Sanofi and Regeneron Halt Phase 3 Trial of Kevzara (Sarilumab) for COVID-19 Due to Lack of Efficacy

Compiled by Fan Dongdong

On July 2 local time, Sanofi and Regeneron announced the results of the Phase 3 trial of Kevzara (sarilumab) for the treatment of COVID-19. The results showed that in severe COVID-19 patients requiring mechanical ventilation, Kevzara 400 mg combined with best supportive care did not meet the primary and secondary endpoints compared with best supportive care alone.

The primary analysis population of this trial included 194 patients with severe COVID-19 who were receiving mechanical ventilation at enrollment. The primary endpoint was assessed using a 7-point ordinal scale, calculating the percentage of patients who demonstrated an improvement of at least 1 point from baseline. The scale categories are: 1) death; 2) hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) hospitalized, requiring non-invasive ventilation or high-flow oxygen devices; 4) hospitalized, requiring supplemental oxygen; 5) hospitalized, not requiring supplemental oxygen but needing ongoing medical care; 6) hospitalized, not requiring supplemental oxygen and no longer needing ongoing medical care; 7) discharged from hospital. A second cohort enrolled 27 subjects to compare Kevzara (800 mg) with placebo.

In the trial, Kevzara showed a modest positive trend in the prespecified primary analysis population, but this did not reach statistical significance; among critically ill COVID-19 patients who did not require mechanical ventilation, these trends were “offset by negative trends.” In the primary analysis population, 80% of patients in the Kevzara group and 77% of patients in the placebo group experienced adverse events. Serious adverse events occurred in at least 3% of patients. Common adverse reactions in the Kevzara group included multiple organ dysfunction syndrome (6% in the Kevzara group vs. 5% in the placebo group) and hypotension (4% in the Kevzara group vs. 3% in the placebo group).

In April, the Phase II trial results for Kevzara at doses of 200 mg and 400 mg were also discouraging, showing no significant clinical benefit compared with placebo in patients hospitalized with severe COVID-19. At that time, the two companies stated that they would modify the study based on these results to continue enrolling critically ill patients to receive the 400-mg dose. However, with the emergence of further unfavorable trial results, the trial has now been discontinued, including the second cohort receiving Kevzara at an 800-mg dose.

Sanofi and Regeneron stated that the Kevzara trial was designed based on a small (n=21), single-arm study conducted in China, which found elevated IL-6 levels in hospitalized COVID-19 patients with high fever. The study suggested inhibiting this pathway using Roche’s anti-IL-6 receptor antibody Actemra, which is believed to rapidly reduce fever and improve oxygenation in severe cases. Two weeks ago, Actemra failed in a clinical trial involving patients with early-stage COVID-19, indicating that blocking this pathway may only offer some efficacy in the most severely ill patients.

In addition, Sanofi is leading a separate trial outside the United States in hospitalized patients with severe COVID-19, using a different dosing regimen.

Reference Source: Sanofi and Regeneron provide update on Kevzara® (sarilumab) Phase 3 U.S. trial in COVID-19 patients