Question Period Note: Paxlovid and other therapeutics for COVID-19

N/A

• The COVID-19 pandemic has created unprecedented challenges to Canada’s healthcare system, and there is a need for treatments to support the response.
• Health Canada is expediting the review of all treatments for COVID-19 while continuing to ensure that these products meet standards for safety, efficacy and quality.
• Health Canada has now authorized several drugs to treat COVID-19, including antivirals (Veklury and Paxlovid) as well as biologic treatments called monoclonal antibodies. These treatments offer more tools in our toolkit against COVID-19.
• Several other treatments to help prevent or treat COVID-19 are under review. All drugs must be subjected to rigorous regulatory review to ensure the product is safe, efficacious and of high quality before being authorized for sale in Canada.
• The Government of Canada has procured many of these treatments and continues to engage proactively with domestic and international companies to negotiate advance purchase agreements for the procurement of treatments to ensure timely access.

IF PRESSED ON PAXLOVID (Pfizer) …
• Pfizer’s Paxlovid is the first oral treatment approved in Canada for non-hospitalized adult patients diagnosed with COVID-19 who are at a high risk of progressing to severe disease. Given its easy administration, it provides another tool in the toolkit against COVID-19 at a crucial time in the pandemic as we are faced with new variants.
• As of July 2022, over 700,000 treatment courses have been allocated across Canada.
• However, no drug is a substitute for vaccination. Vaccination and public health measures remain the most important tools in preventing COVID-19 illness, and we continue to strongly recommend vaccination for all eligible Canadians.
• A small subset of patients experience rebound symptoms shortly after completing a course of Paxlovid and/or test positive in COVID-19 tests after previously testing negative. These reports have been investigated and Paxlovid continues to be a safe and effective treatment for many patients with COVID-19.
• Health Canada will continue to collect information and will take the appropriate steps to protect the health and safety of Canadians.
IF PRESSED ON VARIANTS OF CONCERN …
• Health Canada is working with manufacturers and international regulatory partners, including WHO, to assess the potential impact of the omicron variants on approved test kits, vaccines and treatments, as well as on products under regulatory review.
• As evidence emerges, Health Canada will take action and inform Canadians if there are changes to the safety or effectiveness of COVID-19 health products in Canada because of these variants.
• If new vaccines or treatments are needed, Health Canada will prioritize the reviews to make these products available as soon as possible while maintaining high standards for safety, efficacy and quality.
• Health Canada will continue to inform healthcare professionals and patients if any specific treatment is no longer recommended.

IF PRESSED ON MOLNUPIRAVIR (Merck) …
• Molnupiravir is an oral antiviral treatment that has been reported to show some promise in treating non-hospitalized COVID-19 patients with mild to moderate COVID-19 and at high risk for progression to severe disease.
• Similar to other regulators such as the European Medicines Agency and Swissmedic, Health Canada is working with Merck to obtain further clinical data to further characterize the safety and efficacy of molnupiravir.
• Because this is a rolling submission, Merck is continuing to submit evidence to Health Canada to support the product’s safety, efficacy and quality and Health Canada will conduct a full review of all the evidence prior to making a decision.

IF PRESSED ON IVERMECTIN …
• Evidence from several clinical studies have failed to demonstrate that ivermectin works to prevent or treat COVID-19, and it is not authorized for this use. To date, Health Canada has not received any drug submission or applications for clinical trials for ivermectin for the prevention or treatment of COVID-19.
• A veterinary version of this medication is available to treat parasitic infections in animals. People should not use the veterinary version of this product to treat or prevent COVID-19 or for any other reason. Canadians should never consume health products intended for animals because of the potential serious health dangers posed by them.

IF PRESSED ON INTERNATIONAL COLLABORATION
• Health Canada is leveraging its strong international partnerships with the US Food and Drug Administration, the European Medicines Agency, and the Access Consortium, amongst others, to share information and to raise our collective level of awareness of evidence-based approaches for treatments. The objective is to work towards alignment on regulatory requirements and to stay informed of any potential treatments.

Stakeholder Engagement

Information about health products for COVID-19 has been consolidated into a website for the health product industry, so they know how to apply for regulatory approval and who to contact for questions. Information relevant to health professionals and Canadians is provided on the COVID-19 website.

