Regeneron and Sanofi’s trial of Kevzara (sarilumab) in hospitalised patients with severe or critical respiratory illness caused by COVID-19 is being amended to include a narrower subset of patients afters failing to show a benefit in a wider group.
Preliminary results from the Phase II portion of an ongoing Phase II/III trial evaluating the interleukin-6 (IL-6) receptor antibody will now only allow critical patients to be enrolled to receive Kevzara 400mg or placebo.
The move follows preliminary analysis of the Phase II portion of the trial, which showed 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.
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 II trial (n=126) were not reproduced in Phase III 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 II portion, around 80% were discharged, 10% of patients died and 10% remain hospitalised.
“Even in a pandemic setting, it’s both crucial and possible to obtain controlled data in adequately-sized trials to provide the evidence needed to inform optimal medical care,” said George Yancopoulos, Regeneron co-founder, president and chief scientific officer.
“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.
“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.”
28th April 2020