Sanofi and Regeneron Pharmaceuticals have announced their global clinical trials of sarilumab (Kevzara) in treating patients with severe COVID-19; the US-based trials have been initiated and will start enrolling patients immediately.
The US phase 2/3 trial will be introduced in New York medical centers; New York is 1 of the states that have been hit hardest by the COVID-19 pandemic, with the number of confirmed cases approaching 1000 at the time of this article’s publication. The state has experienced 10 deaths from the outbreak and no recovered patients.
Sarilumab is a fully-human monoclonal antibody that inhibits the interleukin-6 (IL-6) pathway by binding and blocking the IL-6 receptor. A single-arm, 21-patient, non-peer-reviewed study in China provided preliminary data that support the capacity of IL-6 in enabling the overactive inflammatory response in the lungs of those severely or critically infected by COVID-19. The results showed rapidly reduced fevers and 75% (15 out of 20) of patients experienced a reduced need for supplemental oxygen within days of receiving tocilizumab, another IL-6 receptor antibody. These results have driven the approval of using the IL-6 inhibitor for severe or critical infection in China.
The multi-center, double-blind, phase 2/3 trials taking place in the United States will evaluate the safety and efficacy of including sarilumab in usual supportive care against supportive care plus placebo. The dynamic 2-part design of the trial aims to enroll up to 400 patients with COVID-19 infection. Part 1 will analyze sarilumab’s efficacy in treating fever and the need for supplemental oxygen in infected patients; part 2, the larger portion of the trial, aims to assess how to advance longer-term outcomes such as death prevention and reducing the need for mechanical ventilation, supplemental oxygen, and/or hospitalization.
John Reed, MD, PhD, Sanofi’s Global Head of Research and Development, outlined the significance of the trials in combatting the current pandemic. “At Sanofi, we are taking a leading role in addressing the global challenge of COVID-19 disease,” he said in a statement. “Scientific evidence has emerged to suggest the Kevzara may be a potentially important treatment option for some patients, and this trial will provide the well-controlled, rigorous scientific data we need to determine if IL-6 inhibition with Kevzara is better than current supportive care alone. Additionally, we expect to rapidly initiate trials outside the US in the coming weeks, including areas most affected by the pandemic such as Italy.”
"To initiate this trial quickly, Regeneron and Sanofi have worked closely with the US Food and Drug Administration and the Biomedical Advanced Research and Development Authority, otherwise known as the FDA and BARDA ," said George D. Yancopoulos, MD, PhD, co-founder, president and chief scientific officer of Regeneron. "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. 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.”
1. Sanofi and Regeneron begin global Kevzara (sarilumab) clinical trial program in patients with severe COVID-19 [news release]. Sanofi’s website. http://www.news.sanofi.us/2020-03-16-Sanofi-and-Regeneron-begin-global-K.... Accessed March 17, 2020.