Treatments

Dexamethasone
Although not specifically authorized for the treatment of COVID-19, clinical trial results announced in June 2020, showed that dexamethasone, used since the 1960s to reduce inflammation, cut death rates by around a third among the most severely ill COVID-19 patients admitted to hospital. As a result, the World Health Organization’s (WHO) has updated its guidelines on treating people with COVID-19.

COVID-19 Authorized Treatments

Remdesivir
On 27 July 2020, Health Canada authorized the drug remdesivir (brand name Veklury) for the treatment of patients (12 years of age or older, who weigh at least 40 kg) with severe symptoms of COVID-19 who have pneumonia and require extra oxygen to help them breathe. Health Canada approved this drug with conditions for the manufacturer to ensure its continued safety, efficacy and quality. On April 22, 2022, Health Canada authorized the expansion of the indication to include non-hospitalized adults with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death. On August 2, 2022, Health Canada received a new submission to expand the use of remdesivir in paediatrics aged 28 days to 11 years, weighing at least 3kg.

Bamlanivimab
On November 20, 2020, Health Canada authorized the Eli Lilly drug bamlanivimab, a monoclonal antibody. Bamlanivimab was authorized under the Interim Order and is currently under review under the amended Food and Drug Regulations. The updated clinical information is included in the submission under review and will inform the regulatory decision.

Casirivimab and imdevimab combination
Casirivimab and imdevimab are monoclonal antibodies that are administered together by intravenous infusion as a single dose, and this product has shown a clear benefit for patients with mild to moderate COVID-19 who are at high risk of hospitalization and/or death. This combination drug treatment was developed by U.S. company Regeneron Pharmaceuticals Inc. and is distributed in Canada by Hoffmann-La Roche Ltd. A Health Product Risk Communication was posted on January 7, 2022, indicating significantly reduced neutralization potency and a high risk of treatment failure with the casirivimab and imdevimab combination against Omicron.

Sotrovimab
On July 30, 2021, Health Canada authorized Sotrovimab from GlaxoSmithKline. This monoclonal antibody is approved for the treatment of mild to moderate COVID-19 in adults and adolescents (12 years of age and older weighing at least 40 kg) who are at high risk for progressing to hospitalization and/or death. Sotrovimab is not effective against omicron as communicated by both Health Canada (Health Product Risk Communication on April 14, 2022) and the company.

Paxlovid (nirmatrelvir in combination with ritonavir)
On January 17, 2022, Health Canada authorized Paxlovid (nirmatrelvir in combination with ritonavir) for the treatment of COVID-19 in non-hospitalized adult patients at risk of progressing to serious disease including hospitalization and death). Nirmatrelvir is an oral anti-viral drug developed by Pfizer that is co-administered with another drug, ritonavir, which acts as a booster to maintain the required concentration of nirmatrelvir for antiviral effect. Previously, all existing COVID-19 treatments required IV administration or injection in a hospital and clinical setting. Oral anti-virals, such as Paxlovid, can be easily administered at home, thereby reducing the strain on the health care system. There have been some media reports that some patients experience rebound symptoms (i.e., reoccurrence of symptoms) shortly after completing a course of Paxlovid; however, a direct link has not been established at this time.

Evusheld
On April 13, 2022, Health Canada authorized AstraZeneca's Evusheld treatment, a monoclonal antibody for the prophylaxis of COVID-19. Evusheld is a combination of two long-acting antibodies, tixagevimab and cilgavimab, derived from B cells donated by patients recovering from infection with the SARS-CoV-2 virus. Evusheld is recommended for use in adults who are not currently infected with COVID-19 and who are unlikely to mount an adequate response to vaccination against COVID-19, including those for whom vaccination is not recommended.

Additional data is being requested on effectiveness against Omicron. On February 24, 2022, the FDA authorized an increase in dose in response to Omicron subvariants BA.1 and BA.1.1. AstraZeneca noted that they are not proposing a change in dose for their Canadian submission. Evusheld is expected to have greater neutralizing activity against BA.2.Health Canada is currently reviewing a change to the dosing regimen for pre-exposure prophylaxis submitted on July 28th 2022.

