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Chimerix, Toyama drugs, whole blood and plasma in first Ebola clinical trials

By Nuala Moran
Staff Writer

LONDON – The first clinical trials of experimental Ebola treatments in patients in Africa are poised to get under way at three treatment centers run by Médecins Sans Frontières (MSF) in Guinea and Liberia.

The three separate trials will test two antiviral drugs, brincidofovir (CMX001) from Chimerix Inc., of Durham, N.C., and Toyama Chemical Co Ltd.'s favipiravir, and whole blood and plasma from patients who have recovered from Ebola infection.

Annick Antierens, who coordinates clinical trials for MSF, said the unprecedented international partnership that has speeded things to this point represents hope that patients will finally get an effective treatment against a disease that is killing between 50 percent and 80 percent of those that get infected.

"As one of the principal providers of medical care to Ebola patients in West Africa, MSF is taking part in these accelerated trials to give people affected by the current outbreak a better chance of survival," Antierens said.

The trial protocols are in the final stage of development, with the goal of starting in December and delivering initial results in February 2015. There will be a simple endpoint of 14-day survival, and broad inclusion criteria.

MSF said there will be minimal disruption to patient care and internationally recognized medical and research ethical standards will be applied. All clinical data will be made public.

The outline designs have been approved by the medical authorities in Guinea and Liberia.

MSF said brincidofovir and favipiravir were selected from the World Health Organization's shortlist of potential Ebola treatments after a review of safety and efficacy profiles, availability of product and ease of administration.

Brincidofovir, an oral nucleotide analogue that has shown a broad spectrum of antiviral activity, currently is in phase III for the prevention of cytomegalus infection in immune-compromised patients undergoing bone marrow therapy, and in adenovirus infections.

The drug already has been used to treat several Ebola patients through an emergency investigational new drug application and the U.S. Centers for Disease Control and Prevention has carried out in vitro work suggesting the drug is active against Ebola. Based on that, the FDA recently approved a phase II trial in Ebola.

Favipiravir, also a broad-spectrum antiviral, was approved by the Japanese government for stockpiling against an influenza outbreak earlier this year. It also was approved for emergency use in France to treat a nurse who contacted Ebola while volunteering for MSF.

The trial of brincidofovir will be led by Peter Horby, of Oxford University, and will take place at MSF's treatment facility in Monrovia, Liberia, while the favipiravir study will be run by researchers from the French National Institute of Health and Medical Research (INSERM) in in Guéckédou, Guinea.

Horby said conducting clinical trials of nonapproved drugs in the midst of a humanitarian crisis is a new experience for all concerned. All the partners in the expedited trials have "stepped out of their comfort zones" in order to fast track the studies, he said.

Denis Malvy, who is heading the INSERM trial, said the three trials will be closely coordinated so that any new data can be discussed and the trial designs adopted accordingly. "Strengthening the link between our teams is all the more important as there is the possibility that, should our trials give positive results, the next phase could consist of [combination] therapies."

A third European institute, the Antwerp Institute of Tropical Medicine, will lead the trial of convalescent whole blood and plasma therapy at the Donka Ebola center in Conakry, Guinea.

The MSF is urging Chimerix and Toyama to scale up production to ensure there is no gap between the end of trials and large-scale use, if the drugs are found to be effective.

The trials have been funded by a £3.2 million (US$5.5 million) grant from the UK medical charity Wellcome Trust. Jeremy Farrar, the Trust's director said it is a huge challenge to carry out clinical trials under such difficult conditions, but this is the only way to find out whether potential Ebola treatments work.

"While a therapy may not directly reduce community transmission, it would have immense humanitarian value in saving lives and reducing in-hospital transmission," Farrar said. An effective treatment would also encourage people to seek medical care, which would make a very real difference in this outbreak.

Click here for BioWorld's Special Report: The Push to Contain Ebola Virus for a list of vaccines and therapeutics in development.