Kevzara Fails in Phase 3 COVID-19 Clinical Trial

Sanofi and Regeneron Pharmaceuticals recently announced that the US Phase 3 COVID-19 clinical trial of Kevzara in patients requiring mechanical ventilation did not meet its primary and key secondary endpoints compared to best supportive care alone.

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Minor positive trends were found in the primary pre-specified analysis group, or critical patients receiving Kevzara 400 mg who were ventilated at baseline. But the trends  did not reach statistical significance.

But these positive findings were countered by negative trends in the subgroup of critical patients who were not mechanically ventilated at baseline.

The primary analysis group included 194 patients who were critically ill with COVID-19 and receiving mechanical ventilation at the time of enrollment. The primary endpoint assessed the percentage of patients who achieved at least a 1-point change from baseline on a 7-point scale, Sanofi said.

In the primary analysis group, 80 percent of Kevzara patients experienced adverse events and 77 percent of placebo patients experienced the same.

Serious adverse events that occurred in at least 3 percent of patients included multi organ dysfunction syndrome (6 percent Kevzara and 5 percent placebo) and hypotension (4 percent Kevzara and 3 percent placebo).

Sanofi stated that based on the results, the trial has been stopped, which includes a second cohort of patients who received a higher dose of Kevzara (800 mg).

Detailed results will be submitted to a peer-reviewed publication later this year.

A separate Sanofi-led trial outside of the US in hospitalized patients with severe and critical COVID-19 using a different dosing regimen is ongoing, Sanofi noted.

The same Independent Data Monitoring Committee (IDMC) is overseeing both the Regeneron-led US trial and the Sanofi-led trial outside of the US. The committee has recommended that the trial outside of the US continue.

The companies expect to report results in the third quarter of 2020.

Kevzara is a fully human monoclonal antibody that binds to the IL-6 receptor on normal cells. Experts believe the drug may improve patients with COVID-19 who are more susceptible to life-threatening respiratory failure by decreasing the inflammatory response. 

FDA first approved Kevzara in 2017 for the treatment of adult patients with active rheumatoid arthritis. Kevzara was originally developed under collaboration between Regeneron and Sanofi, with Regeneron leading the US-based trials and Sanofi leading international trials. 

At the end of March, HHS announced support for the Phase 2/3 clinical trial to evaluate Kevzara for severely ill COVID-19 patients.

The Biomedical Advanced Research and Development Authority (BARDA) alsosupported the clinical trial.

The Phase 2/3 clinical trial intended to focus on the safety and effectiveness of Kevzara in decreasing the time that a person with COVID-19 remains ill. The first part of the trial evaluated the effectiveness of the drug on fever and patients’ need for supplemental oxygen.

Had the trial not been stopped, the second part of the trial would have evaluated the improvement in longer-term outcomes, including whether the drug reduces mortality or the need for mechanical ventilation, supplemental oxygen, and hospitalization. 

The scale consisted of seven different factors, including:

• Hospitalization, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation
• Hospitalization, requiring non-invasive ventilation or high flow oxygen devices
• Hospitalization, requiring supplemental oxygen
• Hospitalization, not requiring supplemental oxygen, but requiring ongoing medical care
• Hospitalization, not requiring supplemental oxygen and no longer requiring ongoing medical care
• Hospital discharge
• Death

Sanofi noted that a second cohort, which was partially recruited, compared Kevzara 800 mg versus placebo.