How do Ebola treatments like Inmazeb and Ebanga work, and what did the PALM trial show?
In 2018 a trial in an active conflict zone showed that two antibody drugs cut Ebola deaths, one of them from the blood of a survivor.
Ebola treatments called Inmazeb and Ebanga work by giving the body ready-made antibodies that latch onto a protein on the surface of the virus, so that it cannot get into cells. They were the winners of a trial in the middle of a conflict zone, the PALM trial, which began in the Democratic Republic of the Congo in November 2018.
Until then treatment was primarily supportive in nature: early supportive care with rehydration and symptomatic treatment improves survival. PALM, Pamoja Tulinde Maisha, meaning "Together Save Lives", was a trial at multiple treatment units testing four options: mAb114, REGN-EB3, and ZMapp. Despite the difficulty of running a clinical trial in a conflict zone, investigators enrolled 681 patients towards their goal of 725.
An interim analysis of the first 499 patients found mAb114 and REGN-EB3 superior to ZMapp. Overall mortality was 49 percent with ZMapp and 53 percent with , compared with 34 percent for mAb114 and 29 percent for REGN-EB3. Among those who arrived early after symptoms appeared, survival was 89 percent for mAb114 and 94 percent for REGN-EB3. The monitoring board halted the study, and the remdesivir and ZMapp arms were dropped.
PALM interim analysis: mortality by treatment
| Mortality | |
|---|---|
| ZMapp | 49% |
| Remdesivir | 53% |
| mAb114 (Ebanga) | 34% |
| REGN-EB3 (Inmazeb) | 29% |
The two winners became approved drugs. REGN-EB3 became Inmazeb, a combination of three antibodies, approved by the FDA for Zaire ebolavirus in October 2020. mAb114 became ansuvimab, or Ebanga, a single antibody, approved in December 2020. Its story starts with a person: ansuvimab was isolated from the blood of a survivor of the 1995 Kikwit outbreak, roughly ten years later. Both are aimed at Zaire ebolavirus, and ansuvimab has no documented efficacy against other ebolaviruses like Sudan virus.
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Recap
Antibodies that block the virus's surface protein cut mortality in the PALM trial to 34 percent and 29 percent, against 49 percent for ZMapp, but they were developed for Zaire ebolavirus.
💡 A trick to remember it · A survivor lends a key, a lab copies it, and the key fits one lock best: Zaire.
Surprising fact · Ebanga came from a survivor of a 1995 outbreak, whose blood was used about ten years later to isolate the antibody.
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No source, no claim. Every fact in this lesson (14 claims) cites at least one of these.