Global health officials today announced a pause in the clinical trial of four investigational Ebola drugs in the Democratic Republic of Congo (DRC) outbreak region after an early look at the data found that two of the drugs—Regeneron and mAb 114—stood out as more effective.
In other outbreak developments, the DRC reported 38 more cases since Aug 9, lifting the outbreak total past 2,800 to 2,831.
Promising Regeneron findings triggered pause
An independent monitoring board meets periodically to review safety and efficacy data, and at their Aug 9 review recommended that the study be stopped and all future patients be randomized to receive either Regeneron, an antibody cocktail, or mAB 114, an antibody treatment developed from a human survivor of the virus. The other two drugs involved in the original trial were zMapp, which in an earlier trial didn't show statistically significant efficacy but performed better than standard care alone, and Remdesivir, an antiviral drug.
Earlier in the outbreak, an ethics committee in the DRC approved the four experimental treatments for compassionate use, and patients at all of the country's Ebola treatment centers have had access to them, along with safety monitoring. However, the formal clinical trial has been under way since November at four treatment centers with the help of the Alliance for International Medical Action (ALIMA), the International Medical Corps (IMC), and Doctors Without Borders (MSF).
At a media telebriefing today, Anthony Fauci, MD, director of the National institute of Allergy and Infectious Diseases (NIAID), said Regeneron was the drug that crossed the efficacy threshold, triggering a pause in the study. And he said the group recommended proceeding with mAb 114, because there were only small differences in the data between the two drugs.
He said the findings of the study are a "ringing endorsement" that ethical and scientifically sound research can be conducted in an outbreak setting.
Jean Jacques Meyumbe Tamfum, PhD, an Ebola expert who was recently appointed to head a group that is now leading the DRC's Ebola response, said he was grateful for the support of international partners, who are working in an extremely difficult setting. "We can no longer say that Ebola virus disease is not curable."
Early data details
As of Aug 9, the trial had enrolled 681 patients toward a total of 725. Fauci said mortality for Regeneron was 29% and 34% for mAb 114. However, mortality was somewhat higher for zMapp (49%) and Remdesivir (53%). He said results were even more impressive in patients who had low viral loads: 6% for Regeneron, 11% for mAb 114, 24% for zMapp, and 33% for Remdesivir.
Fauci cautioned that the data are preliminary. He said the numbers could change, but that two of the drugs are clearly better. He estimated that about 15% of the study participants had been vaccinated and that about 59% of them were found to have a low viral load.
Supplies of both mAb 114 and Regeneron are adequate for continuing to treat people in Ebola treatment centers and to keep the extension part of the trial going, he said. There are 300 doses of mAb 114 on hand, with more doses coming from a second production lot in early September and a second production lot with more doses in late 2019. For Regeneron there are several hundred treatment courses, and the company is committed to an uninterrupted supply.
The study was sponsored by the Institut National de Recherche Biomedicale (INRB) in the Democratic Republic of Congo and the NIAID, part of the US National Institutes of Health (NIH).
Implications for outbreak management
Mike Ryan, MD, the WHO's executive director of emergency programs, told reporters that the WHO welcomes the results and he praised all of the Ebola workers, including the ones working on the infrastructure that allows doctors and nurses to deliver the treatments.
However, he said the tragedy is that not enough people are being treated and not enough people are coming to the hospital. "There are outstanding results for people who seek care early."
Ryan added, "Having effective drugs is fantastic news, but if we don't get to use them, that's a problem." A persistent problem in the DRC's outbreak is that sick people are staying in the community too long, often as long as 5 to 6 days after symptom onset, which reduces their chances for successful treatment and exposes others to the virus, he said.
It's vital to get the promising treatment findings out to communities as clearly as possible. All patients will have access to the drugs, whether their center was involved with the trial or not, Ryan said.
Latest outbreak numbers
In updates to the WHO's Ebola dashboard, the DRC reported 8 more cases on Aug 10, 15 more on Aug 11, and 15 more cases today, putting the overall total at 2,831.
Health officials are still investigating 326 suspected infections.
Since Aug 9, 21 more people died from the disease, lifting the fatality count to 1,888.
Aug 12 WHO press release
Aug 12 NIAID press release
WHO online Ebola dashboard