When Sanofi and Regeneron’s Kevzara and Roche’s Actemra both flopped in trials in COVID-19 patients, it looked like the end of road for targeting IL-6 to control coronavirus-related pneumonia. But now, the Swiss pharma’s option has staged a comeback—sort of.
In the Empacta trial, Actemra used alongside standard of care reduced the risk of COVID-19 pneumonia patients advancing to mechanical ventilation or death by 44%, Roche said Friday.
Though the company said it will share the data with the FDA and other health authorities, the drug’s regulatory path remains unclear, to say the least, what with a lack of showing on the key marker of death rate—and that previous trial failure.
The phase 3 Empacta trial enrolled patients who needed supplemental oxygen but weren’t ill enough to require mechanical ventilation. About 85% of the 389 participants were from minority groups. By Day 28, only 12.2% of patients on Actemra had progressed to mechanical ventilation or death, compared with 19.3% of placebo patients.
However, Actemra failed to show benefits in several key secondary measures. Most notably, there was no statistically significant difference in death rate. In the placebo arm, 8.6% of patients died, while 10.4% of Actemra patients did.
The drug did appear to help patients leave the hospital more quickly, even though the difference in median days to discharge—six days for Actemra and 7.5 days for placebo—was not statistically significant.
That favorable trend also cropped up in the previous trial, dubbed Covacta. In that study, whose results were unveiled in late July, the median time to hospital discharge or “ready to discharge” was shorter for Actemra at 20 days, versus 28 days for placebo. But Actemra failed to top placebo in terms of clinical status improvement after four weeks—the trial's primary endpoint—even though the likelihood of clinical improvement was slightly higher for the Roche drug.
Similarly, in the current Empacta trial, it took Actemra a median of six days to help patients improve on the ordinal clinical status scale, while placebo patients saw improvements after seven days. The difference once again didn’t cross the statistical significance bar.
Actemra first kindled hope in the early days of the pandemic when Chinese physicians reported using it to manage dangerous immune system reactions in severe patients. Other than rheumatoid arthritis, the Roche drug is approved in the U.S. to treat a similar condition—cytokine release syndrome—in cancer patients treated with CAR-T immunotherapies.
But disappointing news followed. Sanofi and Regeneron first scaled back their study of rival drug Kevzara to only focus on critically ill patients who were already on ventilation, only to shut the whole endeavor down after seeing no benefits in Kevzara patients. And Roche’s Covacta flop only reinforced the impression that IL-6 inhibitors probably don’t work for COVID-19.
Now, the Empacta trial win offers a glimpse of hope for Roche. But against the backdrop of lifesaving benefits demonstrated by low-cost corticosteroids including dexamethasone, there might be little interest in a drug that doesn’t appear to cut the death rate.
Meanwhile, Roche is also pairing Actemra with Gilead Sciences’ antiviral Veklury, better known as remdesivir, in the phase 3 Remdacta trial. Eli Lilly’s JAK arthritis med Olumiant combined with Veklury helped patients recover faster in a recent trial run by the National Institute of Allergy and Infectious Diseases.