CAR-T Therapy: Challenges for Implementation in Canada
In 2017, autologous chimeric antigen receptor (CAR) T-cell therapy, tisagenlecleucel (Kymriah®, Novartis), became the first gene therapy approved in the United States for acute lymphoblastic leukemia in children and young adults. In 2018, regulatory approval in the UK and Canada followed suit, approving Kymriah® for some patients with relapsing/refractory (r/r) hematological malignancies. These announcements were met with both fanfare and skepticism, due to the dramatic evidence of efficacy and limited patient data, respectively. More recently CADTH has completed an Optimal Use report for Kymriah®. The report confirmed clinical benefit while acknowledging the unique administrative, regulatory, and reimbursement challenges.
A coordinated national-level approach is essential for the coming deluge of CAR-T therapies, with targets including more than 40 cancers, and preclinical studies in infection, autoimmunity and allotransplantation. Timely collection and analysis of Real-World Data will inform best practices and refine indications to ensure cost-effectiveness and optimal outcomes. Here, we assess the uncertainties and challenges facing CAR-T therapy implementation in Canada.
Reimbursement Challenges
In Canada, regulatory approval does not guarantee access if the price of an emerging therapy is too high. The current pricing for a single dose of Kymriah® is $475,000 USD. Beyond the treatment itself, additional costs of administration include: for preparatory chemotherapy, leukapheresis and cell infusion, management of side-effects (occurring in nearly all tested individuals), and biologics to treat cytokine release syndrome (the most significant CAR-T toxicity occurring in about one-third of patients).
While a single CAR-T infusion may enable many cancer-free years for some individuals, nearly half of CAR-T recipients require additional stem-cell transplantation during remission at an estimated cost of $200,000 USD. As such, the true cost of CAR-T therapy is difficult to estimate and represents a substantial risk for payers.
While the price negotiations are underway in Canada, it will be interesting to see if a value-based agreement will be considered. In the US, Novartis offered outcomes-based pricing to designated clinical centers to cover all treated patients regardless of their insurance plan. In this scenario, Novartis only bills centers for pediatric and young adult patients who respond to CAR-T therapy at the end of the first-month post-infusion. Although this arrangement protects payers from failures in CAR-T manufacturing, studies have shown that up to 37% of the patients meeting response criteria at one-month relapse within a year.
Implementation of CAR-T Therapy in Canada
Delivering CAR-T therapy poses unique challenges, requiring new health system capacities and investments in infrastructure. A recent review of commercial CAR-T therapy by Memorial Sloan Kettering Cancer Center identified several essential tasks that are required for successful delivery, including: administrative infrastructure, manufacturing, standard operating procedures and post-infusion care. These tasks echo those outlined in CADTH’s Optimal Use report.
Conclusion
Despite many unknowns, CAR-T therapy is poised for implementation in Canada. For patients with previously intractable malignancies, CAR-T therapy represents hope. Realizing this hope in a real-world Canadian setting will require overcoming financial, regulatory, reimbursement and administrative barriers. CADTH’s Optimal Use report on Kymriah® provides a road-map to building the necessary infrastructures and capacities, and provinces will need to collaborate to ensure equitable and timely access for patients across Canada.
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Read more in our white paper for more details on CAR-T and the challenges for implementations in Canada.