IP monitor: Gene therapy products in Canada: regulation, IP and emerging issues

In recent years, the incredible promise of gene therapy has become a reality as multiple gene therapy products have come to market.  Here we provide an overview of how commercial gene therapy products are regulated and protected in Canada.  We also identify emerging issues affecting these products.

Canadian landscape for gene therapy

In Canada, 10 gene therapy products have been approved for marketing (see Table 1 below).  These products can be divided into two groups: (i) six CAR-T therapies for treating blood cancers; and (ii) four AAV-based therapies for restoring gene function.  In brief:

• CAR-T therapy: This gene therapy product is a suspension of a cancer patient’s own genetically modified T-cells.  The suspension is made by collecting T-cells from the patient’s blood and transforming them with a gene encoding a chimeric antigen receptor (CAR).  The CAR binds a protein (e.g., CD19, BCMA) on the surface of cancer cells.  The transformed T-cells are infused back into the patient’s body, where the CAR directs the T-cells to bind to and attack the cancer cells.
• AAV-based therapy:  This gene therapy product is an adeno-associated viral (AAV) vector containing a human gene (e.g., a gene that is not functioning properly in a patient).  The product is infused into the patient and the vector enters target cells, where its DNA persists episomally (i.e., not integrated into the genome) and restores gene function.

Regulation of gene therapy products in Canada

Canada does not have a distinct legislative framework for gene therapy products.  These products are subject to the same regulatory provisions as other drug products under the Food and Drugs Act and Food and Drug Regulations. To sell a gene therapy product in Canada, the sponsor must file a new drug submission with Health Canada.  If approved, the sponsor will receive a drug identification number and a notice of compliance (NOC).

Health Canada classifies gene therapy products as biologic drugs under Schedule D of the Food and Drug Regulations. They are reviewed by Health Canada’s Biologic and Radiopharmaceutical Drugs Directorate under guidelines for biologic drugs.

Gene therapy products are often evaluated in small patient populations and without traditional phase 3 clinical trials.  As such, they are often candidates for Health Canada’s Notice of Compliance with Conditions (NOC/c) pathway, in which drugs showing promising evidence of effectiveness for serious, life-threatening, or severely debilitating diseases can be approved subject to the drug’s sponsor agreeing to conduct further clinical trials.¹ The NOC/c pathway is also expedited relative to the traditional review process.  Most of the gene therapy products approved in Canada to date have been with an NOC/c.  

Gene therapy products may also be subject to other areas of Canadian regulation, including under the Assisted Human Reproduction Act and the New Substances Notification Regulations (Organisms).²

Intellectual property and gene therapy products in Canada 

Data protection: Gene therapy products are generally eligible for eight years of data protection market exclusivity under section C.08.004.1 of the Food and Drug Regulations.  A new drug is eligible for data protection if it is an “innovative drug,” meaning it contains a medicinal ingredient not previously approved in Canada.  While a new drug is under data protection, a generic or biosimilar drug manufacturer cannot rely upon the innovator’s data (e.g., clinical trial results) to obtain an NOC. 

Patent protection: Gene therapy products are patentable in Canada and subject to the same legislation as other patented products.  Of note:  

• Linkage regime:  The Patented Medicines (Notice of Compliance) Regulations require generic and biosimilar manufacturers to address the innovator’s listed patents on the Patent Register before they can receive an NOC.  In this way, an innovator’s patent rights are linked to regulatory approval of follow-on products.  Notably, five of the 10 approved gene therapy products in Canada have patents listed on the Patent Register.
• Extended patent terms:  A Certificate of Supplementary Protection (CSP) can provide up to two years of additional patent-like protection for drugs containing a new medicinal ingredient. To date, CSPs have been granted for two patents related to gene therapy products.  In addition, no later than January 1, 2025, Canada will implement a system of general patent term adjustment (PTA) to compensate patentees for unreasonable delays by the Patent Office in issuing a patent.  However, if a patent has a CSP and an additional PTA term, the two extensions will run concurrently (see our bulletin with the latest on PTA in Canada here).
• Price review: The Patented Medicine Prices Review Board (PMPRB) reviews the prices of patented medicines to ensure they are not sold at “excessive” prices. Patentees must identify relevant patents for the PMPRB and file certain pricing and sales information about their patented drugs. 

Patent litigation: Canada’s first litigation concerning a gene therapy patent started in October 2022. The litigation concerns the validity of certain claims in Canadian Patent No. 2,737,094 (titled “Factor IX Polypeptide Mutant, its Uses and a Method for its Production”).  The plaintiffs are represented by Norton Rose Fulbright Canada LLP.

Emerging issues for gene therapy products in Canada

Issues to keep an eye on in gene therapy in Canada include: 

• CRISPR:  Products employing CRISPR-based gene editing technology have not yet entered the Canadian market.  In addition, the patent disputes in Europe and the United States over the foundational CRISPR technology have not (yet) come before the Canadian courts.  
• Market access:  In recognition of the unique reimbursement challenges faced by these highly specialized therapies, one of Canada’s health technology assessment authorities has established a special review process for cell and gene therapies.³ However, Canada’s market access regime is in flux and the changes may impact – in positive or negative ways – market access to gene therapy products.  The changes include a new national strategy for rare diseases (see here), a new Canadian Drug Agency to improve coordination across the public funding system (see here), a new temporary access process for drugs approved via the NOC/c pathway (see here), and the possible expansion of a newly introduced system of national pharmacare (see here).
• PMPRB:  The PMPRB has been operating without a full set of drug pricing guidelines since July 1, 2022. The PMPRB has been consulting on new guidelines, which it has indicated it intends to finalize by the end of 2024 (see here).  How those guidelines will affect the pricing of patented gene therapy products remains to be seen. 

For more information on these and other legal and regulatory developments in Canadian pharma and biotech, please contact the authors and subscribe to our Pharma in Brief newsletter.