- The World Health Organization has recommended the use of two arthritis drugs — Roche's Actemra as well as Sanofi and Regeneron's Kevzara — for patients with severe or critical COVID-19.
- The decision was announced alongside a meta-analysis of 27 clinical trials that tested the two drugs in nearly 11,000 patients. According to that analysis, treatment with either Actemra or Kevzara on top of standard drugs lowered rates of death from any cause after 28 days or progression to mechanical ventilation.
- The WHO's decision is only the second positive recommendation the organization has issued for a COVID-19 drug, following one in September for corticosteroids. It's the latest development in a perplexing research saga for so-called IL-6 inhibitors, which produced mixed results in multiple drugmaker trials before two U.K. studies showed their benefit.
The WHO's decision to classify IL-6 inhibitors as critical COVID-19 treatments would have been unthinkable as recently as December.
At the start of 2021, researchers and drugmakers had spent months running one study after another in search of evidence that Actemra and Kevzara could help severely ill COVID-19 patients. The drugs had been rushed into testing amid surging COVID-19 hospitalizations last spring and a hypothesis that they might help tame the overactive immune response associated with advanced stages of the disease.
But promising results from small studies in China and France, which suggested Actemra seemed to keep patients alive and off breathing support, proved hard to replicate. Actemra failed a large Phase 3 study called COVACTA. Sanofi and Regeneron then reported negative results with Kevzara and ended research of their drug in the disease altogether.
Other clinical tests kept proceeding, however, and more promising data trickled out. In September, Roche reported Actemra appeared to keep COVID-19 patients with pneumonia from needing invasive breathing support, even though it didn't extend their lives. Those results were reinforced by findings from two major academic studies in the U.K., known as REMAP-CAP and RECOVERY.
In REMAP-CAP, both Actemra and Kevzara improved outcomes for COVID-19 patients. In RECOVERY, a massive trial testing a variety of antivirals, antibodies and other COVID-19 drugs, Actemra cut the risk of death. Patients were also discharged from the hospital faster and shown to be less likely to need mechanical ventilation.
Those findings were enough to convince the Food and Drug Administration to grant Actemra an emergency clearance in June. But FDA support isn't a guarantee of similar backing from the WHO. The organization broke from U.S. regulators, for example, by deciding in November not to recommend Gilead's Veklury despite an authorization from the FDA.
In support of its decision, the WHO conducted an analysis of 27 trials and published its findings in the Journal of the American Medical Association on Tuesday. That analysis found patients on either Actemra or Kevzara and corticosteroids had a 21% risk of death within 28 days, versus a 25% risk for those on standard drugs alone. That means four lives would be saved for every 100 patients treated, the WHO said.
Additionally, patients who received an IL-6 drug and steroids had a 26% risk of needing invasive breathing support or death, compared to 33% for the placebo group. Though there were also more bacterial infections in IL-6-treated patients than those who received placebo, the WHO said the benefits observed "for the two most important patient outcomes warranted a strong recommendation."
Though there was more evidence in support of Actemra, tests of Sanofi and Regeneron's drug were generally done earlier, before steroids became the standard of care for hospitalized COVID-19 patients. The results were closer when comparisons were made among groups who had each received steroids, the WHO said.
The WHO did, however, acknowledge concern that its support may "exacerbate health inequities," as vaccines and antibody drugs are already far easier to access in wealthier countries. The humanitarian group Doctors Without Borders called on Roche to cut Actemra's price and share the know-how and technology needed to make the medicine to "ensure adequate supply and access for people everywhere."
Roche's main Actemra patent expired in 2017, but several secondary patents remain in low- and middle-income countries, preventing low-cost competition. The drug costs anywhere from $410 per 600 mg dose in Australia to $3,625 in the U.S., according to the nonprofit group.
"Manufacturers based in low- and middle-income countries urgently need to register and scale up production to increase the global supply," said Leena Menghaney, global IP advisor for Doctors Without Borders' Access Campaign, in a statement. "With more than 3.9 million lives already lost to COVID-19, the world cannot wait any longer for access to treatments that can help in increasing the chances of survival."