- Two experimental Ebola treatments, including a drug from Regeneron, are advancing to the next stage of a large clinical trial after an independent committee determined they offer significantly better survival rates than the standard of care.
- The trial enrolled nearly 700 patients across four Ebola Treatment Centers in the Democratic Republic of the Congo, where the second deadliest outbreak on record has raged for more than a year. The World Health Organization reports that nearly 1,800 people with confirmed cases of Ebola have died from this outbreak.
- Regeneron's drug, REGN-EB3, and another antibody-based therapy called mAb114 will now be evaluated in an extension phase of the trial, which investigators stopped early because of preliminary findings from 499 participants. Researchers expect to conduct a final analysis of the trial once they finish collecting data in September or October.
Since 2017, the DRC has experienced three Ebola outbreaks. The first involved eight cases, half of which were fatal, while a larger one that began and ended in 2018 recorded 54 cases and a fatality rate of 63%.
The latest outbreak is barely a year old, but is already the deadliest and most widespread for the central African country. WHO reports that, over the 21-day period from July 17 to Aug. 6, there were 257 confirmed cases of the disease across the DRC's two most affected provinces. To date, nearly 2,700 people have been infected in the outbreak.
Preliminary findings from the PALM study come as health officials try to contain the surge.
In the trial, 29% of patients given REGN-EB3 died, as did 34% of those treated with mAb114, according to data cited by STAT. By contrast, results show a 49% mortality rate in a comparator arm of patients who received ZMapp, an experimental Ebola treatment considered the current standard of care.
Another study arm tested Gilead's antiviral drug remdesivir, but a mortality rate of 53% means it won't advance to the extension phase of the trial.
Sumathi Sivapalasingam, senior director of early clinical development and experimental sciences at Regeneron, said the extension phase will focus on overall safety and won't contribute to the study's efficacy endpoint.
Going forward, any patient in the remdesivir or ZMapp arms will be allowed to undergo randomization into either the REGN-EB3 or mAb114 arm.
Regeneron just learned of the PALM data from the National Institutes of Health, according to Sivapalasingam, and still needs to consult with the Biomedical Advanced Research and Development Authority and the Food and Drug Administration about a path to registration.
Sivapalasingam indicated that the unmet need in Ebola treatment is large enough to accommodate multiple new treatments, should both REGN-EB3 and mAb114 gain approval.
"For a rare, deadly disease, the more options we that we have, the better, because there are sometimes drug shortages," said Sivapalasingam. "So it really doesn't alter our plans for either registration or stockpiling."
The deadliest Ebola outbreak on record occurred just a few years ago. Spanning from 2014 to 2016, it is thought to have claimed 11,308 lives across Guinea, Liberia and Sierra Leone.
ZMapp was one of the experimental drugs used to treat patients during that outbreak. Researchers have since investigated the drug in a randomized clinical trial, but it ultimately missed on the main efficacy endpoint.
Still, Sivapalasingam notes that one of the obstacles Regeneron has encountered is getting doctors and regulators to take a chance on REGN-EB3.
"There was a little bit of a hesitation to start using REGN-EB3 under compassionate care, and so we worked very closely with our partners at WHO and Doctors Without Borders to get them comfortable using this in patients."