Ebola therapeutics trial terminated early
The US National Institutes of Health (NIH) announced Monday that an independent data and safety monitoring board (DSMB) has recommended that the PALM trial of four investigational agents to treat patients infected with Ebola be stopped early, and that all future patients be randomised to receive either Regeneron Pharmaceuticals' REGN-EB3 or Ridgeback Biotherapeutics' mAb114. In addition to these two Ebola therapy candidates, the PALM trial, which was conducted in the Democratic Republic of Congo, where the current outbreak is ongoing, was also investigating Mapp Biopharmaceuticals' ZMapp and Gilead Sciences' remdesivir.
The study, which as of August 9 had enrolled 681 patients out of target of 725, was initiated last November to test mAb114 and remdesivir against ZMapp as a control, due to it being considered the standard-of-care based on results from the previous PREVAIL II study. The PALM trial was later amended to include REGN-EB3 as a fourth treatment arm based on a recommendation from the World Health Organization. The primary endpoint was to compare mortality in patients with Ebola who received REGN-EB3, mAb114 or remdesivir to those treated with ZMapp.
According to the NIH, the DSMB recommendation was based on a preliminary analysis of 499 study participants which showed that patients administered REGN-EB3 or mAb114 "had a greater chance of survival" compared with the other two arms. Going forward, REGN-EB3 and mAb114 will be the two investigational treatments given as part of the study's extension phase to further evaluate safety until final results are known, after which an expanded access phase will be initiated using the lead therapeutics from the trial.
The NIH said a final analysis of the study results will be conducted after all data are generated and collected, which is expected to occur in late September or early October, with the findings to be submitted for publication in a peer-reviewed journal.
REGN-EB3, which was discovered using Regeneron's VelociSuite technologies and is being developed in partnership with the US Biomedical Advanced Research and Development Authority, "is a three-antibody cocktail designed with the goal of enhancing efficacy, reducing the development of viral sequences that lead to resistance, and increasing potential utility in future outbreaks as viruses continually evolve," said Christos Kyratsous, president of research, infectious diseases and viral vector technologies at the company.
Meanwhile, Ridgeback Biotherapeutics announced late last year that it licensed
mAb114 from the NIH, which initially developed the therapy. Commenting on the latest PALM trial news, the company said it "is focused on completing the advanced development of mAb114, including supporting the work necessary for FDA licensure and ensure an adequate supply of mAb114 is available to support treatment during the current and future Ebola outbreaks."
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