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In November 2020, Health Canada authorized the sale and use of bamlanivimab, a monoclonal antibody for the treatment of adults and adolescents 12 years of age and older (at least 40 kg) with mild or moderate COVID-19 who are not yet hospitalized but are at high risk of progressing to that stage.Health Canada (HC) also authorized the sale and use of remdesivir — an anti-viral suitable for adults and adolescents who have been hospitalized with COVID-19, have pneumonia and need oxygen to … Continue readingIt purchased 26,000 doses of the drug therapy at a cost of US $1,250 per dose and shipped 17,000 of them directly to the provinces and territories, and to the Public Health of Canada’s National Emergency Stockpile. The remainder is available for shipping upon request.
According to Health Canada, the use of bamlanivimab falls under the practice of medicine — a provincial and territorial jurisdiction — so the decision to use the drug is “at the discretion of the provinces and territories and health care practitioners.”
“[Health Canada] does not have oversight over the practice of medicine,” said Geoffroy Legault-Thivierge, a spokesperson with the department. “Where activities may be considered the practice of medicine, they are subject to provincial or territorial oversight in Canada. Canadians interested in learning more about possible treatments for COVID-19 are encouraged to discuss it with their health care practitioners.”Currently there are eight therapeutics, including six vaccines, authorized for use in Canada. There are an additional nine anti-viral or monoclonal antibody therapies and two more vaccine candidates … Continue reading
So far, even though bamlanivimab has been authorized for use because of its potential to reduce the need for hospitalization among high-risk COVID patients — and according to the manufacturer has been given to over 400,000 patients in the US alone — it has hardly been used on anyone in this country.
A ‘proactive and proven’ approach
Bamlanivimab (Bam) is a monoclonal antibody that was developed by Vancouver-based AbCellera Biologics, and is manufactured by pharmaceutical giant Eli Lilly. According to Health Canada the authorization of the drug is based on “limited data” that suggests “a potential benefit for patients in the high risk category.”
The drug is intended for patients diagnosed with COVID-19 who are not sick enough to be hospitalized but who have some risk factors. Providing them with an intravenous infusion very early in the infection could prevent dire consequences.
“As an antibody therapy, bamlanivimab neutralizes the virus that causes COVID-19 and reduces the severity of symptoms,” said Dr. Carl Hansen,* Director and CEO at AbCellera Biologics. “It does this by binding to the spike protein on the virus, which blocks its attachment and entry into human cells.”
“It takes about 15 minutes to administer via an IV infusion, typically in an outpatient setting,” Hansen explained.
According to Nova Scotia Health (NSH), the drug has not been used in Nova Scotia yet, and the 50 doses available are “available for use in a research setting for patients over the age of 65 in early stages of the disease.”
The understanding within the NSH seems to be that the drug is not useful against variants or among populations under the age of 65.
However, according Legault-Thivierge at Health Canada, bamlanivimab is effective against the B.1.1.7 (UK) variant, which is the main variant circulating in Canada at this time. In the US, where the situation is somewhat different and more variants are in circulation, the Food and Drug Administration recently granted emergency use authorization for a combination of bamlanivimab and etesevimab for the treatment of mild to moderate COVID-19 in non-hospitalized, high-risk, patients.Additional detail from communication with Health Canada: “Health Canada will continue to monitor the safety and effectiveness of bamlanivimab. It is important to note that results of on-going … Continue reading
According to Hansen, the position taken by the NSH is based on “inaccurate” information.
As of May 19, 2021, the data indicate there were a total of 5,000 COVID cases in Nova Scotia, the vast majority of cases (4,914) are the original lineage of the virus, which bamlanivmab is effective against. Variants of concern (VOC) accounted for 86 cases, and of those, 73 were the UK variant (B.1.1.7), which bamlanivmab is also effective against, explained Hansen.
He pointed out that the drug has been authorized for use in people ages 12 and older, so if the virus is now infecting younger people, the drug could be effective to prevent hospitalizations in these younger age groups as well.
