Question Period Note: ACCESS TO TREATMENTS FOR COVID-19

• What is Health Canada doing to help Canadians get access to treatments for COVID-19?

KEY MESSAGES
• Health Canada is expediting the review of all treatments for COVID-19 while continuing to ensure that these products meet standards for safety, effectiveness and quality.
• In September 2020, I signed an Interim Order that created a mechanism for the expedited review of treatments, while ensuring that we maintain a high level of scientific scrutiny.
• As of June 2021, 16 submissions have been received under the Interim Order – including 9 treatments.
• Health Canada has authorized three drugs to treat COVID-19: bamlanivimab and remdesivir were authorized in 2020 and on June 9, Health Canada authorized casirivimab and imdevimab as a combination therapy.
• As of June 10, 2021, Health Canada continues to review 6 treatments under the Interim Order. These include 4 monoclonal antibody therapies (Eli Lilly’s estesevimab and bamlanivimab combination, GSK’s Sotrovimab, CytoDyn’s Leronlimab and Celltrion’s Regdanvimab) and 2 others that work as antiviral and/or anti-inflammatory drugs (favipiravir and baracitinib). One submission, for colchicine, has been withdrawn by the manufacturer.
• The Government of Canada 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 BAMLANIVIMAB
• Health Canada is aware that US FDA has revoked the Emergency Use Authorization for bamlanivimab, at the request of Eli Lilly
• This revocation is related to lack of efficacy against emerging variants of concern circulating in the US, in particular the Californian variants (B.1.427/B.1.429)
• There are no safety concerns with bamlanivimab. This decision was made in the context of the US having two combination monoclonal antibody treatments available, which work better against some of the emerging variants
• In Canada, bamlanivimab has been distributed to all Provinces except Manitoba, New Brunswick and the Territories
• Bamlanivimab is the only treatment currently available in Canada for mild-to-moderate COVID infection
• The Alpha (B.1.1.7) variant is the predominant variant in 94% of the cases in Canada at this time, against which bamlanivimab is expected to retain efficacy
• However, other variants resistant to bamlanivimab are emerging, and Health Canada continues to monitor these variants and their potential impacts on COVID-19 treatments
• Health Canada has updated the product labelling for bamlanivimab and communicated to healthcare professionals to provide information on variants and their impact on bamlanivimab efficacy, and has also discussed this issue with the provinces and territories.

IF PRESSED ON CASIRIVIMAB AND IMDEVIMAB
• On June 9, 2021, Health Canada authorized a new treatment, casirivimab and imdevimab 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.

• The combination drug treatment was developed by U.S. company Regeneron Pharmaceuticals Inc. and is distributed in Canada by Hoffmann-La Roche Ltd.

IF PRESSED ON REMDESIVIR
• Health Canada has 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. We approved this drug with conditions for the manufacturer to ensure its continued safety, efficacy and quality.
• Despite the World Health Organization’s (WHO) updated guidelines advising against the use of remdesivir, Health Canada continues to support this drug as a treatment option, which is in line with other international regulators.
• Specifically, remdesivir modestly decreases patient time in hospital and continues to provide benefit for patients and health care systems when used according to the authorized indication.
• Health Canada will continue to evaluate the information about remdesivir, and will take the appropriate steps to ensure the health and safety of Canadians.

IF PRESSED ON TREATMENT AVAILABILITY
• Health Canada is closely monitoring global treatment development and is in active discussions with manufacturers and researchers to provide regulatory and scientific advice for Canadian clinical trials and regulatory approvals.
• As of June 10, 2021, Health Canada has received 16 submissions under the interim order. This includes 9 treatments and 7 vaccines (Moderna, Pfizer, AstraZeneca, Janssen, Verity Pharmaceuticals/Serum Institute of India, Novavax and Medicago). One of these submissions (for colchicine) was withdrawn on June 7, 2021.
• On November 20, Health Canada, under the Interim Order, authorized a monoclonal antibody from Eli Lilly.
• There are terms and conditions associated with the authorization. This means that there are requirements for the company after authorization to provide additional data pertaining to the quality, effectiveness and safety of the drug.
• While recognizing the urgent need for treatments, all products will undergo a rigorous scientific review to ensure they meet standards for safety, efficacy and quality.

