A Summary of Recent Advances in Ebola Treatment

August 21, 2019

Only two years ago, neither a vaccine cure for the Ebola Virus, nor effective antivirals existed to prevent Ebola Virus Disease. Recovery for those infected was through the strength of their own immune system, and according to the U.S. Centers of Disease Control and Prevention (CDC), doctors treated patients while keeping them well hydrated, and providing supportive care, helping them to breathe to boost the immune system which offered a better chance to fight off the disease. Doctors attempted to give the patients blood serum transfusions from the antibodies of those who survived Ebola. The current wave, 2018-2019, in the Democratic Republic of the Congo (DRC), is the second deadliest ever. Untreated patients have a 70% death-rate; while, vaccinated persons have a 90% survival rate. Last summer, 1,800 people perished in the DRC (World Health Organization and BBC News, August 13, 2019).

Today, two new antibody-based therapies, REGN-EB3, led by Neil Stahl, PhD, Executive Vice President of Research and Development at Regeneron Pharmaceuticals, and mAB114, under the direction of Anthony Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases (NIAID), were recently discovered most effective against the Ebola outbreak in the DRC, based on synthetic, monoclonal antibodies and interruption of the virus life-cycle. Previously, drug treatment, ZMAPP/MAPP of Biopharmaceuticals carried a 49% fatality rate, and Remdesivir from Gilead has a 53% fatality rate. Of the four new treatments, in November 2018, randomized trials in four towns, REGN-EB3 and mAB-114 proved most effective. Regeneron’s REGN-EB3 is most recommended with 29% fatality rate reduction; followed by NIAID’s mAB114 at a 34% rate reduction, (BBC News, August 13, 2019). When treated early, the mortality drops to 6%, and 11%, respectively.

Treatment challenges exist, as refrigeration of RGN-EB3 and AB-114 make distribution difficult. Small molecule antivirals serve better in urban and remote areas, not requiring refrigeration, and thus, complementing antibody-based therapies. The virus, moreover, may mutate, becoming antibody resistant; therefore, options are needed.

Meanwhile, Merck vaccine candidate, rVSV-ZEEBOV, showed 100% protection rate, during a Phase 3, single-dose, cluster, randomized, ring trial in Guinea; where 5,837 subjects given the shot were not infected ten days after immunization. V920 (rVSV-ZEBOV-GP) is a recombinant, replication-competent Ebola vaccine, consisting of a vesicular stomatitis which has been genetically engineered to express a glycoprotein from the Zaire strain, provoking a naturalized immune response. The trial was conducted by a team of researchers from the WHO, the Norwegian Institute of Public Health, the Health Ministry of Guinea and Médecins Sans Frontières, among others. “We believe the world is on the verge of an efficacious Ebola vaccine,” said Marie-Paule Kieny, the Word Health Organization’s assistant director-general for health systems and innovation (Precision vaccinations, Carlson, Robert & EPG Health, August 2, 2017). Marie-Paule Kieny and Anne Marie Henao Restrepo, et al., performed the first successful Phase 1 and 2 Ebola vaccine clinical trial, March 23, 2016-January 20, 2017, (Lancet, February 04, 2017).

Merck’s clinical trials are in their final stages, and are expected completion by the end of 2020. The vaccine is designed for post-exposure settings, including high fatality adult, maternal and neonatal groups. Screening, population mapping and a ring strategy is performed, identifying high-risk areas. Ebola treatment centers provide, in addition, aggressive rehydration, correction of electrolyte imbalances and nutritional support. This supportive care is a prerequisite to the use of novel therapeutics or vaccines.

Drugs alone will not solve the problem, however, community-foreign preparedness, regional capacity-building, vaccine prevention, surveillance and therapeutic treatment will all be required. The disease is exacerbated, and may continue to spread. Furthermore, due to government instability, war and genocide, lack of education, infrastructure, and cultural beliefs fostering mistrust in vaccines, healthcare workers and a general lack of preparedness, treatment, community engagement and trust building will be essential to effective care provision (New England Journal of Medicine, August 25, 2018).

 

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