in the lungs of patients who are severely or critically ill with COVID-19 infection, according to a press release.

Further, sarilumab is an injectable prescription medicine currently used to treat adult patients with moderately to severely active rheumatoid arthritis after at least 1 other disease-modifying antirheumatic drug has been used and did not work well or could not be tolerated.

The multi-center, double-blind phase 2/3 trial will begin at medical centers in New York and will assess the safety and efficacy of adding sarilumab to usual supportive care, compared with supportive care plus placebo.

To enter the trial, patients must be hospitalized with laboratory-confirmed COVID-19 that is classified as severe or critical, or who are suffering from multi-organ dysfunction. Patients will be assessed for 60 days or until hospital discharge or death. The group will be randomized 2:2:1 into 3 groups: sarilumab high dose, sarilumab low dose, and placebo. The primary endpoint is reduction of fever and the secondary endpoint is decreased need for supplemental oxygen.

The study is designed in 2 parts and is anticipated to enroll up to 400 patients. The first part will recruit patients with severe COVID-19 infection across approximately 16 US sites, evaluating the impact of sarilumab on fever and patients’ need for supplemental oxygen. The second part of the trial will evaluate the improvement in longer-term outcomes, including preventing death and reducing the need for mechanical ventilation, supplemental oxygen, and/or hospitalization.

Researchers feel that IL-6 may play a key role in driving the inflammatory immune response that causes acute respiratory distress syndrome (ARDS) in patients critically ill from COVID-19. Results from a single-arm, 21-patient Chinese trial found that patients with COVID-19 experienced rapidly reduced fevers and 75% of patients reduced their need for supplemental oxygen within days of receiving another IL-6 receptor antibody called tocilizumab. These results have led China to update its COVID-19 treatment guidelines and approve the use of the IL-6 inhibitor to treat patients with severe or critical disease.

"Data from China suggest that the IL-6 pathway may play an important role in the overactive inflammatory response in the lungs of patients with COVID-19,” said George D. Yancopoulous, MD, PhD, co-founder, President, and chief scientific officer of Regeneron, in a press release.

“Despite this encouraging finding, it's imperative to conduct a properly designed, randomized trial to understand the true impact. Our trial is the first controlled trial in the US to evaluate the effect of IL-6 inhibition prospectively in COVID-19 patients. In addition to our Kevzara program, Regeneron is also rapidly advancing a novel antibody cocktail for the prevention and treatment of COVID-19, which we hope to have available for human testing this summer. Collectively, these technologies expedite a typically years-long process into a matter of months. This same technology was applied to the Ebola virus, where our therapy, REGN-EB3, was shown to dramatically improve survival in infected patients last year."

REFERENCE

Sanofi and regeneron begin global Kevzara® (sarilumab) clinical trial program in patients with severe COVID-19 [news release]. Cambridge, Mass and Tarrytown, NY; Sanofi: March 16, 2020. http://www.news.sanofi.us/2020-03-16-Sanofi-and-Regeneron-begin-global-Kevzara-R-sarilumab-clinical-trial-program-in-patients-with-severe-COVID-19. Accessed March 17, 2020.