Regulatory Decision Summary for Blincyto

The Supplement to a New Drug Submission (SNDS) for Blincyto was classified as a Project Orbis Type A submission and Health Canada collaborated with the United States Food and Drug Administration (FDA), Swissmedic (SMC), Singapore’s Health Sciences Authority (HSA), United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) and the Brazilian Health Regulatory Agency (ANVISA) for the review.

The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

The sponsor filed the submission seeking a Notice of Compliance for Blincyto for the treatment of B-cell precursor Acute Lymphoblastic Leukemia in the consolidation phase of multiphase chemotherapy. After evaluation of the submitted data package, Health Canada authorized Blincyto for the treatment of patients with Philadelphia chromosome-negative CD19 positive B-cell precursor acute lymphoblastic leukemia in the consolidation phase of multiphase chemotherapy.

Previously authorized indications include the treatment of:

• Patients with Philadelphia chromosome-negative CD19 positive B-cell precursor ALL in first or second hematologic complete remission with minimal residual disease (MRD) greater than or equal to 0.1%.

• Adult patients with relapsed or refractory B‑cell precursor ALL.

• Pediatric patients with Philadelphia chromosome-negative relapsed or refractory B‑cell precursor ALL.

Authorization was based on 2 pivotal clinical studies in combination with supporting trials. Additional information supported extrapolation to allow for the use of blinatumomab, as a part of consolidation treatment, in newly diagnosed pediatric Philadelphia chromosome-negative B-ALL, which included scientific rationale and pharmacokinetic analyses as well as safety data collected in pediatric patients as young as 1 year of age.

The pivotal efficacy studies investigated Blincyto, used in the consolidation phase of multiphase chemotherapy in either newly diagnosed adults (study E1910) or first relapse pediatric patients (study 20120215). The adult study randomized 224 patients (1:1) to receive Blincyto + standard of care (SOC) chemotherapy vs. SOC chemotherapy alone in consolidation while the pediatric study randomized 111 patients to receive Blincyto vs. SOC chemotherapy. In both studies a significant improvement in Overall Survival was observed with the addition of Blincyto to the consolidation phase of treatment.

In a pooled analysis, the most common adverse events (≥40% of patients receiving Blincyto alone or Blincyto + chemotherapy) experienced by patients during consolidation were pyrexia, anemia, white blood cell count decreased, alanine aminotransferase increased, neutrophil count decreased, headache, and platelet count decreased. The most common grade ≥3 adverse events (≥15% of patients receiving Blincyto alone or Blincyto + chemotherapy) were neutrophil count decreased, lymphocyte count decreased, white blood cell count decreased, anemia, platelet count decreased, alanine aminotransferase increased, febrile neutropenia, and stomatitis. Considering only patients who received Blincyto alone in consolidation, the most common grade ≥3 adverse events (≥10%) were neutrophil count decreased, lymphocyte count decreased, white blood cell count decreased and anemia.

Important adverse events of interest for Blincyto are neurologic events including immune effector-cell associated neurotoxicity (ICANS). The risks of these events and others, including infusion reactions, medications errors, tumour lysis syndrome, neutropenia, pancreatitis and febrile neutropenia are clearly communicated within the Product Monograph with recommended options for management, which may include supportive care, dose interruption or treatment discontinuation.

Considering the benefits of adding Blincyto to the consolidation phase of treatment, which include significant improvements in survival, observed in newly diagnosed adult B-ALL (Ph-negative) and in first-relapsed pediatric B-ALL (Ph-negative), and considering a safety profile that is well established with appropriate labelling to mitigate risk, the benefit-risk of Blincyto is favourable for the indication: Blincyto is indicated for the treatment of patients with Philadelphia chromosome-negative CD19 positive B-cell precursor acute lymphoblastic leukemia (ALL) in the consolidation phase of multiphase chemotherapy.

The recommended doses for Blincyto in the consolidation phase of treatment are the same as the currently authorized doses.

A Notice of Compliance (NOC) was recommended.

For more information on the benefits and risks of Blincyto, refer to the product monograph approved by Health Canada and available through the Drug Product Database.