From Compound Interest:
The current ebola virus epidemic in West Africa has dominated the news in recent months, and in the past week, several medical organisations have announced their intention to commence trials with possible treatments for the virus in the coming months. Two of these treatments are the anti-viral drugs brincidofovir and favipiravir, chosen due to some promising data on their potential efficacy against the virus, as well as their non-prohibitive costs. Here, we take a look at them in a little more detail.
The first of the two drugs, brincidofovir, was originally developed for a range of DNA-based viruses, such as smallpox and adenovirus. It’s currently in phase III of clinical trials for treatment of these viruses, in which large groups of people are tested, and effectiveness and side effects are monitored.
The use of brincidofovir against the ebola virus is unusual in that it’s usually only effective against DNA-based viruses. These viruses have DNA as their genetic material, commonly in the double-stranded manner we’re all familiar with. Ebola, however, is an RNA-based virus, with single-stranded RNA as its genetic material. Whilst we still don’t know exactly how brincidofovir acts against ebola, in preliminary lab tests on cells it’s been shown to have some effectiveness against the virus, hence its inclusion in the upcoming trials.
Additionally, it’s actually already been used in ebola patients. It was administered to the first US case of the virus, although the patient was already critically ill when given the medication, and it was unable to prevent his death. However, another patient, given brincidofovir in mid-October, was later pronounced clear of the virus.
One of the advantages of brincidofovir over the other potential trial drugs is the fact that it’s already been safety tested in over 1000 humans as part of its trials for use against other viruses. As a result, we have much more data on its activity in the body in a range of patients. What we still don’t know is if the drug is effective in animals infected with ebola.
This is a criteria that is to an extent met by the other candidate for the trials, favipiravir. This drug, developed in Japan, has been shown to be active against a range of viruses, including the influenza and yellow fever viruses. It’s also been shown to be effective against the ebola virus in animal models, with several research papers having been published on its effects on mice infected with the disease.
In favipiravir’s case, we also have a good idea of how it works. It’s thought that it prevents replication of the virus by inhibiting the enzyme, RNA-dependent RNA-polymerase, that allows the ebola virus to duplicate its genetic material. It’s already in phase III trials in the US for treatment of influenza, and has been stockpiled by the Japanese government in case of an influenza epidemic.
In terms of effectiveness against ebola in humans, as with brincidofovir, data is obviously sparse – something the upcoming trials will hope to address. Like brincidofovir, however, it has already been used as an experimental treatment for ebola; it has been reported that a French nurse in Liberia who contracted ebola was given favipiravir after being flown back to France, and subsequently recovered.
An advantage of both of the drugs is that they can be given in the form of pills, making their distribution much easier than intravenous drugs or vaccines should they be shown to be effective. The manner in which the trial will operate differs from the norm; whilst a control group, which does not receive the drug, would usually be used in trials of drug efficacy, this was judged to be unethical in the case of ebola. Instead, all patients who consent to receiving the drug will take part, and results will be analysed after every 20th patient. If there is a vast improvement in the mortality rate with either of the drugs, from the current rate of 70% to 40% or under, the trials will be stopped immediately, and use of the drugs in treating the virus will be fast-tracked.
Should the drugs fail, other drugs have been shortlisted to take their place in trials. Additionally, a third trial is being conducted using blood and plasma containing antibodies from those who have recovered from the disease. It’s hope that data on whether or not the initially selected treatments are effective will be obtained by February; if they are, then a great stride will have been taken towards stemming the tide of the epidemic, though preventing the spread of the disease in the first place will remain the priority.
Compound Interest’s posts are kindly sponsored by P212121, chemical suppliers.
References & Further Reading
- Ebola: experimental drug trials – S Bosely, The Guardian
- Brincidofovir given to patients – D Kroll, Forbes
- Ebola drug from Japan is key candidate – C Koons & others, Bloomberg
- Successful treatment of ebola in an animal model – L Oestereich & others
- Efficacy of favipiravir in a mouse model – S J Smither & others