Regulatory Decision Summary for Tepadina

CNS lymphoma is a very rare and incurable condition. The safety and efficacy evidence in support of Tepadina-containing high-dose chemotherapy (HDCT) consolidation regimen for the treatment of adult patients with CNS lymphoma stem from 18 published open-label, retrospective or prospective analyses.

The efficacy evidence provided in the submission represents a clinically meaningful and promising clinical benefit for CNS lymphoma patients. The expert opinion from a Canadian hematologist describing the clinical utility of Tepadina for the treatment of CNSL patients in Canada provided further support for the sought indication. Additionally, Health Canadas Scientific Advisory Committee on Oncology Therapies (SAC-OT) was consulted and considers the drug to represent a benefit to patients with CNS lymphoma.

The most common adverse event associated with high-dose Tepadina is profound myelosuppression (anemia, neutropenia and thrombocytopenia) observed in 100% of patients. Extramedullary toxicities often reported include infections, mucositis, neurotoxicity, gastrointestinal toxicity (stomatitis, nausea, vomiting and diarrhea) and skin toxicity (skin rash and alopecia). Serious adverse events observed in CNS lymphoma patients include infections (pneumonia), sepsis, hemorrhage, cerebrovascular event, pulmonary embolism, neurotoxicity, leukoencephalopathy, acute respiratory distress syndrome and Stevens-Johnson syndrome. All adverse events reported in CNS patients, uncertainties, as well as monitoring and management recommendations are adequately described in the Canadian Product Monograph.

The overall benefit-harm-uncertainty balance is considered positive for the use of Tepadina as part of a HDCT consolidation regimen with stem cell rescue for the treatment of adult patients with CNS lymphoma. Tepadina has therefore been granted market authorization under the Notice of Compliance with Conditions (NOC/c) guidance. The commitments to be fulfilled include a confirmatory study on long-term use of Tepadina as part of a high-dose chemotherapy regimen followed by hematopoietic stem cell transplantation (HSCT) in Canadian and American patients, and post market surveillance commitments including periodic submission of Periodic Benefit-Risk Evaluation Reports for NOC/c products (PBRER-Cs), as well as other measures in accordance with the NOC/c Guidance.