Coronavirus therapeutics: A look at COVID-19 treatments in Canada

After weeks of illness and breathing difficulties, when COVID-19 patient Tony Passarelli was put on a ventilator at the Etobicoke General Hospital in Toronto back in March, doctors had painted a bleak picture for the 52-year-old.

“That night when he got transferred over there, they basically said he’s a very sick man and won’t make it through the night,” his wife Linda Passarelli recalled.

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After seven days of more complications, fever, infections and kidney problems, Passarelli was transferred to the Toronto General Hospital, where doctors put him on the extracorporeal membrane oxygenation (ECMO) machine as a last resort. And that saved his life, his wife says.

“We were ecstatic because we went from absolutely no hope to now that there was hope of him hopefully continuing to fight this virus,” Linda told Global News.

The ECMO machine pumps oxygen through nasal tubes and is being used to treat COVID-19 patients in extremely critical conditions, who are unable to oxygenate their own blood, in intensive care units (ICU).

In less severe cases, however, Canada has authorized two drugs for treating COVID-19 — remdesivir and bamlanivimab — while a number of other therapeutics are also being used and experimented as part of clinical trials across the country.

Here are some of the various therapies that are available in Canada.

Dexamethasone

Dexamethasone, an anti-inflammatory steroid, given orally or intravenously, has become a de facto standard of care for hospitalized COVID-19 patients in intensive care units across the country.

It is a widely available and cheap drug that has long been used to treat other conditions like cancer, arthritis, asthma, blood disorders and inflammatory diseases. It has now shown to be effective in treating COVID-19.

In June, a clinical trial of more than 2,000 in the United Kingdom found that the drug reduced the death rate by about one-third in coronavirus patients who required ventilation and one-fifth in those who required supplemental oxygen. The researchers found no effect on patients who did not require respiratory support.

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“Current evidence demonstrates low-dose dexamethasone treatment has a clear benefit for severe hospitalized patients with COVID-19, with the greatest benefit observed for patients that require supplemental oxygen or mechanical ventilation, who are above 70 years,” according to the Public Health Agency of Canada.

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Doctors say dexamethasone has proven to be a very helpful tool and one with which they have decades of experience.

“I think it’s pretty clear that the most helpful drug in treating COVID-19 is dexamethasone,” Dr. Isaac Bogoch, an infectious disease specialist at the University of Toronto, told Global News.

“That’s a pretty strong steroid. And it really seems to reduce the risk of death in people that are sick enough with COVID-19 such that they require supplemental oxygen.

“Any hospital caring for patients with COVID-19 is very likely using a lot of dexamethasone.”

According to the World Health Organization (WHO), dexamethasone is considered to be generally safe, with no serious side effects.

However, prolonged use of more than two weeks may cause glaucoma, cataracts, fluid retention, hypertension, psychological effects, weight gain, or increased risk of infections and osteoporosis, WHO says.

Remdesivir

Remdesivir was the first drug conditionally authorized for use by Health Canada on July 27 for coronavirus patients with severe symptoms.

In September, the country secured a supply of up to 150,000 vials of remdesivir.

Developed by U.S. biopharmaceutical company Gilead Sciences, this repurposed antiviral drug is only administered intravenously, limiting its access to the public.

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It has shown promise in two major clinical trials in Canada, but the CPTG recommends that remdesivir should only be administered as part of a randomized controlled trial.

It had previously been explored in diseases like hepatitis C and Ebola, but did not meet efficacy standards for those illnesses.

On Nov. 20, the WHO advised against the use of remdesivir in hospitalized COVID-19 patients, saying there is currently no evidence that the drug improves survival and other outcomes in these patients.

Bogoch said its efficacy is debatable and the drug is in limited supply. It continues to be used in clinical trials in Canada in health-care facilities where patients can be closely monitored and the license is subject to more data becoming available.

