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?
This New Drug Submission (NDS) was filed to seek market authorization for Kymriah (tisagenlecleucel), a CD19-directed genetically modified autologous T-cell immunocellular therapy, for the treatment of pediatric and young adult patients 3 to 25 years with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
After evaluation of the submitted data package, Health Canada (HC) authorized Kymriah for the following indication:
- Kymriah (tisagenlecleucel) is a CD19-directed genetically modified autologous T-cell immunocellular therapy indicated for the treatment of pediatric and young adult patients 3 to 25 years with B-cell acute lymphoblastic leukemia (ALL) who are refractory, have relapsed after allogeneic stem cell transplant (SCT) or are otherwise ineligible for SCT, or have experienced second or later relapse.
Why was the decision issued?
Authorization was based primarily on the results of two international, multi-centre, single-arm trials. Patients in each trial (pivotal trial B2202, n = 75 and supportive trial B2205J, n = 29) were pediatric and young adult patients age 3-25 with refractory or relapsed (r/r) B-cell acute lymphoblastic leukemia (ALL). Each patient received a single infusion of Kymriah. The primary efficacy endpoint of each trial was the overall remission rate (ORR), defined as the number of complete remissions. The key secondary endpoint was the duration of remissions.
In both the pivotal trial and supportive trial, the ORR was substantially better than reported for currently authorized chemotherapy drugs. In addition, a clinically meaningful proportion of these remissions have been found to be substantially more durable.
The most common adverse reactions (ADRs) suspected to be study drug related in at least 20% of patients in both studies were cytokine release syndrome (CRS), hypogammaglobulinaemia, febrile neutropenia, hypotension, and pyrexia, and decreased appetite. Adverse neurological events occurred during CRS in the majority of affected patients. In about half of patients experiencing CRS the ADR was severe and required intensive care unit admission. Specific details for monitoring and managing CRS developing after Kymriah infusion are provided in the product monograph. Given the high risk of serious ADRs associated with Kymriah therapy, administration of therapy is restricted to facilities that are staffed by health care professionals well-trained and experienced in managing patients undergoing this therapy and who have participated in educational programs focusing on the monitoring and management of such ADRs.
Balancing the benefits and risks of Kymriah therapy in this population of patients whose ALL is refractory to, or has relapsed after, prior curative therapy, the risks are considered acceptable when Kymriah is administered in the clinical setting described in the product monograph (PM). Under such conditions, the overall benefit-risk assessment is considered favourable.
The recommended dose of Kymriah for indication is 0.2 to 5.0 x 106 CAR-positive viable T cells/kg body weight for patients who weigh 50 kg or less and 0.1 to 2.5 x 108 CAR-positive viable T cells for patient who weigh more than 50 kg. Further details are available in the PM.
Health Canada granted this application priority review in accordance with the priority review policy.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.
Related Drug Products
| Product name | DIN | Company name | Active ingredient(s) & strength |
|---|---|---|---|
| KYMRIAH | 02480514 | NOVARTIS PHARMACEUTICALS CANADA INC | TISAGENLECLEUCEL 600000000 CELLS |