Sanofi and Regeneron to Scale Back Late-Stage Trial of Kevzara after Negligible Results

The trial evaluating Kevzara (sarilumab), an interleukin-6 (IL-6) receptor antibody, in hospitalized patients with "severe" or "critical" respiratory illness caused by COVID-19, will be immediately amended so that only "critical" patients continue to be enrolled to receive Kevzara 400 mg or placebo.

This announcement was made by Sanofi S.A. (Paris, France) and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY, USA) following the preliminary results from the Phase 2 portion of an ongoing Phase 2/3 trial evaluating Kevzara. The randomized Phase 2 portion of the trial compared intravenously-administered Kevzara higher dose (400 mg), Kevzara lower dose (200 mg) and placebo. It assessed 457 hospitalized patients, who were categorized at baseline as having either "severe" illness (28% of patients), "critical" illness (49% of patients) or "multi-system organ dysfunction" (MSOD) (23% of patients). Patients were classified as "severe" if they required oxygen supplementation without mechanical or high-flow oxygenation; or "critical" if they required mechanical ventilation or high-flow oxygenation or required treatment in an intensive care unit.

Preliminary analysis of the Phase 2 portion of the trial demonstrated that Kevzara rapidly lowered C-reactive protein (CRP), a key marker of inflammation, meeting the primary endpoint. Baseline levels of IL-6 were elevated across all treatment arms, with higher levels observed in "critical" patients compared to "severe" patients. Additionally, no new safety signals were observed with the use of Kevzara in COVID-19 patients.

Analysis of clinical outcomes in the Phase 2 trial was exploratory and pre-specified to focus on the "severe" and "critical" groups. In the preliminary Phase 2 analysis, Kevzara had no notable benefit on clinical outcomes when combining the "severe" and "critical" groups, versus placebo. However, there were negative trends for most outcomes in the "severe" group, while there were positive trends for all outcomes in the "critical" group. Subsequent to the IDMC review, Regeneron and Sanofi reviewed the discontinued "severe" group data, which revealed that the negative trends in the Phase 2 trial (n=126) were not reproduced in Phase 3 trial (n=276), and that clinical outcomes were balanced across the Kevzara and placebo treatment arms. Outcomes for the "severe" group were better than expected based on prior reports, regardless of treatment assignment: for example, in the Phase 2 portion, approximately 80% were discharged, 10% of patients died and 10% remain hospitalized.

“Emerging evidence with Kevzara and other repurposed drugs in the COVID-19 crisis highlight the challenges of making decisions about existing medicines for new viral threats using small, uncontrolled studies,” said George D. Yancopoulos, M.D., Ph.D., Regeneron Co-Founder, President and Chief Scientific Officer. “We await results of the ongoing Phase 3 trial to learn more about COVID-19, and better understand whether some patients may benefit from Kevzara treatment. In addition, there is an acute need for tailored approaches that specifically target this virus. To that end, Regeneron is rapidly advancing our targeted anti-SARS-CoV-2 antibody cocktail and we plan to initiate clinical trials in June.”

“As we quickly follow the science to better understand this disease and explore how to best treat patients, these initial results from the randomized clinical trial setting provide physicians much needed insights and information regarding the potential of Kevzara for patients with COVID-19 treatment,” said John Reed, M.D., Ph.D., Sanofi's Global Head of Research and Development. “While our evaluation of the use of Kevzara for COVID-19 treatment remains an investigational approach, Sanofi continues to stay at the forefront of multiple initiatives to fight this disease, including researching other potential treatment options, developing vaccine candidates that can be manufactured at large-scale, and a potential collaboration for an innovative SARS-CoV-2 smartphone-based self-testing solution.”

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Sanofi S.A.
Regeneron Pharmaceuticals, Inc.