Regulatory Decision Summary for Blincyto

Authorization was based on data from a single-arm pivotal study, with supporting data from an exploratory study. In the pivotal study, patients (N=116) with Philadelphia chromosome negative B-precursor acute lymphoblastic leukemia (ALL) in first or second hematologic complete remission with minimal residual disease (MRD) greater than or equal to 0.1% received blinatumomab at a dose of 15 µg/m2/day continuous infusion for 28 days followed by a treatment-free period of 2 weeks, for up to 4 treatment cycles. The primary endpoint was the proportion of patients who achieved complete MRD response within one cycle of Blincyto treatment. Eighty-eight out of 113 (78%) patients achieved a complete MRD response after one cycle of treatment. The MRD complete response achieved at cycle 1 was sustainable, with a median duration of 17.3 months. The key secondary endpoint was hematologic relapse-free survival (RFS) after 18 months of follow-up, and was estimated to be 54% when censored at Hematopoietic Stem Cell Transplantation (HSCT) or post-Blincyto chemotherapy.

The safety profile for the adult MRD-positive ALL population is consistent with the known safety profile of blinatumomab in the treatment of relapsed/refractory ALL. Most identified serious risks such as cytokine release syndrome, infusion reaction, tumor lysis syndrome, neurological toxicity and serious infections can be managed with close monitoring, prophylactic medications, immediate treatment, and dose adjustment or discontinuation of Blincyto.

Overall, considering the high rate and durability of MRD response with Blincyto treatment, and the manageable safety profile, the benefit to risk ratio is considered favorable for the treatment of patients with B-precursor ALL, who are in hematologic complete remission and MRD positive. Health Canada granted authorization under the NOC/c policy for Blincyto for the treatment of patients with Philadelphia chromosome negative B-precursor ALL, in hematologic complete remission with MRD ≥ 0.1%. Conditions of authorization, include the requirement to submit the final reports from two ongoing Phase 3 trials to confirm the benefit of Blincyto in treatment of MRD-positive ALL, and to address uncertainties such as the impact of Blincyto on stem cell transplantation outcomes.