In a world where clinical trials are often stopped due to patient deaths, safety issues or because the drug is likely to fail, an Ebola study in central Africa is ending early for the opposite reason. Investigators stopped a study testing experimental Ebola treatments from Gilead Sciences, Regeneron and the National Institutes of Health because the latter two drugs beat ZMapp, another unapproved drug that had been used in previous outbreaks.
The PALM study kicked off in November 2018 as part of the emergency response to an Ebola outbreak in Congo. Although MappBio’s ZMapp is not yet approved, the PALM study considered it the standard of care and used it as a control arm based on its use in a 2015 study pitting it against the standard of care at the time that included blood flow monitoring, giving intravenous fluids and concomitant drugs.
As of last Friday, the study had enrolled 681 patients of its target 725. But preliminary data showed patients treated with the NIH-developed mAb114 or Regeneron’s REGN-EB3 were more likely to survive compared to those treated with ZMapp or Gilead’s remdesivir, prompting an independent review board to recommend ending the study early. ZMapp and remdesivir will be discontinued in the study; patients who had been treated with those drugs may now opt into mAb114 or REGN-EB3 with their doctor’s input. All future patients will be randomized to receive Regeneron’s drug or the NIH-developed mAb114.
REGN-EB3 is a three-antibody cocktail designed to tamp down the development of mutations in Ebola that lead to drug resistance, while mAb114 is a monoclonal antibody based on an antibody found in the blood of a patient who had survived an earlier Ebola epidemic in Congo. The NIH’s National Institute of Allergy and Infectious Diseases (NIAID) licensed the treatment to Miami-based Ridgeback Biotherapeutics last December.
“While the final analysis of the data can occur only after all the data are generated and collected (likely late September/early October 2019), the [data and safety monitoring board] and the study leadership felt the preliminary analysis of the existing data was compelling enough to recommend and implement these changes in the trial immediately,” the NIH said in a statement Monday.
Sponsored by the NIAID and the national medical research organization of Congo, the study initially only included ZMapp, mAb114 and remdesivir, adding REGN-EB3 after a recommendation from the World Health Organization.
"This trial was conducted in difficult circumstances during a public health emergency, and we appreciate the efforts of the WHO and other experts to add REGN-EB3 to the trial," said Sumathi Sivapalasingam, M.D., senior director of early clinical development and experimental sciences at Regeneron, in a statement. "This trial is a remarkable advance in the decades-long struggle to respond to Ebola and we appreciate the tremendous efforts of the many governmental and non-governmental organizations who made it possible."