As for why it isn’t being recommended for routine use at the provincial level, Hansen had this to say:
The reasons provided mostly cite a lack of clinical evidence for its effectiveness, which as noted is simply inaccurate, and logistical challenges in administering it. Given that overwhelming ICUs and hospitals is one of the pandemic’s greatest dangers, devoting resources to preventing this by administering antibody therapies is a proactive and proven approach. In the US, for example, more than 5,000 infusion locations offer antibody treatments for COVID-19, with health-care workers having treated more than 400,000 people. Medicare even sends emails reminding people that it covers the treatment, and encouraging those with mild to moderate symptoms and a positive diagnosis to consider it. This proactive approach is what we desperately need here in Canada.
According to Dr. Nicole Boutilier, vice president of medicine with Nova Scotia Health, the drug was “authorized for use by Health Canada with terms and conditions: e.g., it may be used within the context of a clinical trial to collect ongoing evidence of efficacy and safety.” Boutilier says that bamlanivimab “was not approved for routine use in Nova Scotia Health” and that it was “approved for use within the context of pragmatic research (for specific populations).”
“An update to our local pragmatic research trial, CO-VIC, is underway to include bamlanivimab use in patients with non-severe COVID-19 [who are] 65 years of age and older in Nova Scotia Health affiliated Regional Care Units OR 18 years of age and older hospitalized for other reasons at high risk for progression (e.g. early transplant),” wrote Boutilier.
According to Hansen, bamlanivimab has been evaluated alone and together with other antibodies in more than 5,000 patients across multiple clinical trials, and is currently authorized for use in more than 20 countries.
“Bamlanivimab alone versus placebo has been shown to reduce hospitalization by 70% in high-risk patients with early COVID-19 infection … across all clinical trials, all COVID-19-related deaths occurred in patients taking the placebo,” said Hansen. “Not a single death occurred in patients who received antibody therapy.”
Hansen seemed to suggest the provinces might be out-of-date in their assessments of the drug. He said, “doctors depend on the recommendations of provincial and territorial health authorities.”
“The lack of use in Canada is appalling and inexcusable. How is it that a groundbreaking therapy, developed here in Canada, is doing so much good outside of this country, and so little good within it? We need to ask more questions about who is making drug-policy decisions, and the real reasons they are being made.” [italics in his original email]
Asked to expand on what these “real reasons” could be, Hansen recommended I speak to Michael McDougall, spokesperson for Eli Lilly.
In an email, McDougall mostly reiterated what Hansen had already told me. He said that in answering questions about why they’re not putting bamlanivimab to use, provincial health authorities have said it’s “logistically complicated” to set up infusion clinics. They also cited a lack of data to support its use, and like Hansen, McDougall points to recently released data showing its effectiveness alone, or in combination with another monoclonal antibody called etesevimab, currently under review by HC, in neutralizing the UK variant, which is the most prevalent variant of concern in Canada.
McDougall suggested the fact that there were 4,674 new cases in Canada on May 21, and 3,122 Canadians in the hospital because of COVID-19 should be enough reason to start using the drug.There is now emerging evidence that ivermectin — an anti-parasitic medication that has been in use for decades — could potentially be used as prophylaxis and treatment for COVID-19. The American … Continue reading
Why hasn’t bamlanivimab been used in Nova Scotia?
According to McDougall, a small number of patients in Canada have received bamlanivimab. This trial in British Columbia’s Fraser Valley began in April of this year, and there have been uses in Alberta (another trial) as well as in Ontario. “Some patients in Canada have received bamlanivimab, but the number remains quite small despite the availability of this medicine,” MacDougall said.
According to NSH’s Dr. Boutilier, doctors in Nova Scotia hospitals are being provided guidance on how to treat COVID-19 patients by the COVID-19 Therapeutics and Prophylactics Advisory Group, which was established “to provide recommendations to the health system regarding clinical use of antiviral and immunomodulatory agents for treatment of COVID-19 based on evolving evidence and research.” All provinces and territories have similar advisory groups set up to make recommendations.
The Nova Scotia Advisory Group is co-chaired by Infectious Diseases expert Dr. Lisa Barrett, and Clinical Infectious Diseases Pharmacist Dr. Tasha Ramsey, both of whom are non-voting members. Additionally, there are seven voting members and six “stakeholders” with representation from several specialties and professions including physicians, pharmacists, ethicists, and researchers that work for PharmaCare, Nova Scotia Health, and the IWK.