IF PRESSED ON INTERIM ORDER
• The Interim Order allows Health Canada to expedite the review and authorization of drugs and vaccines for Canadians in four ways:
o authorizing a brand new drug based on available evidence with more agile administrative and application requirements;
o authorizing a new drug based on certain elements being approved by a trusted foreign regulatory authority;
o allowing expanded use of an already-approved drug to include COVID-19-related indications that were not in the original authorization; and,
o permitting the Public Health Agency of Canada (PHAC) to arrange for the importation of promising COVID-19 drugs for placement (pre-positioning) in Canadian facilities prior to their authorization in Canada if the Government of Canada has entered into a contract for its procurement.
• Health Canada will ensure that these drugs are supported by sufficient evidence of safety, efficacy and quality.
• In addition, under the Interim Order, Health Canada can impose terms and conditions on the authorization, such as risk mitigation measures and periodic assessments of safety information.
• Health Canada will monitor the safety and effectiveness of these drugs and will take immediate action, including the suspension or cancellation of authorizations or establishment licenses, if required, to protect the health and safety of Canadians.

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 World Health Organization, 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.

IF PRESSED ON THERAPEUTIC INVESTMENTS
• The Government of Canada is collaborating with academia and the private sector to advance research and development of therapeutics including pre-clinical research, bio-manufacturing and enhancing capacity for and access to clinical trials.
• The Government of Canada is closely monitoring and reviewing emerging evidence on possible COVID-19 treatments, such as corticosteroids, antiviral drugs and antibody treatments.
• Health Canada and the Public Health Agency of Canada are working closely with provinces and territories to ensure rapid and equitable access to therapeutics.

BACKGROUND
New Legislative Authorities
In order to be able to take rapid action, on March 25, 2020, amendments to the Food and Drugs Act and the Patent Act were passed that will streamline processes and provide the Government with additional powers.
The amendments will:
• help prevent and mitigate shortages of drugs and medical devices;
• seek additional information from companies to confirm that products are safe for Canadians; and
• allow making, using, or selling a patented invention, such as a medication, that is needed to respond to this pandemic.

Interim measures are also improving access to products that are approved or registered in other jurisdictions with similar regulatory frameworks and quality assurances, but may not fully meet some of the regulatory requirements under the Food and Drugs Act — such as packaging requirements.

Stakeholder Engagement
Information about health products for COVID-19 has been consolidated into a new 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.

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.
Bamlanivimab
On November 20, Health Canada authorized the Eli Lilly drug bamlanivimab for the treatment of adults and pediatric patients 12 years of age or older with mild to moderate COVID-19, who weigh at least 40 kg and who are at high risk of progressing to severe COVID-19 illness and/or hospitalization.

Bamlanivimab is the first treatment to be authorized in Canada using the Interim Order pathway for COVID-19- drugs and vaccines. Under the Interim Order, there are terms and conditions associated with the authorization. This means that there are requirements for the manufacturer after authorization to provide additional data pertaining to the quality, effectiveness and safety of the drug.

The Institut national d’excellence en santé et en services sociaux (INESSS) has published a report on healthcare system implementation that concluded that there is insufficient data to support the use of bamlanivimab in the treatment of COVID-19. Similarly, the Canadian Agency for Drugs and Technologies in Health (CADTH) released a report with their recommendations on January 14, highlighting limited data and issues of bringing COVID-19-positive patients into healthcare settings to receive infusions, which could impact delivery of care to non-COVID patients.
While Health Canada assesses the benefit/risk balance of new treatments based on their safety, efficacy, and quality, INESSS and CADTH conduct independent cost-benefit analyses of new treatments that consider other information in addition to safety and effectiveness. Given their regional mandate for drug use and reimbursement, INESSS’s and CADTH’s recommendations may be different from Health Canada.
Hoffman-La Roche’s 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.

Other antibody products under review
Health Canada has also received four other submissions for antibody treatments with proposed indications similar to Bamlanivimab and Hoffman-La Roche’s casirivimab and imdevimab combination (Eli Lilly’s estesevimab and bamlanivimab combination, CytoDyn’s Leronlimab, GlaxoSmithKline’s sotrovimab and Celltrion’s Regdanvimab). Monoclonal antibodies are being tested both as treatment for mild/moderate COVID-19, and also as prophylaxis, to prevent infection.
Remdesivir
Health Canada has authorized with conditions the drug remdesivir (brand name Veklury) manufactured by Gilead Sciences Canada, Inc. for the treatment of patients with severe symptoms of COVID-19 who have pneumonia and require oxygenation. As a condition of authorization, the manufacturer will submit to Health Canada:
• post-market safety monitoring reports, as well as reports on all serious adverse drug reactions, annual pregnancy safety reports and any foreign regulatory actions related to the safety of remdesivir;
• any further data on the safety and efficacy of the drug, including final data from ongoing clinical trials and additional safety data on patients with liver and kidney disease; and
• further quality data confirming that the manufacturing processes and controls will consistently produce product of suitable quality for the intended use.