COVID-19 Treatment Submissions Under Review

Baricitinib is being investigated as a treatment that may reduce the complications related to the cytokine storm as well as potentially inhibiting cell proteins that have a role in viral replication. On May 13, 2021, Eli Lilly filed a drug submission for baricitinib with Health Canada and as of December 1, 2021, this submission is under review. On June 7, 2022, Eli Lilly filed new data from a recently completed clinical trial and the data is under expedited review in Health Canada.

Molnupiravir is an anti-viral, in capsule form, for the treatment of adults with mild-to-moderate COVID-19 and who are at risk of progressing to severe COVID-19 disease. Merck’s drug submission with Health Canada is under review. The United Kingdom’s (UK) Medicines and Healthcare products Regulatory Agency (MHRA) authorized conditionally the use of molnupiravir on November 4. The EMA issued advice on November 19, 2021, to support national decision-making on the possible use of these medicines before a formal authorization is issued, for example in emergency use situations, while it continues its on-going rolling review for market authorization. On December 23, 2021, the US FDA issued an emergency use authorization for molnupiravir only in patients for whom alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate. Australia’s Therapeutic Goods Administration (TGA) granted provisional approval and Singapore’s HSA granted interim authorization for molnupiravir on January 20 and April 19, 2022, respectively. Swissmedic’s (Switzerland) review for temporary approval and the EMA’s review for conditional market authorization are still on-going.

Health Canada has four other submissions for monoclonal antibody treatments AstraZeneca’s tixagevimab and cilgavimab, Eli Lilly’s estesevimab and bamlanivimab combination, Celltrion’s Regdanvimab and Hoffman La Roche’s Actemra (tocilizumab). Monoclonal antibodies are being tested both as treatment for mild/moderate COVID-19, and also as prophylaxis, to prevent infection.

Tocilizumab (Actemra) is a recombinant humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody of the immunoglobulin (Ig) IgG1 subclass with a H2L2 polypeptide structure that is already authorized in Canada for non-COVID use. On February 4, 2022, Health Canada received a submission for a COVID-19 indication that is under review, and PHAC’s external advisory body (Clinical Pharmacology Task Group) made recommendations for use. FDA issued an Emergency Use Authorization on June 24. On December 6, the EMA recommended approval for certain hospitalized adult COVID-19 patients.

COVID-19 Treatment Submissions Withdrawn

On June 7 2021, the submission to authorize colchicine as a treatment of COVID-19 was withdrawn by the manufacturer. Colchicine remains authorized in Canada for the prophylaxis and treatment of gout flares and Familial Mediterranean Fever. Although unproven at the time, Colchicine was used to treat the Former President Trump and gained a lot of media attention.

The Sanoclear (Nitric Oxide) submission was withdrawn Sept. 01, 2021, with an expectation that it will be refiled once additional clinical data is available, and the leronlimab submission was withdrawn September 16, 2021.

On February 24, 2022, Dr. Reddy’s Laboratories withdrew its submission for favipiravir.

• Health Canada is actively engaging with stakeholders in the health product industry to proactively identify, track and provide support to sponsors of clinical trials and treatments related to COVID-19.
• Health Canada has authorized several drugs to treat COVID-19, including antivirals (Veklury and Paxlovid) and biologic treatments called monoclonal antibodies. These treatments are approved for non-hospitalized patients with mild–to-moderate COVID-19 symptoms and who are at high risk of developing severe disease. Veklury (remdesivir) is also approved for treating hospitalized patients with severe COVID-19 and who require supplemental oxygen. Several other treatments for COVID-19 are under review.
• Pfizer’s Paxlovid is an oral antiviral treatment of adults diagnosed with COVID-19 with mild-to-moderate symptoms and who are at a high risk of progressing to severe disease, including hospitalization or death. Paxlovid is a combination of the oral antivirals nirmatrelvir and ritonavir, which can be taken at home in pre-packaged doses. As an oral drug it is expected to ease the burden on the health care system.
• As of July 28, 2022, 747,042 treatment courses of Paxlovid have been allocated to jurisdictions (including provinces and territories), the Department of National Defense, Correctional Services Canada and Indigenous Services Canada.