Contract Pharma Staff04.27.20
Regeneron and Sanofi released preliminary results from the Phase II portion of an ongoing Phase II/III trial evaluating Kevzara (sarilumab), an interleukin-6 (IL-6) receptor antibody, in hospitalized patients with severe and critical respiratory illness caused by COVID-19. Following a review by the Independent Data Monitoring Committee (IDMC) of all available data, the trial will be amended so that only critical patients continue to be enrolled to receive Kevzara 400 mg or placebo.
Preliminary analysis demonstrate 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.
The randomized Phase II 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 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.
In the preliminary Phase II 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. 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.
Last month, Regeneron and Sanofi moved rapidly to evaluate Kevzara in a randomized, placebo-controlled adaptively-designed U.S. Phase II/III trial in collaboration with U.S. groups including the Biomedical Advanced Research and Development Authority (BARDA).
Preliminary analysis demonstrate 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.
The randomized Phase II 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 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.
In the preliminary Phase II 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. 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.
Last month, Regeneron and Sanofi moved rapidly to evaluate Kevzara in a randomized, placebo-controlled adaptively-designed U.S. Phase II/III trial in collaboration with U.S. groups including the Biomedical Advanced Research and Development Authority (BARDA).
