Virus World

A trial of four experimental Ebola treatments carried out in the Democratic Republic of the Congo (DRC) has been stopped early after two of them showed strong signs of being able to save patients’ lives. The preliminary results were reported this morning by Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, one of the partners in the study. The two treatments will now be made widely available and could help end the yearlong outbreak in the DRC, which has already killed more than 1800 people, scientists say.

The PALM trial (short for the Swahili expression pamoja tulinde maisha, which means “together save lives”) evaluated three Ebola antibody preparations and one antiviral drug in a randomized controlled trial conducted in the midst of the devastating outbreak, which has hit two provinces in the eastern DRC mired in violence. “Today, we have started a new chapter. From now on, we will no longer say that Ebola is not curable,” Jean-Jacques Muyembe-Tamfum, head of the DRC’s National Institute for Biomedical Research in Kinshasa, a partner in the trial, said at the press conference. “This advance will, in the future, help save thousands of lives.” (Muyembe, who was part of the team that discovered Ebola 43 years ago, took over command of the outbreak response in the DRC on 22 July.)

Still, the data on ZMapp were deemed good enough to use the drug as a control in future trials. In the PALM trial, three other trials were compared to ZMapp:

• The monoclonal antibody mAb114, which has its roots in the 1995 Ebola outbreak in Kikwit, DRC. During that episode, Muyembe attempted to treat patients with a mixture of antibodies from Ebola survivors. Years later, researchers at NIAID isolated antibodies from those survivors; mAb114, which is now being developed with Ridgeback Biotherapeutics in Miami, Florida, was the most promising one.
• REGN-EB3, a cocktail of three monoclonal antibodies developed by Regeneron Pharmaceuticals in Eastview, New York. The antibodies were generated by inoculating mice with “humanized” immune systems with the Ebola virus.
• The antiviral drug remdesivir, produced by Gilead Sciences in Foster City, California.

The trial started in November 2018 in four Ebola treatment units in the communities of Beni, Butembo, Katwa, and Mangina, with the aim of enrolling 725 patients. On 9 August, an independent data and safety monitoring board reviewed data for 499 patients and found that REGN-EB3 was much better than ZMapp. Overall, 49% of patients receiving ZMapp—and 53% of those who received remdesivir—died, compared with only 29% of those on REGN-EB3. That difference was big enough to meet the predetermined criterion for stopping the trial early. In the group that received mAb114, mortality was 34%, a rate deemed close enough to that of the Regeneron cocktail that its use should continue.  In the 41% of trial participants who sought treatment early after infection and had lower levels of Ebola virus in their blood, the two new treatments had astonishing success: Mortality plummeted to 6% in the Regeneron antibody group and to 11% with mAb114. (With ZMapp and remdesivir, mortality rates in people with low viral load were 24% and 33%, respectively.) There is far less hope for patients with a high viral load, however: Even with the best treatment, REGN-EB3, their death rate was 60%.