The deadliest outbreak of Ebola virus is raging in West Africa, and experimental drugs have shown promise in animal tests.
So why aren’t they being rushed into emergency use?
Until the medicines are shown to be safe for humans, they can’t ethically be used, researchers and drugmakers say. That decision comes at a time when Ebola has killed almost 540 people, or 61 percent of those infected, in an outbreak that according to the World Health Organization may last another three to four months.
“There are survivors of Ebola,” said David Heymann, a professor at the London School of Hygiene and Tropical Medicine who has studied Ebola since the first outbreak in 1976. “Is it ethical to provide a drug when you could be causing a risk to those patients who would survive?”
A safety trial could begin in the first half of next year of an antibody cocktail being developed by the National Microbiology Laboratory in Winnipeg, Canada, the U.S. Army and two drug companies, Mapp Biopharmaceutical Inc. of San Diego and Toronto-based Defyrus Inc., said Defyrus Chief Executive Officer Jeffrey Turner.
An animal study of an earlier version of the cocktail published in 2012 showed all four monkeys that began treatment within 24 hours of being infected by Ebola survived. Additional animal studies are under way and need to be completed, Turner said in a phone interview. The results will be given to U.S. and Canadian regulators early in 2015 before the safety trial can begin, he said.
“We definitely want to advance these drugs, there’s an urgent need, but one needs to be principled and prudent, and first do no harm, even in an outbreak,” Turner said.
Once the treatment is shown to be safe in healthy volunteers, then it can be tested on people with Ebola, said Pierre Formenty of the WHO’s department of pandemic and epidemic diseases in an interview in Accra, Ghana. The agency is playing a coordinating role in responding to the Ebola outbreak, and organized a meeting last week in Accra, Ghana, of health ministers and non-government groups on the outbreak.
“We need to show that there is no adverse event, and after that, we will probably do a trial in the field,” Formenty said. “We have the data showing that it protects a solid number of monkeys that you are inoculating with Ebola, so it’s promising.”
The cocktail is based on the way the immune system works. The treatment contains antibodies that mimic substances produced by the immune system in response to an attack. The antibodies in the cocktail attach themselves to the surface of the virus, making it more vulnerable to the body’s defenses.
The development of such treatments for Ebola should be accelerated, said Jeremy Farrar, a former infectious-disease researcher who is now director of the Wellcome Trust, a London-based medical research charity.
“It would be unethical not to acknowledge that potential new treatments could both save lives and reduce transmission in this and future outbreaks,” Farrar said in an e-mailed statement.
Waiting until next year to start the safety trial and subsequent studies may be a missed opportunity, Farrar said. Once the safety has been proven, the only way to test the drug’s efficacy will be if there’s an outbreak of Ebola, as there is now.
Still, the experience of Tekmira Pharmaceuticals Corp. shows that regulators tread cautiously.
The Vancouver-based company began a safety study in January of its Ebola therapy after it showed success in animals, and the U.S. Food and Drug Administration in March granted the drug a “fast track” designation to expedite review. Last week the FDA placed the trial on hold as it requested more information to ensure the drug is safe at higher doses.
Health officials in the affected countries haven’t asked for the drugs to be used. The FDA hasn’t received any requests for emergency use of experimental Ebola treatments, Tara Goodin, a spokeswoman for the agency, said by e-mail.
“It’s not a subject we discussed among colleagues last week in Accra,” Remy Lamah, Guinea’s health minister, said in a phone interview. “It wasn’t part of the agenda.”
The clinical trial planned for next year, and the Tekmira study, are in the first of three phases of human studies typically needed to get new drugs approved.
The U.S. National Institutes of Health’s Vaccine Research Center has also conducted four clinical trials of Ebola vaccines that have been shown to be safe, deputy director Barney Graham said by e-mail. As the drug delivery mechanism wasn’t potent enough, a more powerful version has been developed and tested in monkeys, and new safety trials in humans are being planned, he said.
Any decision to use drugs in an outbreak must involve pharmaceutical companies, sources of funding for the treatments, national governments and regulatory bodies, said Stephan Guenther, head of the department of virology at the Bernhard Nocht Institute for Tropical Medicine in Hamburg, Germany.
“You definitely can’t take an experimental drug now and go to Guinea and give it to patients,” Guenther said. “This requires a long process of discussion.”
Even if the current outbreak is controlled, further epidemics of Ebola and related viruses will inevitably occur, Farrar said.
“We have to plan a better response for next time, including building stockpiles of potential treatments,” he said. “It is a huge undertaking, complex and challenging in many ways. But our ability to control future epidemics may depend on it.”