Bristol Myers Squibb Receives Approval for Abecma (idecabtagene vicleucel), the First BCMA-Directed CAR T Cell Therapy for Relapsed/Refractory Multiple Myeloma in Japan

News on January 20, 2022 /BioValleyBIOON/ -- Bristol-Myers Squibb (BMS) recently announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved the B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy Abecma (idecabtagene vicleucel, ide-cel) for the treatment of adult patients with relapsed and refractory multiple myeloma (R/R MM). Specifically, it is indicated for R/R MM adult patients who have previously received at least three prior lines of therapy (including immunomodulatory agents, proteasome inhibitors, anti-CD38 antibodies) and have experienced disease progression on or after the last therapy.

Abecma is a first-in-class, BCMA-directed, personalized cellular immunotherapy. BCMA is a protein that is almost universally expressed on multiple myeloma cancer cells. As an anti-BCMA CAR-T cell therapy, Abecma identifies and binds to BCMA, leading to the death of BCMA-expressing cells.

Abecma is the world's first BCMA CAR-T cell therapy to receive regulatory approval.Approved in the United States in March 2021 and in the European Union in August 2021. The launch of Abecma will provide patients with R/R MM a new, effective, personalized treatment option that can achieve rapid, deep, and durable remission with just one infusion. In clinical studies, the safety of Abecma has been well demonstrated in treated patients, with most cases of cytokine release syndrome (CRS) and neurotoxicity (NT) being low-grade, having predictable early onset, and resolving quickly.

The principle of Abecma is to chimerically express the BCMA receptor on the patient's T cells., the preparation process is: T cells are isolated from the blood of each patient, and lentiviruses encoding the BCMA antigen receptor are used.VectorT cells are modified to express the BCMA receptor on their surface. During treatment, MM patients first receive pre-treatment with two chemotherapy drugs (cyclophosphamide and fludarabine) to eliminate existing T cells in the patient’s body, followed by infusion of Abecma. Once infused back into the patient, Abecma begins seeking and destroying cells that express BCMA.

Abecma is part of a co-development, co-promotion, and profit-sharing agreement between Bristol-Myers Squibb and Bluebird Bio. The two parties 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.

This approval in Japan was based on data from the global Phase 2 clinical study BB2121-MM-001 conducted in Japan, the United States, the European Union, and Canada, as well as from the Phase 1 study CRB-401 conducted in the United States.

In BB2121-MM-001, 128 non-Japanese patients and 9 Japanese patients received ide-cel infusion treatment. The results showed that among the 128 non-Japanese patients (target dose was 150, 300, 450 x 10E6 CAR-positive T cells),The overall response rate (ORR) was 73.4% (95% CI: 65.8-81.1)., which is statistically significant compared to the 50% threshold. In nine Japanese patients (target dose of 450 x 10E6 CAR-positive T cells), the ORR was 88.9% (95% CI: 51.8-99.7).

In the CRB-401 trial (dose escalation in 21 patients: target dose of 50, 150, 450, or 800 x 10E6; dose expansion in 41 patients: target dose of 150 or 450 x 10E6), the ORR was 74.2% (95% CI: 61.5-84.5) among 62 patients and 84.2% (95% CI: 68.7-94.0) among 38 patients (target dose of 450 x 10E6).

In the BB2121-MM-001 trial, 134 of the 137 patients (including 9 Japanese patients) who received ide-cel treatment experienced adverse reactions.Adverse ReactionsIncluding cytokine release syndrome (84.7%), neutropenia (59.9%), thrombocytopenia (45.3%),Anemia(38.0%), leukopenia (27.7%), fatigue (16.1%), lymphocytopenia (14.6%), hypogammaglobulinemia (11.7%), and fever (10.2%) (cumulative up to approval).

In the CRB-401 trial, 55 of the 62 patients treated with ide-cel experienced adverse reactions.Adverse ReactionsIncluding 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)

Source of the original text:Bristol Myers Squibb Receives Approval for Abecma (idecabtagene vicleucel), the First CAR T Therapy Approved for the Treatment of Multiple Myeloma in Japan