According to “NS Health COVID-19 medication recommendations,” bamlanivimab can only be used here “in the context of pragmatic research.”
To help make some sense of why bamlanivimab hasn’t been put to use on a routine basis in Nova Scotia, I reached out to Dr. Lisa Barrett, who co-chairs the provincial Advisory Group. Barrett was also part of the Canadian Therapeutics Taskforce in April 2020 — a national group that was involved in assessing and recommending bamlanivimab as well as other COVID-19 therapeutics for approval and procurement by HC.
Barrett explained that currently in Nova Scotia, in addition to standard of care drugs like steroids (dexamethasone) the medications that the federal government procured for COVID-19, and provided to the provinces, are bamlanivimab, remdesivir, and tocilizumab. The latter two are recommended for the treatment of severe COVID-19 in patients who have already been hospitalized.
By binding to the virus itself, preventing it from getting into cells, bamlanivimab can “reduce the amount of virus that can set up infection and therefore it has been studied and basically the take home message is, once you’ve actually got quite progressed symptoms, it doesn’t work, it’s too late, the virus has already set up shop. So it is most useful for prophylaxis or the prevention of disease if somebody has been exposed or possibly exposed.”
Barrett said that in people who were very old or at high risk due to co-morbidities, there might be a chance they may not progress further if they receive the treatment. However, she said, “they have to be found and identified at a very early stage, and that is in the community, not within hospital.”
In other words, if someone shows up at an emergency ward with COVID-19 “chances are you’ve missed the boat because they’ve already gotten enough symptoms to be sick enough that they need other stuff,” Barrett explained. “We have dexamethasone, we have tocilizumab, we have remdesivir, all of which are available to people.”
According to Barrett, the use of bamlavinimab requires early surveillance “before people are even barely sick in the vulnerable population.”
During the spring of 2020, when COVID-19 first emerged in Nova Scotia, bamlavinimab had not yet been an option for high risk groups. By the end of November, when the feds authorized the therapy, Nova Scotia was in the enviable position of not having many cases, but the number started to increase, and by Christmas province-wide restrictions were in place again “to prevent hospitals from becoming overwhelmed and stop the spread of COVID-19 throughout the province.”
Could bamlavinimab have played a role in reducing any of this hardship?
Or what about during the most recent “wave” — one we are still trying to extricate ourselves from? On May 26 — more than four weeks since the government imposed very strict province-wide restrictions — there were 72 people in hospital with COVID-19, 19 of whom were in ICU. A total of 79 people have died with the disease.
Could the early intervention therapy be of any use?
The answer to this appears to be a complex one, partly related to timing, and partly related to logistics.
Barrett said one of the main drawbacks of the therapy is that it’s administered by IV, which comes with a risk of a rare transfusion-related lung injury. But it might be a risk worth taking, depending on the patient’s “high-risk” status.
“If you were to do this at a mass level, it requires mass infusion clinics which are not only really difficult to set up, but you’re putting people into groups to bring them in to do infusions for people who potentially have been exposed and are incubating. And we don’t want to do that routinely either.”
According to Barrett, last year, before the variants “became a thing” in Canada, bamlavinimab would have been very useful. “I was a huge advocate,” Barrett said. “I said, ‘Figure it out, people. I don’t care if there’s an infusion clinic problem. Figure it out. We may need it.’”
But here in Nova Scotia the numbers never justified infusion clinics, and in the latest wave dominated by the UK variant, Barrett said the monoclonal antibodies would not be as effective, despite AbCellera’s claims that it is. Barrett said the UK variant AbCellera studied was the early UK variant. “There’s a difference between the early UK variant and the late UK variants, and the late UK variants are the February/ March ones and those are the ones that we seem to have in Nova Scotia,” she said.