Remdesivir has also been granted emergency or conditional authorization in the U.S., Europe, Japan, Singapore, Switzerland and Australia, and the US FDA has granted it full authorization. In Canada, the authorization included a full scientific review. There is no expiry date on the authorization.

One existing clinical trial authorized by Health Canada to evaluate the safety and effectiveness of remdesivir for use in Canada is still ongoing. This clinical trial will continue to gather more data on the drug.

On November 20, the World Health Organization (WHO) released a guidance document, which conditionally recommends against the use of remdesivir in patients with COVID-19, regardless of disease severity. This follows the release of the WHO’s Solidarity trial results, which indicate that remdesivir appeared to have little or no benefit for hospitalized patients.

Health Canada’s authorization with conditions of remdesivir was based on the National Institute for Allergy and Infectious Diseases (NIAID)’s Adaptive COVID-19 Treatment Trial (ACTT-1) trial results and is limited to patients with severe COVID-19 who have pneumonia requiring supplemental oxygen. The large, randomized controlled trial ACTT-1 demonstrated clear clinical benefit for this subset of COVID-19 patients.

Health Canada continues to support the use of remdesivir according to its authorized indication and in the context of clinical trials. Health Canada has not authorized the routine use of remdesivir in patients outside these two scenarios.
Two new variants of SARS-CoV-2 have emerged in the UK and South Africa but the activity of remdesivir against these new variants is not expected to be affected. Health Canada has contacted Gilead Sciences for information on how they plan to assess the impact of these mutations on the efficacy and safety of remdesivir. Regulatory action is not expected to be required at this time, which is consistent with other international regulators.
Favipiravir
Favipiravir is a broad-spectrum antiviral drug that has not been authorized in Canada.
There are currently two authorized clinical trials with favipiravir with study sites in Canada, which have been sponsored by Appili Therapeutics Inc:
• The CONTROL trial is studying its use in preventing COVID-19 outbreaks in long-term care homes. This study is led by Dr. Alison McGeer, an infectious disease specialist in the Sinai Health System.
• The PEPCO trial is studying its use in preventing COVID-19 in vulnerable people who have had recent direct exposure to someone with a confirmed COVID-19 infection.

On December 18, 2020, Dr. Reddy’s Laboratories filed a submission to Health Canada for favipiravir (brand name Reeqonus) for the treatment of COVID-19 under the interim order pathway.
Colchicine
The purpose of this application under the Interim Order was to obtain a market authorization for the indication “reduction of complications in adults with coronavirus infections such as COVID-19.” Although the submission to authorize colchicine as a treatment of COVID-19 has been withdrawn by the manufacturer, colchicine is currently authorized in Canada as 0.6 mg tablets for the prophylaxis and treatment of gout flares and Familial Mediterranean Fever (FMF) in adults at doses up to 2.4 mg daily.
Based on the review of submitted evidence, Health Canada was not able to establish a positive benefit-harm balance for the colchicine 0.5 mg tablets in reduction of complications in adults with coronavirus infections such as COVID-19. The sponsor was given an opportunity to provide additional supporting clinical trial evidence. However, on June 7, 2021, the sponsor opted to withdraw the submission from review. Voluntarily withdrawal of a submission does not disqualify a sponsor from refiling the application at a later date based on new evidence.
Baracitinib
Baracitinib is a Janus kinase (Jak) inhibitor that is already approved in Canada for the treatment of rheumatoid arthritis.

It 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, Eli Lilly filed a drug submission with Health Canada under the Interim Order pathway.

Dexamethasone

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 WHO has updated its guidelines on treating people with COVID-19. Although the dexamethasone study’s results are preliminary, the researchers behind the project suggest the drug should immediately become standard care in severely ill patients.
The oral tablet format of dexamethasone was added to Health Canada’s list of Tier 3 shortages on May 1, 2020 based on its current indications for use. Tier 3 shortages are those that have the greatest potential impact on Canada’s drug supply and health care system. Drugs on this list are in high demand or in shortage. Apotex and Pharmascience are the only two companies in Canada that market the dexamethasone oral tablet. There are currently no active shortages reported by either company. Health Canada is continuing to monitor the supply situation on a monthly basis.
The IV format of dexamethasone has not been determined to be a Tier 3 shortage; a consensus determination was made to monitor the supply situation on a monthly basis. Health Canada is also monitoring the supply situation for dexamethasone alternatives, corticosteroids such as methylprednisolone, prednisolone and hydrocortisone.

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