TORONTO – A clinical trial of what was once thought to be one of the brightest hopes for an Ebola drug has been halted after an interim assessment concluded there was no sign the experimental product was offering overall benefit.
Tekmira Pharmaceuticals announced Friday that the Phase 2 trial of its TKM-Ebola drug had been stopped in Sierra Leone. The announcement leaves the drug in limbo.
Tekmira offered no comment on whether it plans to continue to develop the Ebola drug and a sister compound designed to fight infection with Marburg fever, a disease similar to Ebola. The Burnaby, B.C.-based company did not respond to a request for an interview.
When asked by email if the drug should be shelved as an Ebola therapeutic, principal investigator Dr. Peter Horby replied: “It is too soon to say really.”
A scientist who has researched the drug in non-human primates expressed concern about the development, worrying that the decision might scupper a drug he believes shows a lot of promise.
“Knowing the mechanism of how the drug works, looking at all the non-human primate data we have, it’s hard for me to believe that the drug would not be beneficial if used under the right circumstance,” said Tom Geisbert, an Ebola virus expert at the University of Texas Medical Branch in Galveston. Geisbert does not have a financial interest in the drug.
He noted that an improved version of the drug that he and others tested in primates late last year showed greater success than the version that was being used in the trial in Sierra Leone.
And Geisbert said if TKM-Ebola is shelved, the hopes for Ebola treatment will rest almost entirely on one drug, ZMapp — the antibody cocktail created at Canada’s National Microbiology Laboratory in Winnipeg based on antibodies created in Winnipeg and at the U.S. Army Medical Research Institute of Infectious Diseases in Frederick, Md.
“I can tell you (from) all the monkey studies that we do, you’ve got ZMapp and this one. And there’s a gigantic gap between those two drugs in monkeys and everything else…. You’re dropping off a cliff to the next thing down,” Geisbert said.
When the World Health Organization convened a meeting of experts last September to look for treatment options for the then-mushrooming Ebola outbreak, TKM-Ebola was listed as one of the leading candidates among a very small group of potential drugs.
But privately, some scientists have wondered whether the drug would be well tolerated. While it’s not clear whether that became a concern during the clinical trial, the Tekmira statement quotes Horby saying “final conclusions on the efficacy and tolerability of the drug” cannot be made until the data the trial generated are fully analyzed.
A study published in April described using TKM-Ebola on two Americans who contracted Ebola in West Africa and were flown to the U.S. for care. Both survived, but the doctors said they could not determine if the drug had contributed to their recovery. Both also received blood transfusions from Ebola survivors.
Likewise, the doctors could not say if the drug contributed to the severity of symptoms recorded. In one of the patients, TKM-Ebola was discontinued after six days because his condition worsened.
“Future studies with siRNA products should direct attention to the possibility of adverse effects by the mechanism of immune activation,” the physicians wrote in the journal Clinical Infectious Diseases.
The acronym siRNA stands for small interfering RNA, which is the class of drugs to which TKM-Ebola belongs. They work by silencing targeted disease-causing genes.
Geisbert said he has never seen toxicity problems in primates treated with the drug.
Clinical trials are designed with built-in triggers which, if reached, require the research team to pause and re-evaluate. This trial reached one and the conclusion was that “continuing enrolment was not likely to demonstrate an overall therapeutic benefit,” the Tekmira press release said.
Horby, an associate professor of infectious diseases and global health at the University of Oxford, said the researchers must now study the data and interpret the results “in the context of the patient mix and other variables.” He declined to be interviewed.
It is not clear how many patients had actually been enrolled in the trial by the time it was stopped. It was originally designed to test the drug on 100 Ebola patients.
The testing design was unusual. Instead of randomly assigning people to either get the drug or get standard treatment, Ebola patients who were given the drug were compared to previous Ebola patients. The research was funded by Britain’s Wellcome Trust charity.