FDA Grants Priority Review to Expand Indication for Bristol Myers Squibb’s Breyanzi in CLL, SLL

The FDA has accepted a supplemental Biologics License Application (sBLA) and granted Priority Review status to expand the current indication for lisocabtagene maraleucel (Breyanzi).

The sBLA seeks to include the treatment of adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who were previously administered a Bruton tyrosine kinase inhibitor (BTKi) and B-cell lymphoma 2 inhibitor (BCL2i). Breyanzi is a CD19-directed chimeric antigen receptor (CAR) T-cell therapy with a 4-1BB costimulatory domain, which enhances the expansion and persistence of the CAR T cells.

“Currently, there is no standard of care for people living with relapsed or refractory CLL or SLL after treatment with BTKi- and BCL2i-based regimens, leaving a critical unmet need for a treatment option that provides deep and lasting responses,” Anne Kerber, senior vice president and head, Late Clinical Development, Hematology, Oncology, Cell Therapy (HOCT), Bristol Myers Squibb, said in a press release. “This FDA acceptance brings us one step closer to offering these patients, for the first time, a personalized, T-cell based treatment option. We’re proud to further our commitment to bring the potential of CAR T-cell therapy to more patients, building on Breyanzi’s foundation as a differentiated treatment option that has shown clinical benefit in the broadest array of B-cell malignancies.”

The FDA has already approved Breyanzi to treat adults with large B-cell lymphoma (LBCL), including diffuse LBCL that is not otherwise specified; high-grade B-cell lymphoma; primary mediastinal LBCL; and patients with follicular lymphoma grade 3B whose disease is refractory to first-line chemoimmunotherapy or who relapse within 12 months of first-line chemoimmunotherapy, or disease that is refractory to first-line chemoimmunotherapy or relapse following first-line chemoimmunotherapy and who are not eligible for hematopoietic stem cell transplant because of comorbidities, age, or relapsed or refractory disease following two or more lines of systemic therapy. Breyanzi is not indicated to treat primary central nervous system lymphoma. The drug is made by extracting the patient’s own T cells to genetically reengineer them to become CAR T cells, which are subsequently infused as a one-time treatment.

The FDA accepted the sBLA based on findings from the pivotal Phase 1/2, open-label, single-arm, multicenter TRANSCEND CLL 004 (NCT03331198) trial. This was the first pivotal multicenter study that demonstrated a clinical benefit with a CD19-directed CAR T-cell therapy among patients with relapsed or refractory CLL whose disease progressed after treatment with a BTKi and BCL2i.

In the Phase 1 dose escalation part of the study, investigators evaluated the safety and recommended dosage for the Phase 2 expansion portion, which analyzed Breyanzi at the dose determined by the Phase 1 monotherapy cohort. The primary endpoint of the Phase 2 part of TRANSCEND CLL 004 was complete response rate, which includes complete remission with incomplete bone marrow recovery.

CLL, one of the most common types of leukemia in adults, occurs when too many blood stem cells in the bone marrow become abnormal lymphocytes. This causes difficulty for the abnormal cells to effectively fight infections. As the amount of abnormal cells increases, healthy white blood cells, red blood cells, and platelets have less room to launch an effective immune response. SLL is similar to CLL; however, these cancer cells are mostly found in the lymph nodes.

The sBLA for Breyanzi was assigned a Prescription Drug User Fee Act goal date of March 14, 2024.

Reference

U.S. Food and Drug Administration Accepts for Priority Review Bristol Myers Squibb’s Application for Breyanzi (lisocabtagene maraleucel)for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). Bristol Myers Squibb. November 9, 2023. Accessed November 10, 2023. https://news.bms.com/news/corporate-financial/2023/U.S.-Food-and-Drug-Administration-Accepts-for-Priority-Review-Bristol-Myers-Squibbs-Application-for-Breyanzi-lisocabtagene-maraleucelfor-Relapsed-or-Refractory-Chronic-Lymphocytic-Leukemia-CLL-or-Small-Lymphocytic-Lymphoma-SLL/default.aspx