The question of whether seriously ill COVID-19 patients can benefit from anti-inflammatories like Roche’s Actemra and Sanofi and Regeneron’s Kevzara has dogged practitioners in the United States thanks to conflicting clinical trial results.
The United Kingdom, on the other hand, has reached a definitive answer on the two drugs, both of which are IL-6 inhibitors: They significantly reduce the risk of death in COVID-19 patients needing intensive care, and they should be used to ease the pressure hospitals are now facing as the coronavirus pandemic continues to intensify, the country’s National Institute for Health Research (NIHR) said Thursday.
The recommendation came after data from an NIHR-sponsored study showed that Actemra and Kevzara can cut hospital stays for COVID-19 patients admitted to intensive care by 10 days and can lower the risk of death by 24% in patients who receive either drug within a day of admission. That finding prompted the U.K. government to recommend to the National Health Service (NHS) that IL-6 inhibitors be rolled out for the treatment of COVID-19.
“We have worked quickly to ensure this treatment is available to NHS patients without delay,” the U.K.’s Health and Social Care Secretary Matt Hancock said in a statement, adding that the trial outcome marked a “landmark development in finding a way out of this pandemic.”
The trial data, which have not yet been peer-reviewed, were published (PDF) on the preprint site medRxiv.
Actemra and Kevzara may have been embraced in the U.K., but their path to success in COVID-19 in the U.S. is much less clear. An observational study published last fall in JAMA Internal Medicine reported that Actemra was linked to a 29% reduction in the risk of death in critically ill COVID-19 patients.
But a randomized clinical trial of Roche’s drug in Italy concluded that it produced no improvement in disease progression or death. A similar trial in France reported that Actemra’s effectiveness in moderate-to-severe COVID-19 patients was mixed at best.
As for Sanofi and Regeneron, they’ve also struggled to make a strong case for Kevzara in COVID-19. Over the summer, the companies shut down a trial of the drug after finding it wasn’t helping patients on ventilation. Then they released data from a study of Kevzara in several countries showing that the drug failed to produce statistically significant differences in length of hospital stays or symptom improvement.
The potential benefit of IL-6 inhibitors in coronavirus patients was recognized by scientists early on during the pandemic. When the immune system fights the virus, it often unleashes a flood of inflammatory molecules that can cause organ failure. Controlling IL-6 seemed like a straightforward way to control that reaction, so many experts remain puzzled as to why Actemra and Kevzara, both of which are approved to treat rheumatoid arthritis, have not consistently performed well in COVID-19 trials.
Roche continues to study Actemra in COVID-19, launching a clinical trial last summer of the drug in combination with Gilead’s Veklury (remdesivir). That study is ongoing and recruiting patients at 73 hospitals around the world.