Roche and Gilead Sciences have launched a Phase III clinical trial in severe COVID-19 pneumonia, testing Roche’s Actemra/RoActemra with Gilead’s remdesivir. To date, remdesivir is the only drug shown to be effective against COVID-19 and is approved by the U.S. Food and Drug Administration (FDA) under emergency use authorization.
Actemra/RoActemra is an anti-IL-6 receptor biologic in both intravenous and subcutaneous formulations for adults with moderate-to-severe active rheumatoid arthritis (RA). It is also used to treat polyarticular juvenile idiopathic arthritis, giant cell arteritis and for chimeric antigen receptor CAR-T-cell-induced severe or life-threatening cytokine release syndrome (CRS).
In other words, Actemra/RoActemra is used to treat inflammatory diseases and to control the cytokine storms associated with certain immuno-oncology treatments. Gilead’s remdesivir is an antiviral drug. COVID-19 is marked by several unusual symptoms, including blood clotting, cytokine storms and severe pneumonia.
“As more information about COVID-19 pneumonia becomes available in these unprecedented times, it is more important than ever to work together to fight this disease,” said Levi Garraway, Roche’s chief medical officer and head of Global Product Development. “Based on our current understanding, we believe that combining an antiviral with an immune modulator could potentially be an effective approach to treating patients with severe disease. We’re pleased to partner with Gilead to determine whether combining these medicines could potentially help more patients during this pandemic.”
The REMDACTA Phase III trial is expected to begin enrolling in June and involve 450 patients worldwide.
Roche is also almost done with enrollment of another Phase III trial, COVACTA, studying intravenous Actemra/RoActemra alone with standard of care (SOC) compared to placebo plus SOC in hospitalized adults with severe COVID-19 pneumonia. The original design called for 330 patients but was expanded to allow for more robust data. The first patient was randomized on April 3, with about 450 patients enrolled. The company expects to share data from the COVACTA trial sometime this summer. The protocol for COVACTA allows patients who were treated with antiviral drugs, including experimental antivirals, so data from that subgroup can be used to supplement the COVACT study.
COVACTA is being run in partnership with the FDA and the Biomedical Advanced Research and Development Authority (BARDA). Roche is also taking part in the Accelerated COVID-19 Therapeutic Interventions and Vaccines (ACTIV) partnership led by the National Institutes of Health (NIH) and the Foundation of the NIH.
As mentioned above, in a study conducted by the U.S. National Institute of Allergy & Infectious Diseases (NIAID) of remdesivir in 1,063 COVID-19 patients, the drug showed on April 30 that patients recovered from the disease faster than patients who received placebo. This prompted the emergency use authorization by the FDA within days. What it showed was patients had a 31% faster time to recovery than the placebo group, from a median 15 days to a median 11 days.
The detailed data was published yesterday in The New England Journal of Medicine. Additional data suggested remdesivir was a little bit better in decreasing deaths than were originally reported, although the difference wasn’t statistically significant. Previously, death rates were 8% with the drug compared to 11.6% in the placebo groups. With additional two-week data, the rate for remdesivir was 7.1% compared to 11.9% for the placebo.
In a note to clients written on Saturday, May 23, Geoffrey Porges, analyst with SVB Leerink, said the numeric mortality improvement, if further validated, “can change sentiment” about COVID-19. In addition, the improvement can take some of the stress off hospital systems.
The drug didn’t seem to provide much help to COVID-19 patients with mild or moderate disease and patients on invasive ventilation or extracorporeal membrane oxygenation were almost identical in both arms of the trial. The likelihood in improvement in clinical status was 50% higher in patients receiving remdesivir than in the placebo cohort.
Porges wrote, “It is likely that the treatment benefit from remdesivir will increase in the real world once the lessons of this trial and other studies are incorporated into routine treatment practices.”
Umer Raffat, an analyst with Evercore noted of the published study data, “The single most important data disclosure that I was awaiting was this: How does mortality look different in patients that take remdesivir early? These early trials on COVID are all about identifying not only whether a drug works, but also when to initiate the drug.”
Information source: here