Researchers will stop using Sanofi and Regeneron's arthritis drug Kevzara in patients hospitalized with COVID-19, but who didn't yet need mechanical ventilation, after study results suggested a greater percentage of those treated did worse than those who received a placebo.
The closely watched trial will continue in critically ill patients who require ventilation for respiratory support, the companies said Monday, in hopes Kevzara could still prove beneficial. In that group, interim study results showed a smaller share of patients taking the drug died or remained on a ventilator after 29 days when compared to placebo-treated patients.
The trial analysis, conducted by an independent data monitoring panel, demonstrates the challenges facing other autoimmune disease drugs being repurposed to treat people severely ill with coronavirus infections. The strategy attempts to avert death and complications in those patients struggling to breathe because of an overactive immune response sometimes termed a "cytokine storm."
Roche's Actemra, which works similarly Kevzara, was the first such drug studied as a treatment for COVID-19, and other companies have advanced immune-modulating drugs like the cancer therapies Jakafi and Calquence into clinical testing.
Researchers using this approach will have to answer the question of whether trying to tamp down the cytokine storm won't also restrain the immune system so much that it can't fight off the novel coronavirus, called SARS-CoV-2. Actemra has been used successfully to suppress cytokine release syndrome in patients undergoing cancer cell therapies, but those patients are not simultaneously suffering from a viral infection.
The most closely tracked drug in the field, Gilead's remdesivir, attempts to combat the viral infection directly.
Participants in the two-part study of Kevzara had elevated levels of an immune-response protein called interleukin-6, or IL-6, which the drug targets. The trial actually met its primary endpoint for the first trial segment, showing treatment led to greater reductions in a related inflammatory biomarker called C-reactive protein when comparing Kevzara to placebo.
But data on clinical outcomes suggested Kevzara wasn't associated with any benefit in those patients who had not progressed to mechanical ventilation, which the companies called the "severe" group. These results were considered "exploratory," or preliminary.
In fact, the announcement from Sanofi and Regeneron noted "there were negative trends for most outcomes in the 'severe group,'" according to an analysis by the study's data monitoring committee. Those trends, which suggested Kevara might be hurting patients, were not confimed in the larger Phase 3 part of the trial, however.
The disappointing results will likely raise questions about whether Kevzara, and other treatments like it, will ultimately play a role against COVID-19. While there's hope a benefit in critical patients could eventually emerge, the multiple analyses, doses and groups may have resulted in a "spurious conclusion" that is "not indicative of any real benefit conferred by Kevzara," wrote RBC Capital Markets Kennen MacKay in a note to clients.
But the results could prove a clear example of the value of placebo-controlled studies during a fast-spreading and overwhelming disease outbreak.
"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 Yancopoulos, Regeneron's chief scientific officer, in a statement.
Sanofi and Regeneron's announcement contrasts with another disclosure Monday from a French trial of Actemra, which also targets IL-6. That study, in patients not needing intensive care at hospital admission, showed that fewer patients treated with the Roche drug died or progressed to ventilation than patients given a placebo — a finding seemingly at odds with the data from Sanofi and Regeneron.
Few details were released from that French study, however, and the statement indicated their finding would need to be confirmed by additional trials.
Interest in IL-6 blockers was spurred by an early Chinese study that showed use of Actemra reduced fever and need for ventilation in COVID-19 patients. That study had no comparative placebo arm, however.