Question Period Note: ACCESS TO TREATMENTS FOR COVID-19

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

• 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, I signed an interim order that creates a mechanism for the expedited review of treatments, while ensuring that we maintain a high level of scientific scrutiny.

• As of the beginning of December, 5 submissions have been received under the interim order – including 1 treatment and 4 potential vaccines.

• On November 20, Health Canada issued its first approval under the interim order for a treatment using a monoclonal antibody from Eli Lilly (bamlanivimab). Canada has secured access to 26 000 doses of bamlanivimab over the next three months and expects to receive the first shipment in December 2020.

• We have also authorized, with conditions, the drug remdesivir for the treatment of COVID-19. In September, the Government of Canada secured 150,000 vials of remdesivir for Canadians. Initial shipments to Provinces and Territories began in September and will continue into 2021.

• The Government of Canada continues to proactively engage with domestic and international companies to negotiate advance purchase agreements for the procurement of treatments to ensure timely access.

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.

Clinical Trials

Health Canada is facilitating clinical trials related to COVID-19 in Canada. Clinical trials are conducted to determine whether new drugs, diagnostics or treatments are both safe and effective in human beings. Several existing drugs have been repurposed to assess their potential in treating or preventing COVID-19, while other new drugs are under development. Health Canada recommends that any treatments be investigated in clinical trials.

Clinical trial applications will be reviewed and approved by Health Canada in under 15 days. As of December 1, 2020, Health Canada has authorized over 70 clinical trials for treatment or prevention of COVID-19, most of which are repurposing existing drugs.

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 product 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.

Bamlanivimab has received Emergency Use Authorization from the US FDA.

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. In Canada, the authorization included a full scientific review. There is no expiry date on the authorization.

Two existing clinical trials authorized by Health Canada to evaluate the safety and effectiveness of remdesivir for use in Canada are ongoing. These clinical trials 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. The European Society of Intensive Care Medicine (ESICM) is also recommending against the routine use of remdesivir in COVID-19 patients, according to an interview with the ESICM President published in Reuters on November 13, 2020. These recommendations follow 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.

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. 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.

Apotex and Pharmascience are the only two companies in Canada that market the Dexamethasone oral tablets. Apotex is reporting a shortage for the 0.5mg strength with an estimated end date of October 30, 2020. Apotex is not reporting any shortage for the 4mg strength. Pharmascience is reporting shortages for the 0.5mg strength with an estimated end dates of November 23, 2020 and for the 0.75mg, 2mg and 4mg strengths with an estimated end date of December 7, 2020. Health Canada continues 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.

Hydroxychloroquine

Hydroxychloroquine is an antiparasitic drug approved in Canada for the treatment of malaria, as well as autoimmune diseases such as rheumatoid arthritis and lupus. Health Canada has authorized clinical trials on the use of this drug in COVID-19, and is aware of other ongoing clinical trials across the world.

• An article in the May 22, 2020 edition of “The Lancet” features a study which showed increased mortality and cardiac arrhythmias in hospitalised patients taking chloroquine and hydroxychloroquine for the treatment of COVID-19. This paper was later retracted amid concerns with the validity of the data.
• On June 3, a Canadian-led study published their results in the New England Journal of Medicine, concluding that HCQ did not prevent infection when used as post-exposure prophylaxis within 4 days after exposure.
• On June 5, Investigators of the RECOVERY trial (the UK arm of the SOLIDARITY trial) issued their preliminary results and concluded that there is no beneficial effect of HCQ in patients hospitalized with COVID-19. As such, they have decided to stop recruitment to the hydroxychloroquine arm of this trial.
• On June 17, 2020, the World Health Organization announced that hydroxychloroquine will no longer be part of its global SOLIDARITY trial. Their decision was based on the evidence that hydroxychloroquine in that trial did not result in the reduction of mortality of hospitalized COVID-19 patients, when compared with standard of care. This decision does not impact other ongoing clinical trials.

SYNOPSIS

• The COVID-19 pandemic has created unprecedented challenges to Canada’s medical system, and there is a need for treatments to support the response.
IF PRESSED ON BAMLANIVIMAB

• Health Canada has 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 product 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.

