First Phase III data for an IL-6 mAb in COVID-19 disappoint
Kevzara from Sanofi and Regeneron misses key endpoints in study in severe COVID-19
A Phase III miss for IL-6 inhibitor Kevzara may not reflect a broader problem with the target or the strengthening theory that immune modulators are the best line of defense against severe forms of COVID-19. But the readout, which was in the most severe COVID-19 patients, is the latest evidence against the mAb from Sanofi and Regeneron in the pandemic.
A 400 mg dose of Kevzara sarilumab missed the primary and key secondary endpoints in a trial in critically ill COVID-19 patients on mechanical ventilation, Sanofi (Euronext:SAN; NASDAQ:SNY) and Regeneron Pharmaceuticals Inc. (NASDAQ:RGEN) announced late Thursday.
In 194 patients, Kevzara failed to increase the percentage of patients who achieved at least a one-point improvement on a seven-point ordinal scale, the primary endpoint, compared with best supportive care.
On the primary endpoint and secondary endpoints including the proportion of patients who died by day 29 and the proportion of patients who recovered by day 22, the companies said there were positive trends that didn’t reach statistical significance among patients mechanically ventilated at baseline. But those trends were countered by negative ones in critical patients who weren’t mechanically ventilated at baseline.
Early in the course of the pandemic, IL-6 inhibitors were identified as a promising mechanism for COVID-19 when a small Chinese study detected elevated levels of IL-6 in febrile hospitalized patients.
While Kevzara has disappointed -- failing a previous trial in severe patients -- another anti-IL-6 mAb, Actemra tocilizumab from the Genentech Inc. unit of Roche (SIX:ROG; OTCQX:RHHBY), has performed better in the most severe patients in earlier stage trials.
Both drugs go after the same target, but do differ. Sanofi has reported that Kevzara binds the IL-6 receptor with higher affinity than Actemra.
Actemra improved clinical outcomes in trials of moderate and severe COVID-19 patients and mechanically ventilated patients, but missed in a trial of moderate patients. Most of these trials were not randomized, placebo-controlled trials; however, Phase III trials are ongoing.
Those data, plus promising data from the U.K.’s RECOVERY master protocol trial on dexamethasone, have added support to the hypothesis that immune modulators may improve patient outcomes during later stages of disease when damaging inflammatory processes take hold (see “Clinical Scorecard for COVID-19”).
Data are expected next quarter from a separate Sanofi-led trial of Kevzara outside the U.S. in severe COVID-19 patients; the trial is using a different dosing regimen.
Kevzara and Actemra are approved to treat rheumatoid arthritis (RA).
IL-6 - Interleukin-6