July 2, 2020
Regeneron and Sanofi have announced that a Regeneron-led phase 3 U.S. trial of Kevzara (sarilumab) in patients with COVID-19 failed to meet its primary or key secondary endpoints and has been stopped early.
The adaptive-design trial was enrolling patients with severe or critical COVID-19. The primary endpoint was a ≥1-point improvement on a 7-point ordinal scale in critical patients who were receiving mechanical ventilation at baseline; 194 patients were evaluable for the primary analysis. Patients had received Kevzara 400mg or placebo in addition to standard of care (SOC).
The interim results showed minor positive trends with Kevzara in the primary analysis group, but statistical significance was not achieved and the positive trends were outweighed by negative trends in a subgroup of critical patients who were not receiving mechanical ventilation at baseline.
Based on these outcomes, the trial has been stopped, including a partially enrolled, higher dose cohort (800mg). Detailed results will be submitted to a peer-reviewed journal for publication later in the year.
A separate Sanofi-led trial outside of the U.S. evaluating a different Kevzara regimen in patients with severe or critical disease is ongoing. The same Independent Data Monitoring Committee is overseeing both trials and has recommended continuation of the ex-U.S. trial. Results are expected in Q3 2020.
The failure of Kevzara, and for the most part, Actemra, to make a clinically meaningful impact on COVID-19 patients experiencing severe respiratory distress suggests that the immune hyperactivation frequently cited as the primary cause of serious complications associated with this virus is very different from the cytokine release syndrome induced by CAR T cell therapy.
The different immune response, or hyperactivation, profile associated with COVID-19 further highlights the many unknowns of the novel coronavirus. For Sanofi and Regeneron, provided there is no drastic turnaround in the ex-U.S. trial, the negative outcome for COVID-19 will accelerate the restructuring of their agreement for Kevzara that was placed on temporary hold due to these trials. We can assume that the sole global rights to Kevzara will now be transferred to Sanofi, as originally agreed at the end of 2019.
Source: Regeneron Press Release