The Ebola Epidemic Whose Compassionate use Therapeutics will be Tested?
By Dr. Bob Roth, M.D., Ph.D.
Ebola is a rapidly-progressing contagious disease, with high mortality and associated panic. There is no treatment for this viral disease, although experimental therapies are under investigation. With the exception of the current Ebola epidemic in West Africa, there is no consistent underlying incidence of the disease allowing drugs to be prospectively studied in patient populations, and therefore animal models provide the scientific presumptive evidence that a drug might prove effective.
One promising therapy, an RNA interference product in development by Tekmira Pharmaceuticals, has successfully been tested animals and in an ascending dose regimen in healthy volunteers. However, the next planned phase of the trial looking at multiple dose pharmacokinetics and tolerability has recently been placed on hold by FDA due to questions related to mechanism of action, immune responses of concern, and how best to optimally protect the human subjects. A very different experimental drug, a monoclonal antibody therapeutic, which has been given to two exposed American healthcare workers with apparent benefit, has been in the news a lot lately. Interestingly, this drug candidate has reportedly not even entered human testing, and therefore has even less evidence for human safety than the Tekmira product on clinical hold.
As is the case with all experimental drug studies, the basic issue FDA must consider is whether the benefits of the treatment outweigh the potential safety risks. This week, FDA indicated that it intends to work with companies and investigators working with Ebola patients “in dire need of treatment.” Whether the Tekmira Pharmaceuticals drug will qualify for such compassionate use according to this principle is unclear given its current clinical hold state with the Agency, though a petition process may push the consideration into more a political than scientific arena.
The problem with drugs in development for Ebola as compassionate use candidates is that there is so little human experience to date. In past epidemics, such as with H1N1 flu several years ago, emergency use authorization of experimental therapeutics was more readily justified because of the greater pre-existing human use experience. However, a strong case can be made in the case of the Ebola epidemic that the risks of adverse outcomes related to the experimental drug are relatively minor given the alternative that giving nothing more than supportive care equates to a rapidly-fatal clinical outcome in most instances. In our opinion it would be justified to evaluate by compassionate use a wide range of potential Ebola therapeutics with considerations of risk vs. benefit very different from those applied to typical IND studies.
Dr. Bob Roth, M.D., Ph.D. is Vice President and Worldwide Medical Director at The Weinberg Group, the world’s leading food and drug consulting firm. If you have any questions, please contact us.