“We are continuing in conjuction with the WHO to randomize patients through the CATCO trial [Canadian arm of WHO’s Solidarity Trial] to remdesivir for select groups and that’s mainly the people who require oxygen but are not critically ill in the hospital,” Dr. Todd Lee, an epidemiologist and attending physician at the McGill University Health Centre, told Global News.

Monoclonal antibodies

Canada is also set to roll out monoclonal antibodies to treat COVID-19 patients.

Bamlanivimab by the U.S. company Eli Lilly is the first coronavirus antibody treatment to be approved in Canada.

The government authorized its use on Nov. 20 for adults and children aged 12 or older with mild to moderate disease but at high risk of progressing to severe illness.

Last week, Prime Minister Justin Trudeau said Canada has secured up to 26,000 doses of bamlanivimab.

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Bamlanivimab is specifically directed against the spike protein of SARS-CoV-2, designed to block the virus’ attachment to and entry into human cells, according to the U.S. FDA.

The therapy is still undergoing additional testing to establish its safety and effectiveness.

Health Canada’s interim authorization of the drug was based on a Phase 2 clinical study in patients with mild-to-moderate COVID-19. The patients treated with bamlanivimab showed reduced viral load and rates of symptoms and hospitalization.

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But experts say there are still questions over its efficacy and use.

“It’s an intravenous infusion and requires specific nursing, pharmacy and physical location resources to administer,” Lee said.

“And I think, within the Canadian COVID-19 research community, there is some question about whether the data is strong enough to go to a more widespread use of that.”

“In order for there to be broader uptake in Canada, we really need to see a more robust Phase III randomized controlled trial.”

Bogoch agreed, saying this type of treatment will have considerable logistical challenges, as the IV setup will require resources, skill and time, which is not easy to do in an outpatient setting.

Convalescent plasma

Convalescent plasma treatment involves taking blood samples from people who have recovered from COVID-19, as these may contain antibodies to fight off the virus, to treat others.

In Canada, convalescent plasma has not been authorized as a treatment option, as its safety and effectiveness for treating COVID-19 have not been fully established.

Currently, it is only being assessed in a nationwide clinical trial, CONCOR-1 study, by the Canadian Blood Services and Héma-Québec.

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Recent studies on convalescent plasma in India and Argentina have shown limited effectiveness.

Experts in Canada say the verdict is still out on this treatment and more research is needed.

“There have been, unfortunately, a couple of recent reasonable-sized, randomized controlled trials which did not show a benefit to convalescent plasma, but they have their limitations in terms of size or in terms of the population,” Lee said.

Bogoch added that it was still important to complete the ongoing studies to see if they come up with different results.

Other promising drugs

Some other promising drugs are also being studied in Canadian-led clinical trials.

Among them is colchicine, which is an anti-inflammatory drug that is orally administered and most commonly used for gout and other inflammatory disorders.

Dr. Jean-Claude Tardif, director of the Research Center at the Montreal Heart Institute, which is conducting the clinical trial along with Hamilton Health Sciences in Ontario, is optimistic colchicine may be a significant asset in the global fight against COVID-19 by reducing inflammatory storms in patients with the disease, preventing hospitalizations and even deaths.

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“Colchicine is a remarkably cost-effective and well-tolerated medication with anti-inflammatory and immunomodulatory properties,” Tardif said in a statement in August.

Lee told Global News there was a lot of interest in that medicine globally.

“The recovery trial in the United Kingdom has also picked up colchicine and will start testing it in the inpatient sphere in conjunction with dexamethasone as a standard of care for patients who require oxygen or who are critically ill.”

Meanwhile, the University of Manitoba and University Health Network in Toronto are also looking at the anticoagulant drug heparin, which is a blood thinner used to prevent blood clots, as a potential treatment for COVID-19.

“The research sphere is very active at present. There’s a lot of Canadian presence in these studies and hopefully we’ll get some answers soon,” Lee said.

© 2020 Global News, a division of Corus Entertainment Inc.

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