EBOLA Prevention and Treatment Update

In the current Ebola outbreak in the Democratic Republic of the Congo (DRC), four drugs were tested as treatment for the viral infection. Two are mixtures of three monoclonal antibodies for the Ebola virus. REGN-EB3 is being developed by Regeneron Pharmaceuticals and porgaviximab (ZMapp) is being developed by Mapp Biopharmaceuticals. A single monoclonal antibody to treat Ebola, mAb114, was discovered by the National Institute of Allergy and Infectious Diseases and licensed to Ridgeback Biotherapeutics for development. The fourth drug is remdesivir, a small molecule anti-viral being developed by Gilead Sciences.

During the 2014-2016 West African Ebola outbreak, ZMapp demonstrated some hope as a potential Ebola treatment. In a 72 patient, randomized, controlled trial with 72 Ebola infected patients, ZMapp demonstrated a 22% mortality rate compared to a 37% mortality rate in the placebo arm. However, the observed posterior probability of 91.2% did not meet the prespecified statistical threshold for efficacy of 97.5%. In the current DRC outbreak, the Phase II/III PALM trial was initiated to compare REGN-EB3, mAb114 and remdesivir with ZMapp. It was planned that 725 patients would be enrolled. The NIH announced that an interim analysis of 499 patient in the PALM Trial, demonstrated that mortality was 29% after treatment with REGN-EB3, 34% after mAb114, 54% with remdesivir compared to 49% with porgaviximab (ZMapp) in patients infected with the Ebola virus. The trial was stopped early due to superiority of REGN-EB3 and mAb114 compared to porgaviximab. Patients in the safety extension phase of the PALM trial will only be treated with REGN-EB3 and mAb114. Once the trial is completed, an expanded access phase will be initiated for both drugs. A final analysis of the PALM trial is expected to be completed in 4Q19.

Three vaccines are being developed to prevent the transmission of Ebola. The most advanced is the rVSV-ZEBOV vaccine being developed by Merck and New Genetics. The vaccine was originally discovered by the Canadian Public Health Agency. The 1,500 patient, PREVAIL 1 Phase II trial showed an antibody response that was still effective at one year. At the recommendation of WHO, the rVSV-ZEBOV vaccine is being administered in the DRC using the ring vaccination strategy. This strategy involves vaccination of close and high-risk contacts to known Ebola cases along with people with a high risk of exposure such as health workers, ambulance drivers and people who man the safe burial teams.

Johnson & Johnson and Bavarian Nordic are developing the Ad26.ZEBOV vaccine. Ad26.ZEBOV has demonstrated sustained immune responses of 8-12 months in Phase I trials. GSK developed the cAd3-EBOZ vaccine in collaboration with the NIH. GSK licensed the vaccine to the Sabin Vaccine Institute. Sabin has signed an agreement with the National Institute of Allergy and Infectious Diseases’ (NIAID) Vaccine Research Center to develop the drug.

A recent article in STAT news discussed that developing effective vaccines and treatments are just part of the process to control Ebola outbreaks. Problems remain with instability and violence in the areas preventing medical teams from accessing them, changes in burial customs to prevent contact with infected bodies and isolating infected patients.

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