Arthritis Drug Disappoints as a COVID-19 Treatment
On April 27, 2020, Regeneron Pharmaceuticals Inc. and Sanofi SA announced they will discontinue part of a clinical study exploring whether their arthritis therapy, Kevzara, could treat certain hospitalized COVID-19 patients.
These companies said in a press release this decision was made ‘because the Kevzara looked unlikely to help them the average COVID-19 disease patients.’
Following a review by the Independent Data Monitoring Committee of all available Phase 2 and Phase 3 data, the trial will be immediately amended so that only "critical" patients continue to be enrolled to receive Kevzara 400 mg or placebo.
It was hoped that the drug would help ease the immune system’s overreaction to the SARS-CoV-2 coronavirus, which is called a “cytokine storm” that causes inflammation and fluid buildup in the lungs of many of the sickest patients.
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 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 the 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.
"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 D. Yancopoulos, M.D., Ph.D., Regeneron Co-Founder, President, and Chief Scientific Officer, in a press release.
"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."
The companies are also conducting a second trial in countries outside of the U.S.
The Phase 3 trial of Kevzara in approximately 400 patients hospitalized with COVID-19 infection is currently enrolling in Italy, Spain, Germany, France, Canada, Russia, Israel, and Japan.
Initial results from this second trial are expected in the third quarter of 2020. The findings from the U.S. trial will be shared immediately with the IDMC and similar amendments to the trial outside the U.S. will be considered.
The U.S. Kevzara trial has been funded in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; and BARDA.
The use of Kevzara to treat the symptoms of COVID-19 is investigational and has not been fully evaluated by any regulatory authority.
Kevzara was jointly developed by Regeneron and Sanofi under a global collaboration agreement.
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