A promising pipeline of drugs against Ebola virus

I am cautiously optimistic that the current tragedy will be the last major outbreak of Ebola virus disease (EVD). There are a number of promising drug treatments and vaccines that are being developed. These will be rapidly pushed through clinical trials. The Washington Post had a nice infographic (Figure 1) on some of the treatments (note that a vaccine prevents infection, whereas a treatment tries to eliminate virus in those who are already infected):

Figure 1. A list of anti-Ebola drugs in development to treat Ebola virus infected individuals (Washington Post).

Although the graphic above lists 5 classes, I have reduced the Ebola treatments into three categories of drugs: 1) antisera, 2) viral replication inhibitors, and 3) novel therapeutics.

1. Antisera. Your body produces antibodies against foreign invaders like viruses and bacteria. These antibodies can bind the virus, which either kills or neutralizes it. Someone who survives an Ebola virus (EV) infection possesses lots of antibodies in their blood against different EV proteins. It is possible to purify these antibodies (i.e. make an antiserum) from the blood and inject it into other infected patients to help them battle the virus. Dr. Kent Brantly has been giving his antisera to various EVD patients in the U.S. Indeed there is talk of establishing a program to harvest more antisera from EVD survivors in West Africa.

ZMapp (made by the company Mapp) is a cocktail of three humanized monoclonal antibodies that are targeted against Ebola virus proteins. Injecting this drug into the blood is like giving the patient a "synthetic antiserum". This drug is being produced in tobacco plants (a non-traditional production process) and is in short supply. It has already been given to several patients, and there is anecdotal evidence that it has helped some recover. The preclinical data of ZMapp in monkeys shows impressive efficacy. The U.S. is trying to enlist the aid of larger biotech companies to help make more ZMapp.

2. Inhibitors of viral replication. This class of drugs have had great success against other viruses. They typically inhibit the enzyme (polymerase) that replicates the genome of the virus, thus blocking viral reproduction. Two of these drugs have already been used in Ebola patients: (1) Brincidofovir (Chimerix) and (2) Favipiravir (Fuji). Both were designed to be used against other viruses but have shown "broad spectrum" antiviral activity. As a result, they have already been tested in numerous human subjects which facilitated their use in Ebola patients. Their efficacy against EVD remains to be determined.

3. Novel therapeutics. RNA therapeutics represent a new class of drugs that are composed of RNA (not protein or a small molecule). These RNA molecules are able to inhibit or degrade an RNA target (e.g. viral RNA) in the cell. This can prevent key viral proteins from being made or even target the viral RNA genome. The drug TKM-EBOLA (Tekmira) has had very good pre-clinical data against EVD in monkeys, and it has been administered to some patients although its efficacy is still not known. The drug from the company Sarepta is at an earlier stage of development.

One possibility is that a combination of drugs will be the most effective. Combination therapy has proved to be very potent against both HIV and HCV (Hepatitis C virus) by hitting the virus at several different points in its life-cycle. One drug from each of the three categories would be a starting point for constructing a good drug cocktail.

Finally, the one-two punch of a vaccine and a combo therapy could very well curtail the next EVD outbreak. A vaccine (which I will discuss in another post) would prevent someone from being infected; the treatment would help to cure those who already had became infected. It is most likely that the current outbreak will finally be defeated by public health measures, but perhaps one or two drugs can be rushed out to help in the battle. Any data on drug efficacy and safety will provide valuable information for the future.