Regulatory Decision Summary for Kymriah
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.
Type of submission:
What was the purpose of this submission?
The purpose of this submission was to seek market authorization for Kymriah (tisagenlecleucel), a CD19-directed genetically modified autologous T-cell immunocellular therapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are ineligible for or relapse after autologous stem cell transplant.
After evaluation of the submitted data package, Health Canada authorized Kymriah for the following indication:
- Kymriah (tisagenlecleucel) is a CD19-directed genetically modified autologous T-cell immunocellular therapy indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma.
Why was the decision issued?
The authorization of Kymriah was based on the results of JULIET, an international, multi-centre, single-arm trial. Patients (n = 106) with relapsed refractory DLBCL who had received at least 2 prior systemic treatments received a single Kymriah infusion.
The primary efficacy endpoint was the Overall Response Rate as assessed by an independent review committee applying the Lugano response criteria for malignant lymphomas. The rates of complete response and partial response as well as the duration of response were key secondary endpoints. Response was evaluable for 68 infused patients in whom substantial rates of overall response and complete response were observed. Complete responses were demonstrated to be durable.
The most common adverse reactions (ADRs) reported in at least 20% of patients were cytokine release syndrome (CRS), infections, fever, diarrhea, nausea, hypotension, fatigue, headache, and hypokalemia. The most important identified risks of Kymriah treatment are CRS and neurological toxicity, which may occur in the setting of CRS. The product monograph gives specific details on how to monitor for and manage CRS arising after Kymriah infusion. Prolonged cytopenias are also of concern and may put patients at increased risk for infection. Additional risk mitigation measures, put in place by the sponsor, include the implementation of controlled distribution and educational programs, which will serve to ensure that health care practitioners are trained in the safe use of Kymriah and that facilities are prepared to manage adverse reactions as they arise.
Given the substantial evidence of efficacy observed in a population of patients with a high unmet medical need, the risks are considered acceptable when tisagenlecleucel is administered under the conditions described in the product monograph (PM). Therefore, the overall benefit-risk assessment is favourable.
The recommended dose of Kymriah is 0.6 - 6 x 108 viable CAR-T cells administered as a single intravenous infusion. View the PM for details.
Health Canada granted this application priority review in accordance with the priority review policy.
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.