Study finds Ebola treatment ZMapp holds promise, although results not definitive

Trial shows rigorous clinical research feasible during a public health emergency.

“Although we do not have definitive evidence that ZMapp is superior to the optimized standard of care, the results of the PREVAIL II trial are promising and provide valuable scientific data,” said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. “Importantly, the study establishes that it is feasible to conduct a randomized, controlled trial during a major public health emergency in a scientifically and ethically sound manner.”

ZMapp, developed by Mapp Biopharmaceutical, based in San Diego, is composed of three different laboratory-made proteins called monoclonal antibodies. The treatment is designed to prevent the progression of EVD within the body by targeting the main surface protein of the Ebola virus. Earlier studies in nonhuman primates demonstrated that ZMapp had strong antiviral activity and prevented death when administered as late as 5 days after experimental infection with Zaire ebolavirus.

The study launched through a collaboration between the Liberian Ministry of Health and NIAID, known as the Partnership for Research on Ebola Virus in Liberia (PREVAIL). It later expanded to include research partners within the countries of Sierra Leone and Guinea and the French medical research organization INSERM.

The trial enrolled 72 participants of any age with confirmed Ebola virus infection from March 2015 through November 2015. The participants came from Sierra Leone (54 patients), Guinea (12 patients), Liberia (five patients) and the US (one patient, a health care worker evacuated from Sierra Leone).

The average age of the participants was 24 years, and slightly more than half were women. Investigators closed the study in January 2016 because they could not enroll additional patients, up to the targeted 200, because of the decline in the number of new Ebola cases as the outbreak diminished.

The study sought to determine whether the experimental drug ZMapp plus the optimized standard of care for treating EVD — providing intravenous fluids, balancing electrolytes needed to maintain bodily functions, and maintaining healthy oxygen and blood pressure levels — was superior to the optimized standard of care alone in reducing deaths caused by EVD. All participants received the optimized standard of care, and half were randomly assigned to also receive three intravenous infusions of ZMapp administered 3 days apart.

Investigators compared the number of deaths in each group at 28 days after enrollment. Thirteen deaths (37% mortality) were reported in the group of 35 patients who received the optimized standard of care only, while eight deaths (22% mortality) occurred in the ZMapp group of 36 patients. One patient left treatment early and was not included in the analysis. Although the difference between the two groups translates to a 40% lower risk of death for those who received ZMapp, the difference did not reach statistical significance.

Should new cases of Ebola arise, Mapp Biopharmaceutical has received funding from the US Biomedical Advanced Research and Development Authority to offer ZMapp to patients with confirmed EVD in the four countries where the trial occurred under an expanded access protocol (EAP). Expanded access is a US regulatory mechanism that enables an investigational drug to be made available to treat a serious or life-threatening disease for which no comparable or satisfactory alternative therapy is available. The EAP was reviewed and considered safe to proceed in the US by the FDA. The company will make appropriate regulatory applications on the three West African countries that participated in PREVAIL II as well.