Preliminary results from the phase 2 portion of an ongoing phase 2/3 trial evaluating sarilumab (Kevzara; Regeneron and Sanofi) in hospitalized patients with coronavirus disease 2019 (COVID-19) showed that the interleukin-6 (IL-6) antagonist lowered C-reactive protein compared with placebo, meeting the primary end point of the study.
The phase 2 portion included 457 patients who were categorized as having either severe illness (requiring oxygen supplementation without mechanical or high-flow oxygenation), critical illness (requiring mechanical ventilation or high-flow oxygenation or requiring treatment in an intensive care unit), or multisystem organ dysfunction. Patients were randomized to receive intravenous sarilumab 200mg or 400mg or placebo. Across all treatment arms, baseline levels of IL-6 were elevated, with higher levels noted in critical patients compared with severe patients.
Results showed that treatment with both sarilumab 200mg (n=136) and 400mg (n=145) was associated with a greater change from baseline in C-reactive protein, a key marker of inflammation, compared with placebo (-77% and -79% vs -21%, respectively). As for clinical outcomes, the analysis did not show a significant benefit when the severe and critical groups were combined vs placebo. However, given the trend toward positive outcomes in the critical group, the Independent Data Monitoring Committee recommended that the ongoing phase 3 trial only enroll critical patients.
In addition, the phase 3 trial, which currently includes more than 600 patients in the critical group, will be amended to discontinue administration of the lower dose of sarilumab; all new patients will now receive the 400mg dose or placebo. Results from the trial are expected to be reported by June 2020.
Sarilumab is currently marketed under the brand name Kevzara for the treatment of moderately to severely active rheumatoid arthritis in adults who have had an inadequate response or intolerance to 1 or more disease-modifying antirheumatic drugs.