Roche’s arthritis drug Actemra already has backing from Chinese authorities to tackle COVID-19. But the Swiss drugmaker wants to confirm the use through careful examinations rather than relying purely on encouraging anecdotal stories.
The company’s now working with the FDA to start a randomized, double-blind, placebo-controlled phase 3 clinical trial to study Actemra in hospitalized patients with severe COVID-19 pneumonia caused by the novel coronavirus, it said Thursday.
Roche and its partner, U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority, plan to officially begin enrolling patients in early April in different parts of the world, including the U.S.
The study, coded Covacta, will pit Actemra against placebo, both on top of standard of care, in 330 patients. Investigators will evaluate patients’ clinical status, mortality, mechanical ventilation use and intensive care unit variables to determine the drug’s efficacy. Patients will be followed for 60 days, and an interim analysis will look for early signs of effectiveness.
For now, the company “cannot speculate on timing as that will depend on enrollment rates, but we will do what we can to share results as early as possible,” a Roche spokesperson told FiercePharma.
The decision comes after China’s National Health Commission added Actemra to its updated COVID-19 treatment guidelines in early March after Chinese physicians on the front line reported positive outcomes from its use to control dangerous lung inflammation in serious and critically ill patients.
That endorsement apparently triggered wide interest in the drug's potential in COVID-19. “We have received inquiries from government entities in many countries about the availability of Actemra for the treatment of patients with severe COVID-19 pneumonia,” the Roche spokesperson said. “Currently, we are in discussions with relevant authorities around the world to determine potential paths forward to provide Actemra to patients in this setting on an emergency basis, and will provide continued updates on our efforts.”
Actemra works by inhibiting the receptor of proinflammatory cytokine interleukin 6 (IL-6). It was first approved in the U.S. to treat rheumatoid arthritis, and in 2017 added to its label cytokine release syndrome (CRS)—a potentially fatal overreaction of the body’s immune system—in patients who received CAR-T cancer therapy.
In some COVID-19 patients, a key hallmark of disease worsening is also CRS, or in its more severe form known as cytokine storm. Chinese scientists from Tongji Hospital and the First Affiliated Hospital of the University of Science and Technology of China (USTC) have reportedly pinpointed IL-6 as responsible for the acute inflammatory disorder.
Several clinical trials testing Actemra in COVID-19 are already underway in China. USTC researchers are running a study comparing the Roche drug with conventional therapy in 188 patients. Another team at Peking University First Hospital is adding Fujifilm’s flu drug Avigan (favipiravir) on top of Actemra.
During a coronavirus press briefing on Tuesday, an official at China’s Science and Technology Ministry said Avigan is “clearly effective” in COVID-19 treatment. Physicians in Shenzhen, China, found patients taking Avigan turned negative in coronavirus RNA test after a median four days, compared to 11 days in the control group, the official said. The agency has officially recommended the med to health authorities for consideration in its COVID-19 treatment guidelines.
Favipiravir is approved in Japan and China, but not in the U.S.
Despite those existing China studies and anecdotal success stories from doctors, Roche argues the new Covacta study is important “because there are no well-controlled studies and limited published evidence” supporting Actemra’s use in COVID-19.
Meanwhile, Sanofi and Regeneron have also said they’re launching a clinical trial to study their FDA-approved IL-6 receptor inhibitor Kevzara for patients hospitalized with severe COVID-19. The two-part U.S. study will also test Kevzara as an add-on to best supportive care.
Editor's Note: The story has been updated with additional comments from Roche.