Abecma is the world's first marketed BCMA-directed CAR-T cell therapy.

January 20, 2022 / Bio Valley BIOON/--Bristol-Myers Squibb (BMS) recently announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved B cell maturation antigen (BCMA)-directed chimeric antigen receptors (CAR) T-cell therapy Abecma (idecabtagene vicleucel, ide-cel) for the treatment of adult patients with relapsed and refractory multiple myeloma (R/RMM) who have received at least 3 prior therapies (including immune modulators, proteasome inhibitors, anti-CD38 antibodies) and who experienced disease progression on the last line of therapy or relapsed after treatment.

Abecma is a first-in-class, BCMA-directed, personalized immune cell therapy. BCMA is a protein that is almost universally expressed on multiple myeloma cancer cells. As an anti-BCMACAR-T cell therapy, Abecma recognizes and binds to BCMA, resulting in the death of BCMA-expressing cells.

Abecma is the world's first BCMACAR-T cell therapy to receive regulatory approval, with approval in the US in March 2021 and the EU in August 2021. The launch of Abecma will provide R/RMM patients with a new, effective, and personalized treatment regimen that can achieve rapid, deep, and durable remission with only one infusion. In clinical studies, Abecma's safety has been well established in treated patients, with cytokine release syndrome (CRS) and neurotoxicity (NT) mostly low-grade, with predictable early onset, and rapid subsided.

The principle of Abecma is to chimerize the BCMA receptor on the patient's T cells. The preparation process is as follows: T cells are isolated from the blood of each patient, and the T cells are modified with a lentiviral vector encoding the BCMA antigen receptor. BCMA receptors are expressed on the surface of T cells. During treatment, MM patients are pretreated with 2 chemotherapy drugs (cyclophosphamide and fludarabine) to kill existing T cells in the patient, followed by an infusion of Abecma, which begins once the infusion is back into the patient Find and kill cells that express BCMA.

Abecma is part of a co-development, co-promotion and profit-sharing agreement between Bristol-Myers Squibb and Bluebird Bio to jointly develop and commercialize Abecma in the U.S. market. Bristol-Myers Squibb will be solely responsible for the production and commercialization of Abecma outside the United States.

The Japan approval is based on data from a global Phase 2 clinical study BB2121-MM-001 in Japan, the United States, the European Union and Canada, and a Phase 1 study CRB-401 in the United States.

In BB2121-MM-001, 128 non-Japanese patients and 9 Japanese patients received ide-cel infusion. RESULTS: Among 128 non-Japanese patients (target doses of 150, 300, 450x10E6 CAR-positive T cells), the overall response rate (ORR) was 73.4% (95% CI: 65.8-81.1), with a 50% threshold compared with statistical significance. In 9 Japanese patients (target dose of 450x10E6 CAR-positive T cells), the ORR was 88.9% (95%CI: 51.8-99.7).

In the CRB-401 trial (21 patients dose escalation: target dose of 50, 150, 450, or 800x10E6; 41 patients dose expansion: target dose of 150 or 450x10E6), ORR was 74.2% (95%) in 62 patients CI: 61.5-84.5), ORR was 84.2% (95% CI: 68.7-94.0) in 38 patients (target dose 450x10E6).

In the BB2121-MM-001 trial, 134 of 137 patients (including 9 Japanese patients) who received ide-cel had adverse reactions. Adverse reactions included cytokine release syndrome (84.7%), neutropenia (59.9%), thrombocytopenia (45.3%), anemia (38.0%), leukopenia (27.7%), fatigue (16.1%) ), lymphopenia (14.6%), hypogammaglobulinemia (11.7%), and pyrexia (10.2%) (cumulative to approval).

In the CRB-401 trial, 55 of 62 patients treated with ide-cel experienced adverse reactions. Adverse reactions included cytokine release syndrome (75.8%), neutropenia (41.9%), thrombocytopenia (40.3%), anemia (38.7%), fatigue (32.3%), leukopenia (27.4%) ), lymphopenia (16.1%), nausea (14.5%), headache (14.5%), hypophosphatemia (12.9%), and upper respiratory tract infection (11.3%) (cumulative to approval). (Bioon.com)