Gene therapy is here: Now what?

By Sarah Garland

Genes are the building blocks of life on earth, and genetic material provide the set of instructions that makes us who we are. However, abnormal genes can be the cause of disease and illness; and when we get sick, the thought that we can manipulate genetic material as a treatment for illness seems like the stuff of science fiction. Gene therapy can be defined as a set of strategies that change the behaviour of an individual’s genes, or repair abnormal genes. This can involve immunotherapies that modify an individual’s cells, or regenerative medicine that uses modified cells or tissues to treat an illness.

Gene therapy is an area of therapeutics – the field of medicine focused on the treatment of disease – with the goal of curing or significantly improving the management of diseases with few or no treatment options. These are typically treatments for people with severe, hard-to-treat illness. While gene therapy has been an active area of research for the past few decades, the approval of gene therapy products for marketing has been a recent development (e.g., 2015 for approval in the United States). A 2017 brief by the Massachusetts Institute of Technology’s New Drug Development Paradigms Initiative predicted that by the end of 2022, 40 new gene therapies would be approved for use, with the majority treating cancers and diseases that affect very few people (i.e., orphan diseases or extremely rare diseases).

One area of particular focus has been gene therapies for cancers that do not respond well to conventional treatment (e.g., chemotherapies and radiation). Cancers of the blood and lymphatic system show promise as some gene therapies involve manipulating immune cells outside of the body and transferring them back to the patient. Chimeric antigen receptor T-cell therapy – or CAR T-cell therapy – is a type of gene therapy that does just that. CAR T cells are engineered by removing T cells (immune cells) from the blood, modifying them in a laboratory to recognize antigens (protein labels) commonly expressed on cancer cells, and reinjecting them into the patient, where they multiply and attack diseased cells.

While there is a lot of excitement about gene therapy, there are also some considerations for their implementation into our health system. To help guide decisions about gene therapy, and specifically CAR T-cell therapy, decision-makers and the healthcare community turned to CADTH — an independent agency that finds, assesses, and summarizes the research on drugs, medical devices, tests, and procedures — to find out what the evidence says. CADTH undertook an environmental scan (Gene Therapy: International Regulatory and Health Technology Assessment (HTA) Activities and Reimbursement Status) and a horizon scan (Gene Therapy: An Overview of Approved and Pipeline Technologies).

The environmental scan and horizon scan reports paint a complex picture of gene therapies in Canada, and internationally. There is widespread variation in the definition of gene therapy used by regulatory bodies, and by reimbursement bodies. These reports also highlighted specific areas for consideration, including the adequacy of evidence for decision-making, the cost of treatment, and the health system requirements that need to be in place to provide gene therapies.

Since these technologies are so new, and are sometimes regulated through accelerated reviews, they may reach the market with limited evidence on how well they work and without long-term data on their safety and effectiveness. This uncertainty could mean that certain regions (i.e., provinces or countries) make contradictory decisions about the adoption of gene therapies until initial findings are confirmed. Additionally, gene therapies tend to be quite expensive, with listed costs ranging from US$65,000 to greater than US$1 million. This makes decisions about insurance and reimbursement additionally complex, and could create a barrier for the provision of gene therapies. In terms of providing gene therapies, there may be special requirements for manufacturing facilities, care facilities, clinician training, and follow-up care for patients.

CADTH is also currently reviewing two CAR T-cell therapies: tisagenlecleucel and axicabtagene ciloleucel. Tisagenlecleucel is a CAR T-cell therapy for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) and children and adolescents with relapsed or refractory acute lymphoblastic leukemia (r/r ALL). Axicabtagene ciloleucel is a treatment for adult patients with relapsed or refractory large B-cell lymphoma. This includes DLBCL, high grade B-cell lymphoma, and sub-types of DLBCL (e.g., primary mediastinal large B-cell lymphoma and DLBCL arising from follicular lymphoma).

For both tisagnelecleucel and axicabtagene ciloleucel, CADTH is undertaking Optimal Use projects to assess the clinical impact, cost-effectiveness, and implementation considerations including patient and caregiver perspectives and experiences, ethical considerations, and other considerations such as facilities for the administration of CAR T-cell therapy, therapy eligibility, travel requirements, and resource costs associated with the provision of these therapies in Canada.

The area of gene therapy is complex and ever changing. CADTH reviews are here to help healthcare decision-makers and provide much needed evidence.

To learn more about CAR T-cell reviews at CADTH, visit:

To learn more about CADTH, visit, follow us on Twitter: @CADTH_ACMTS, or talk to our Liaison Officer in your region:

Sarah Garland is a Knowledge Mobilization Officer at CADTH.