Experimental therapies being evaluated to treat Ebola

Experimental therapies for Ebola include new compounds, as well as existing drugs approved for other purposes which demonstrate activity in laboratory models and which potentially could be repurposed. At least something is known about the approved drug’s safety profile, though the doses used for Ebola may not be the same.

Each of the following potential therapeutics have been prioritized for consideration based on the availability of non-human primate efficacy data following a challenge from a filovirus (the family of viruses to which Ebola belongs), and justification for a human dose based on preclinical data of the compound or comparative products within that class. The list is organized by the aspect of the virus life cycle that the compound is presumed to disrupt:

1. Targets the virus before it enters the cell.
   1. Zmapp: A cocktail of three monoclonal antibodies, which block or neutralizes the virus by binding to or coating a different site on the covering or “envelope” of the virus.
   2. Hyperimmune globulin: Antibodies that can neutralize the different Ebola virus strains.
2. Interferes with viral production:
   1. TKM 100802: Target two essential viral genes to stop the Ebola virus from replicating
   2. AVI 7537 (Sarepta Therapeutics): molecules that bind viral RNA, blocking gene function
   3. Favipiravir T705 Disrupts enzymes that the virus uses to make copies of itself
   4. BCX4430 (Biocryst). Disrupts enzymes that the virus uses to make copies of itself
   5. Brincidofovir: Disrupts enzymes that the virus uses to make copies of itself
3. Prevents virus from exiting host cells:
   1. No candidates yet, but this an area of active investigation
4. Bolsters human cell’s immune response
   1. Interferons: Induce an antiviral state in exposed cells and regulates the immune system
5. Testing existing drugs approved for other purposes
   1. A number of partners are testing a variety of libraries of existing compounds to see if compounds with potential come to light
6. Whole blood transfusion and convalescent plasma

Characteristics of the potential therapeutics affecting delivery or storage

In addition to the laboratory evidence for activity against Ebola virus, there are other considerations that may affect the potential utility of a therapy in the field. For instance, a compound may require specialized equipment to be administered and may require considerable time and attention for delivery and administration by healthcare workers. It must be remembered that healthcare workers have a number of other tasks providing essential supportive care at the same time and because of the dangers associated with overheating — particularly in the personal protective equipment for safety— can only operate within the care environment for short periods of time.

In addition, some products may have stringent cold chain requirements; and there may be issues of scaling up and availability. Some of these compounds are available in very short supply; some are virtually exhausted. These issues will need to be addressed in order to examine some of these in the field or in order to scale up.

Note: the following table contains examples of the therapeutics under review, but is not ordered, prioritized or complete.

Note: since the ASMTH meeting, MSF has announced that studies of convalescent plasma, brincidofovir and favipiravir will be performed at MSF sites.

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Global Health Strategies generously supported Theo Smart’s attendance at the 63rd Annual American Society of Tropical Medicine and Hygiene Conference in New Orleans.

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