• In a clinical study, treatment of high-risk patients with bamlanivimab reduced the proportion of COVID-19-related hospitalization or emergency room visits compared to placebo-treated subjects.

• Health Canada conducted a scientific review for safety, effectiveness and quality, and determined that the benefits of bamlanivimab outweigh its risks when used according to label instructions.
IF PRESSED ON REMDESIVIR

• Health Canada has authorized the drug remdesivir (brand name Veklury) for the treatment of patients 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.

• Health Canada is aware that the World Health Organization (WHO) has updated its guidelines advising against the use of remdesivir in hospitalised patients with COVID-19, regardless of disease severity.

• However, Health Canada’s position, which is aligned with other international regulators including the European Medicines Agency, is that remdesivir has shown modest but convincing evidence of decreased time in hospital and continues to provide benefit for patients and health care systems when used according to the authorized indication.

• Health Canada recognizes that conflicting expert recommendations on the use of remdesivir may be causing confusion for healthcare practitioners. The Summary Basis of Decision, which summarizes the evidence used by Health Canada to approve remdesivir, is available online.

• Health Canada will continue to evaluate the information about remdesevir, 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 mid-November, Health Canada has received 5 submissions under the interim order. This includes 1 treatment – a monoclonal antibody from Eli Lilly, and 4 potential vaccines (Moderna, Pfizer, AstraZeneca, and Janssen).
• 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 licences, if required, to protect the health and safety of Canadians.
IF PRESSED ON CLINICAL TRIALS AND POTENTIAL TREATMENTS

• Health Canada recommends that any potential treatments for COVID-19 be investigated through clinical trials. Clinical trials ensure the quality of the study, protection of the patient, and the proper collection and retention of outcomes. It is the best mechanism to provide trial volunteers access to new drugs before they are approved.

• The Department is working tirelessly to facilitate and expedite as many clinical trials for COVID-19 in Canada as possible, without compromising their quality. To this end, in May I approved an Interim Order that supports clinical trials. Among its benefits, the Interim Order reduces the administrative burden for sponsors without compromising the safety of participants, and makes it easier to set up trials across Canada to facilitate access.

• As of December 1, over 70 clinical trials have been authorized in Canada, including 15 under the Interim Order.
IF PRESSED ON POTENTIAL DRUG TREATMENTS AND UNAPPROVED PRODUCTS

• Results from large, well-designed clinical trials are needed to make any conclusions on the safety and efficacy of any treatments.

• Health Canada is expediting the review of clinical trials so that products can be studied and made available to Canadians as quickly as possible.

• As new data about these novel treatments becomes available, Health Canada will continue to take the appropriate steps to ensure the health and safety of Canadians.
IF PRESSED ON DEXAMETHASONE

• Treatment with dexamethasone has been shown to reduce the number of deaths for severely ill COVID-19 patients.

• Dexamethasone is a relatively inexpensive steroid drug that has been shown to reduce the number of deaths for some severely ill COVID-19 patients. It is available in Canada and can be used off-label by physicians to treat these patients.

• Health Canada is actively monitoring supplies of this drug in Canada and is in contact with the manufacturers to assess current supply levels. The Department will take action if needed, in collaboration with the provinces and territories, industry and key stakeholders, to help ensure continued supplies of dexamethasone in Canada.
IF PRESSED ON HYDROXYCHLOROQUINE

• Hydroxychloroquine is a malaria drug being investigated as a potential treatment for COVID-19 through clinical trials. Some trials have been discontinued but others are proceeding, depending on the purpose of the trial. Risks associated with this drug can be best managed through screening of trial candidates and close monitoring.

• Health Canada continues to closely monitor the safety and effectiveness of hydroxychloroquine and other drugs used in the treatment of COVID-19, and will take appropriate and timely action, including informing Canadians if and when any new health risks are identified.
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 STAKEHOLDER ENGAGEMENT

• Health Canada is actively engaging with stakeholders in the health product industry to proactively identify, track and provide support to sponsors of clinical trials for COVID-19.

• Health Canada recognizes that many stakeholders, health professionals and Canadians are looking for the latest information about health products for COVID-19. The department has created a new website for the health product industry, so they know how to apply for regulatory approval and who to contact for questions. We are also making sure information relevant to health professionals and Canadians is up-to-date on our website.
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.