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Stéphane Paquette, director of business development at Appili Therapeutics, seen here behind bottles of tablets to be used in a clinical trial of the drug favipiravir for the prevention of COVID-19.

Tyler Anderson/The Globe and Mail

In April, Armand Balboni received an anxious call from Tokyo.

On the line was a contact from Fujifilm Toyama, the Japanese multinational, who told him that problems were cropping up with a plan to ship 30,000 tablets of the drug known as favipiravir to Canada for a clinical trial.

“It was their head of business development. He said, ‘Can you get somebody to pick up the drug? We’re afraid that the airport is going to shut down tomorrow,‘” recalled Dr. Balboni, who is the chief executive of Appili Therapeutics Inc., a Halifax-based pharmaceutical company.

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What followed was a scramble involving officials on both sides of the Pacific and a middle-of-the-night courier pickup to get the favipiravir from the factory where it was manufactured to a Tokyo airport in time to make one of the last flights to Canada before air travel was halted by the COVID-19 pandemic.

Two months later, those tablets are still sitting in storage in Toronto waiting for doctors to enroll elderly patients in a trial that could begin in a matter of days – but only if outbreaks of the disease start ravaging long-term care facilities as they did in the spring.

“We want to know as quickly as possible whether this [drug] will work,” said Allison McGeer, an infectious disease researcher at Toronto’s Mount Sinai Hospital who is leading the trial. At the same time, she said, “what I’m really hoping is that we don’t enroll anyone.”

The comment illustrates the challenge of finding drugs to thwart COVID-19, particularly for those in the age group that is most at risk of severe illness and death from the disease. On one hand, the quickest way to determine whether a drug is effective is through a randomized controlled trial. But such trials depend on enough people getting infected and possibly dying for a drug to demonstrate its efficacy – something that public-health agencies are working hard to avoid.

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While no one wants a pandemic to last, a drug that might be a crucial weapon against future outbreaks can be left stranded and untested as infections begin to wane.

Favipiravir is a case in point. Developed by the U.S. military for influenza, it is approved in Japan, but only as an emergency remedy against flu strains that are resistant to other drugs. Studies suggest it may work against Ebola.

Like remdesivir, another drug that is showing promise against COVID-19, favipiravir is thought to block polymerase, the enzyme that the virus uses to replicate its genetic material inside host cells.

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Matthias Gotte, a biochemist who works on remdesivir at the University of Alberta, said that, between the two, favipiravir seems to have a weaker effect on COVID-19.

While remdesivir is delivered intravenously, favipiravir can be taken as a pill without the need for a hospital visit. It may therefore offer a way to impede the virus at an earlier stage of infection and prevent outbreaks in long-term care homes. The idea would be to give the drug to all residents and staff as a preventive measure as soon as one resident tests positive for COVID-19.

This picture fits with emerging evidence about where antiviral drugs may prove useful, Dr. McGeer said. While treatments that reduce inflammation, such as the steroid dexamethasone, may turn out to be the best approach for patients battling COVID-19 in intensive care, “in terms of prevention, I think antivirals are likely to be more effective.”

Worldwide, several studies of favipiravir are already under way or planned. On Monday, the drug was approved for “restricted emergency use” as a treatment for COVID-19 in India. But the Appili-sponsored study is the only one specifically aimed at long-term care facilities, where roughly 80 per cent of Canadian deaths from COVID-19 have occurred.

Dr. McGeer initially reached out to Appili when she was looking for someone with a connection to Fujifilm Toyama, which makes favipiravir. Appili, as it turns out, had been in discussions with the Japanese supplier about testing the drug against Lassa fever. Then the pandemic hit and Dr. Balboni found that he was able to arrange a shipment to Canada despite competition from other countries that were lining up to access the drug.

To acquire the data she needs, Dr. McGeer will have to deploy her supply of favipiravir carefully. For the study she is seeking to enroll residents in 16 nursing homes with units of roughly 35 residents each. Then, whenever a COVID-19 outbreak occurs at one of the facilities, half of the time groups will be randomly given favipiravir and half of the time a placebo.

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An open-label study, in which the drug is simply given to all participants, is unlikely to be definitive.

Dr. McGeer added that it would have been ideal if she could have been running the study months ago as outbreaks were peaking. But the drug would not have been available in time and the paperwork and approvals needed to mount the study were completed “at warp speed” to be ready to go this month.

Dr. Balboni said that the current decrease in Canadian case numbers may slow down the clinical trial but the risk of future outbreaks in long-term care is still high enough to expect that the tablets he sourced in Japan will be used.

“We know that this virus is built to infect folks in closed quarters. You just can’t get away from that,” he said.

Sign up for the Coronavirus Update newsletter to read the day’s essential coronavirus news, features and explainers written by Globe reporters.

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