Contracting the Ebola virus has to be one of the absolute worst ways to go. The symptoms start with fever and inflammation. Then comes vomiting, diarrhea and bleeding from bodily orifices. Your organs fail and breathing becomes laboured. Within three weeks, you go into shock and die. Or almost always — the recorded fatality rate approaches 90% in humans.
It is also restricted almost entirely to Africa, which, unfortunately for its victims, makes it a less attractive target for big drug companies than a host of non-fatal diseases (think erectile dysfunction) that are more common in rich countries. It has, however, been the subject of a long-running research project at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) in Maryland, and thanks to a US$140-million agreement with a small Canadian biotech, a cure might be at hand.
News of the deal sent the shares of Tekmira Pharmaceuticals Corp. (TSX: TKM) soaring 40% on the TSX on July 16. Under its terms, the U.S. Department of Defense will fund the development of both a drug and — Tekmira’s real ace in the hole — a delivery technology that has already been shown to halt Ebola in lab animals. “We have an agreement with them where we own the drug, but anything that’s funded by the U.S. government, it reserves the right to use that under certain circumstances,” says Mark Murray, president and CEO of the Burnaby, B.C., company. Those include responding to bioterrorism.
The partnership got its start four years ago, when Ian MacLachlan, head of research at Protiva Corp., which later merged with Tekmira, cold-called USAMRIID’s Tom Geisbert, who had become famous as a “virus hunter” in Richard Preston’s bestseller The Hot Zone. (That book recounted the fight to contain a new strain of Ebola that broke out among monkeys imported to a lab in Virginia in 1989, and a character based on Geisbert was later played by Dustin Hoffman in the fictional movie Outbreak.) MacLachlan wondered whether Geisbert and his army colleagues had considered the emerging field of RNA interference as a way to combat Ebola. His company, he said, had hit upon a way of delivering RNA-based therapeutics into live patients.
“It was just dumb luck at the time that we were interested and even working on it,” recalls Geisbert, today a professor at the University of Texas’s Galveston National Laboratory. RNA is like a simpler form of DNA, which is the blueprint for life. Only in the past decade has RNA been discovered to carry out a wide variety of specific tasks in genetics, such as turning particular genes on or off. RNA interference involves synthesizing short strands of RNA that will turn off harmful genes, such as the ones that allow viruses to spread. Applied to cell cultures in a petri dish, it works. The problem for scientists is that these synthetic molecules tend to get destroyed by the immune systems of live trial subjects.
This is where Tekmira comes in. The company’s core technology is a lipid or fat particle capable of taking the RNA agent to the place in the body where it can get to work. When the institute tried injecting Ebola-infected animals — first guinea pigs, then monkeys — with its therapeutic agent encased in the lipid nanoparticles, the survival rate rose to 100%, from around 20% in previous trials.
Tekmira has two other drugs in development that use the same delivery system and RNA interference technique to combat heart disease and cancer, and it’s testing the delivery of other companies’ therapeutic agents using the lipids. But it is the Ebola treatment that is now fully funded for obtaining U.S. Food and Drug Administration approval, assuming it meets its targets. The program will involve clinical trials testing for safety in humans, followed by a larger trial using non-human primates exposed to Ebola. That’s where things get expensive and ethically tricky, because this time scientists must demonstrate not only recovery in treated animals, but “100% lethality” in the control sample, Geisbert says. “A rhesus monkey costs $7,000. These studies aren’t cheap.”
And while it is the Americans who are funding the science, it’s still not clear who might pay for the drug’s production and how it would be made available in the developing nations that are most in need of it. Still, Geisbert is hopeful that not just U.S. emergency-response agencies but also African hospitals will have a cure for Ebola in their freezers in the not too distant future.