The other challenge is identifying the high-risk people who have the disease but have not yet shown symptoms. Recall that according to Eli Lilly, bamlanivimab alone versus placebo was shown to reduce hospitalization by 70% in high-risk patients with early COVID infection across all clinical trials, and that all COVID-19 related deaths occurred in patients taking the placebo. Barrett said the people that they actually treated were “almost exclusively very old and very frail, and the way they found these early, early, early people and patients, was to be doing routine testing twice a week in the long-term care homes, doing deep swabs twice a week for the clinical trial.”
“But right now in Nova Scotia, we have a 90% vaccination rate plus in our long term care people who would be the target for bamlanivimab, and they’ve already developed their own antibodies. Their bodies made their own ‘bam,’” Barrett said.
“We’ve gone through that early period post-vaccination and the older people in long-term care facilities who were the highest risk have all gotten their two doses, anyone who wanted them … So the indications where it’s most useful are changing, at least in Canada. In other countries that don’t have vaccine roll outs like ours it’s going to continue to have a bigger role.”
“I was a big fan, I still am a big fan of AbCellera and bamlanivimab. I’m not against it at all. If we had had this wave before people were vaccinated, seven or eight months ago, I would have highly advocated for the use of this medication,” Barrett said.
“But infusion clinics and health systems delivering the drug at the right time, which is very early in the community, was not at capacity at a time when it used to be useful. Right now with a vaccinated population, and monoclones coming on board in very niche circumstances, I do think there’s capacity to do this when it’s going to be needed.”
* as originally published, this article misattributed the quotes from Hansen to a spokesperson at AbCellera.
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|↑1||Health Canada (HC) also authorized the sale and use of remdesivir — an anti-viral suitable for adults and adolescents who have been hospitalized with COVID-19, have pneumonia and need oxygen to help them breathe. The federal government purchased 150,000 vials of remdesivir and the provinces and territories have “withdrawn” roughly 37,735 vials, with the remaining stockpile sitting in distribution centres across the country. Initially allocation was based on COVID-19 hospitalization numbers, but Health Canada says the drug is now being provided upon request.|
|↑2||Currently there are eight therapeutics, including six vaccines, authorized for use in Canada. There are an additional nine anti-viral or monoclonal antibody therapies and two more vaccine candidates “under review.” The vaccines currently authorized for use in Canada include: AstraZeneca Canada’s adenovirus vaccine, Janssen’s adenovirus vaccine, Moderna’s mRNA vaccine, Pfizer Canada’s mRNA vaccine, Pfizer’s mRNA “pediatric indication” vaccine, and AstraZeneca’s COVISHIELD.|
|↑3||Additional detail from communication with Health Canada: “Health Canada will continue to monitor the safety and effectiveness of bamlanivimab. It is important to note that results of on-going trials are pending to confirm the clinical benefit of bamlanivimab. To ascertain the continued quality, safety and efficacy of bamlanivimab, the authorization is associated with terms and conditions. The authorization of bamlanivimab could be revoked at any time if new information does not support the safety and efficacy of the product for Canadian patients. The current terms and conditions require Eli Lilly to collect data, monitor and report on emerging safety issues, to provide monthly safety reports and to have a specific risk management plan for bamlanivimab. Health Canada has reviewed the monthly safety reports submitted by Eli Lilly and has not identified any new safety concerns.”|
|↑4||There is now emerging evidence that ivermectin — an anti-parasitic medication that has been in use for decades — could potentially be used as prophylaxis and treatment for COVID-19. The American Journal of Therapeutics recently published this study which concluded that “ivermectin should be globally and systematically deployed in the prevention and treatment of COVID-19.” A Canadian study, currently underway out of McMaster University, is looking at the effectiveness of three inexpensive, widely available drugs, including ivermectin, for treating COVID-19. The study is funded in part by the Bill and Melinda Gates Foundation. The principal investigator, Dr. Edward Mills, described it this way: “This could be a real game-changer. The need for treatments in early disease is paramount. Evidence is quickly emerging that suggests a number of drugs may have a promising effect on reducing COVID-19 disease severity in patients with mild to moderate disease.” I reached out to Mills for an update on the study and he said, “The trial is ongoing at the moment so there isn’t much excitement to announce right now. Please reach out in another couple weeks and we may have an update.”|