Drug trials are useless without patients: Ebola and Brincidofovir

Excellent news reported in the New York Times today – Ebola drug trial is halted due to lack of patients. The quicker this virus leaves the West African region alone, the better. But this news is also a somber reflection on drug and vaccine development. As I wrote before, medical trials in countries with declining disease are doomed to fail. You cannot work out if a treatment works if you don’t have the patients to treat.

Before I go any further, I’ll reiterate: of course it’s excellent news that this horrendous virus is finally leaving the people of Liberia alone (and soon Guinea and Sierra Leone). But when the virus comes back in the future1, having new and effective weapons against it could prevent outbreaks happening again at this scale.

Before the 2014 outbreak in West Africa, news of Ebola vaccines was confined to the academic literature. Once the outbreak was in full force we finally decided to pay attention and fire up the drug pipeline. We needed candidate vaccines and drugs ready to go into the field at the beginning.

I admit the example of ZMapp, an experimental antibody cocktail against Ebola, was such a drug candidate. ZMapp was shown to protect rhesus macaques against the virus (albeit during the outbreak) and saw action in the field. The fact that the drug is so difficult to make in large quantities was probably tolerated by its manufacturers because the world had never seen such a large Ebola outbreak. Either way, we still don’t definitively know if it works in people because too few received it.

This newest drug trial closure is different. We’ve known about this one – Brincidofovir – for some time. Brincidofovir is a potent DNA virus growth inhibitor. It’s currently being stockpiled by the U.S. to counteract a smallpox bioterrorism threat. The fact that it works against Ebola in dishes of cells is an oddity (Ebola has a genome made of RNA, not DNA) that we don’t understand. But we know it works.

I’m not angered by the failings of the current trials. Logistics and manufacturing mean that responding to such an unforeseen virus outbreak without a whole bunch of candidate drugs was always going to prove difficult.

But we need to be ready next time. We don’t have time to run the compulsory safety trials while the virus is raging. We need a list of potential drugs and vaccines that we already know are safe in humans. Only then can we ethically test whether they work during the timeframe of an outbreak. And this preparation should also apply to other emerging virus diseases.

If we fail next time, then there’ll be reason to be angry.


  1. The virus is thought to persist in insectivorous bats in the wild. When a virus persists in an animal reservoir, the only way to effectively eliminate it is to vaccinate or kill enough of that species. Both are extremely difficult and undesirable courses of action. With the virus persistent in bats, there is always the potential for human infection in the future.

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