Regulatory Decision Summary for Kymriah
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
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What was the purpose of this submission?
The purpose of this Supplement to a New Drug Submission (SNDS) was to gain market authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for Kymriah, submitted by Novartis Pharmaceuticals Canada Inc.
This Supplement to a New Drug Submission was filed to obtain market authorization for:
“Kymriah (tisagenlecleucel) is a CD19-directed genetically modified autologous T-cell immunocellular therapy indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of therapy.”
Upon review, the approved indication was:
“Kymriah (tisagenlecleucel) is a CD19-directed genetically modified autologous T-cell immunocellular therapy indicated for the treatment of adult patients with relapsed or refractory grade 1, 2, or 3a follicular lymphoma (FL) after two or more lines of systemic therapy.”
The Supplement to a New Drug Submission for Kymriah was filed under the Priority Review Policy.
The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.
Kymriah is currently authorized in Canada and is available as tisagenlecleucel cell suspension in patient-specific single infusion bags containing 1.2 x 106 – 6.0 x 108 chimeric antigen receptor (CAR)-positive T cells.
Why was the decision issued?
The authorization was based on one pivotal clinical study, E2202, which was a single arm, Phase II, open-label, multicenter study of Kymriah in patients with relapsed or refractory follicular lymphoma (r/r FL). Patients with r/r FL (n = 94) received a single-infusion of tisagenlecleucel.
The study met its primary endpoint by establishing a significant Complete Response (CR) rate of 66%, (95% Confidence Interval (CI): 56, 75) in the set of patients who had measurable disease prior to infusion (n = 62/94). The median follow-up time after infusion was 11 months. The Overall Response Rate (ORR) was 86% (95% CI: 78, 92). The responses were durable and the median duration for patients achieving an overall response was not estimable at the time set for the primary analysis. Of the 62 patients who achieved a CR, 12 patients initially had a partial response (PR).
There are important identified risks associated with Kymriah treatment. Notably, cytokine release syndrome (CRS), infections, and neurological toxicities. Careful monitoring for CRS and/or neurological toxicities is warranted and the management of these adverse events includes the use of corticosteroids and tocilizumab. Infections can be managed by healthcare professionals as needed through antibiotic treatments. Kymriah is known to increase the risk of prolonged cytopenias in patients. However, the majority of cytopenias do resolve over time and patients can receive specific replacement treatments if required.
Treatment with Kymriah has resulted in high response rates, including a majority of complete responses that have been demonstrated as relatively durable in the study. Toxicities associated with infusion of Kymriah are manageable through treatment in specialised cancer centres, close monitoring, and the use of corticosteroids and anti-IL6 monoclonal antibodies. Based on the complete analysis of the data, the benefit of Kymriah in treating patients with r/r FL as indicated is considered to outweigh the treatment risk. Confirmation of the benefits in a randomized, controlled trial of Kymriah compared to investigator’s choice of treatment consistent with the standard of care in patients with r/r FL is a condition of authorization.
An updated Risk Management Plan (RMP) for Kymriah was reviewed by Health Canada and considered acceptable.
Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.
Overall, the anticipated benefits of Kymriah are expected to outweigh the potential risks when used under the conditions of use recommended in the approved Product Monograph.
For further details about Kymriah, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.
Decision issued
Authorized; issued a Notice of Compliance (NOC) in accordance with the Food and Drug Regulations with Conditions Guidance.