Yet another attempt at repurposing existing drugs for COVID-19 has fallen short.
Roche’s arthritis med Actemra failed to beat placebo at significantly improving clinical status among patients with severe COVID-19-related pneumonia in a phase 3 study, the Swiss pharma said Wednesday.
On the Covacta trial’s key secondary endpoint of death prevention by week four, a 19.7% death rate among Actemra patients didn't differ from the placebo group’s 19.4%.
This marks the second major blow to the theory of targeting inflammatory molecule IL-6 in treating COVID-19. Earlier this month, Sanofi and Regeneron pulled the plug on a phase 3 trial of their rival IL-6 inhibitor Kevzara after finding the drug couldn’t help severely ill COVID-19 patients who were on mechanical ventilation.
Roche rolled Actemra into the Covacta study in March after China included it in its COVID-19 treatment guidelines. Scientists there had noticed increased IL-6 levels in severe coronavirus cases and promising preliminary results with Actemra use in a small group of patients. Sanofi and Regeneron started the Kevzara trial around the same time.
The theory is that inhibiting IL-6 could help control a dangerous immune overreaction known as cytokine storm, which can cause lethal damage to the lungs. Actemra is approved to dampen the same phenomenon in blood cancer patients receiving CAR-T therapies.
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But in June, a study authorized by Italy’s drug authorities found Actemra didn’t improve severe respiratory symptoms, reduce ICU visits or cut mortality rates any better than standard of care in patients with early-stage COVID-19 pneumonia. At that time, hope was still alive that the med might prove useful for more advanced disease.
That belief pushed up sales of the decade-old rheumatoid arthritis med, originally developed by Roche’s Japanese subsidiary Chugai, by 40% year over year to CHF 795 million ($868 million) in the second quarter. Jefferies analyst Naoya Miura previously predicted a COVID-19 indication could add JPY 37 billion ($350 million) to Actemra's annual sales.
There were some positive signs in favor of Actemra in the Covacta trial. For example, Actemra patients were slightly more likely to show clinical improvement at week four, and the median time to hospital discharge or “ready to discharge” for Actemra was better at 20 days, compared with 28 days for placebo. However, these benefits were not considered statistically significant.
Roche said it will publish detailed results in a peer-reviewed journal. Besides Covacta, Roche is collaborating with Gilead Sciences on the phase 3 Remdacta trial, which aims to find out whether combining Actemra and the U.S. firm’s antiviral remdesivir works better than either drug alone. Remdesivir previously showed it could cut recovery time by 30% for hospitalized COVID-19 patients.
Meanwhile, other drugmakers are also repurposing existing drugs for COVID-19. Novartis is testing Incyte-partnered JAK inhibitor Jakafi and IL-1beta blocker Ilaris, AstraZeneca is evaluating BTK blood cancer med Calquence and diabetes drug Farxiga, Eli Lilly is contributing JAK inhibitor Olumiant for pairing with remdesivir and Alexion is investigating rare disease drug Ultomiris.