Regulatory Decision Summary for Breyanzi

The purpose of the Supplement to a New Drug Submission (SNDS) was to add a new indication for Breyanzi for the treatment of adult patients with large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma (PMBCL), high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma, who are refractory or have relapsed.

After evaluation of the submitted data package, Health Canada authorized Breyanzi for the following indication: for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma (HGBCL), and DLBCL arising from follicular lymphoma, who have refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy, and who are candidates for autologous hematopoietic stem cell transplant (HSCT).

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

Authorization was based on an international, multi-centre, randomized, active-controlled Phase 3 clinical trial, BCM-003 (TRANSFORM). Adult patients (n = 184) with large B-cell lymphoma (including diffuse large B-cell lymphoma [DLBCL] not otherwise specified [NOS], primary mediastinal large B-cell lymphoma [PMBCL], high-grade B-cell lymphoma [HGBCL], and DLBCL arising from follicular lymphoma [FL]), who had refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy, and who were candidates for autologous hematopoietic stem cell transplant (HSCT), were randomized 1:1 to receive either Breyanzi or a platinum-containing salvage chemoimmunotherapy followed by autologous hematopoietic stem cell transplant (HSCT).

The primary efficacy endpoint was event-free survival (EFS). The study demonstrated a statistically significant improvement in EFS in the Breyanzi arm versus the salvage chemoimmunotherapy arm, with a hazard ratio of 0.349, indicating that patients treated with Breyanzi had a 65.1% reduction in the risk of experiencing EFS events. The median EFS was 10.1 months in the Breyanzi arm compared to 2.3 months in the salvage chemoimmunotherapy arm.

The most common adverse reactions reported in at least 20% of patients in the Breyanzi arm were neutropenia, anemia, thrombocytopenia, pyrexia, cytokine release syndrome (CRS), headache, fatigue, nausea, lymphopenia, dizziness, and constipation. The most common serious adverse reactions reported in 2 or more patients were CRS, neutropenia, pyrexia, thrombocytopenia, febrile neutropenia, pulmonary embolism, headache, aphasia, and COVID-19 infection. The safety finding in Study BCM-003 was consistent with previous observations.

Overall, the benefit/risk profile of Breyanzi is considered favourable for the treatment of adult patients with DLBCL NOS, PMBCL, HGBCL, and DLBCL arising from follicular lymphoma, who have refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy, and who are candidates for autologous hematopoietic stem cell transplant (HSCT).

The recommended dose for the new indication is the same as the currently authorized dose: a single-dose, one-time treatment that contains 60 x 10⁶ to 120 × 10⁶ CAR-positive viable T cells (consisting of CD4 and CD8 components at a ratio range from 0.8 to 1.2).

An updated Risk Management Plan (RMP) for Breyanzi was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for Breyanzi has demonstrated that the drug substances and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and Product Monograph were considered acceptable.

A Notice of Compliance (NOC) was recommended.

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