Bristol Myers Squibb and bluebird bio Announce FDA Approval of Abecma (idecabtagene vicleucel), the World’s First Anti-BCMA CAR T Cell Therapy for Relapsed or Refractory Multiple Myeloma

March 27, 2021/Bio ValleyBIOON/--Bristol-Myers Squibb (BMS) and its partner Bluebird Bio recently jointly announced that the U.S. Food and Drug Administration (FDA) has approved Abecma (idecabtagene vicleucel, ide-cel), a B-cell maturation antigen (anti-BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy for the treatment of adult patients with relapsed/refractory multiple myeloma (R/R MM), specifically those who have received four or more prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody. The approval of Abecma provides a new, effective, and personalized treatment option for these patients,Rapid, profound, and durable relief can be achieved with just a single infusion.

Abecma is a first-in-class, BCMA-directed, individualized immunocellular therapy administered as a single infusion for the treatment of patients with multiple myeloma who have received three prior classes of therapy. The recommended dose is 300–460 × 10⁶ CAR-positive T cells. BCMA is a protein expressed on nearly all multiple myeloma cancer cells. As an anti-BCMA CAR-T cell therapy, Abecma recognizes and binds to BCMA, leading to the death of BCMA-expressing cells.

It is particularly worth mentioning that,Abecma is the world’s first regulatory-approved BCMA-directed CAR-T cell therapy., and it is also the fifth CAR-T cell therapy approved by the U.S. FDA. In early February this year, Bristol-Myers Squibb's CD19 CAR-T cell therapy Breyanzi (lisocabtagene maraleucel, liso-cel) receivedFDAApproved for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (R/R LBCL).

The approval of Abecma has made Bristol-Myers Squibb the first pharmaceutical company to simultaneously hold two CAR-T cell therapies targeting CD19 and BCMA. Abecma was approved through the Priority Review program and is currently undergoing accelerated assessment by the European Medicines Agency (EMA). In the United States and the European Union, Abecma has been granted Breakthrough Therapy Designation (BTD) and PRIME (PRIority MEdicines) status, respectively.

Despite advances in the treatment of multiple myeloma (MM), it remains an incurable disease, characterized primarily by cycles of remission and relapse. Most patients experience relapse after initial therapy, and with each subsequent line of treatment, the depth and duration of response, as well as survival outcomes, diminish. Patients with relapsed or refractory multiple myeloma who have been exposed to all three major drug classes (triple-class exposure: including immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies) often exhibit poor clinical outcomes, with low response rates (20%–30%), short duration of response (2–4 months), and reduced survival.

In the pivotal KarMMa trial conducted in patients with triple-class exposed and refractory multiple myeloma, the majority (72%) of patients achieved rapid, deep, and durable responses following a single infusion of Abecma. In this study, Abecma demonstrated a favorable and predictable safety profile, including cytokine release syndrome (CRS) and neurologic toxicity (NT), which were predominantly low-grade, early-onset, and rapidly resolving.

FDAThe approval of Abecma was based on the results of the pivotal Phase II KarMMa study. The trial was conducted in 127 patients with relapsed or refractory multiple myeloma who had received at least three prior classes of therapy (including immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies) and were refractory to the last line of treatment. The efficacy-evaluable population included 100 patients who received CAR-positive T-cell therapy with Abecma at doses ranging from 300 to 460 × 10⁶ cells. Among these patients, 88% had received four or more prior lines of therapy, and 85% were triple-class refractory.

Results showed that in the efficacy-evaluable population (n=100), the overall response rate (ORR) with a single Abecma infusion was 72% (95% CI: 62–81), and 28% of patients achieved stringent complete response (sCR; 95% CI: 19–38). Responses were rapid and durable, with a median time from infusion to response of 30 days (range: 15–88 days). The median duration of response was 11 months (95% CI: 10.3–11.4) among all responders and 19 months (95% CI: 11.4–NE) among those who achieved sCR. Among the 28 patients who achieved sCR, an estimated 65% (95% CI: 42%–81%) maintained their response for at least 12 months.

In this study, the safety of Abecma in treated patients has been well established; cytokine release syndrome (CRS) and neurotoxicity (NT) were predominantly low-grade, with predictable early onset and rapid resolution.

Abecma is the first BCMA CAR-T cell therapy to receive regulatory approval globally. Its mechanism involves engineering patients’ T cells to express a chimeric antigen receptor (CAR) targeting BCMA. The manufacturing process includes isolating T cells from each patient’s blood and transducing them with a lentiviral vector encoding the BCMA-specific antigen receptor.CarrierT cells are modified to express the BCMA receptor on their surface. For treatment, patients with multiple myeloma (MM) first undergo preconditioning with two chemotherapy drugs (cyclophosphamide and fludarabine) to eliminate existing T cells in the patient’s body, followed by infusion of bb2121. Once infused back into the patient, ide-cel begins to seek out and kill cells expressing BCMA.

Abecma is part of a co-development, co-commercialization, and profit-sharing agreement between Bristol-Myers Squibb and bluebird bio. The joint comprehensive clinical development program for Abecma by both parties includes multiple clinical studies for the early treatment of MM (KarMMa-2, KarMMa-3, KarMMa-4), including the treatment of newly diagnosed MM patients.

In addition to Abecma, Bristol-Myers Squibb (BMS) and bluebird bio are also developing bb2127, a second-generation anti-BCMA CAR-T therapy. Built upon the first-generation CAR-T therapy Abecma, bb2127 incorporates a PI3K inhibitory signal to produce a CAR-T product enriched with “memory T cells,” a longer-lived and more potent T-cell subset with improved anti-TumorActivity.

Multiple myeloma (MM) is the second most common hematologic malignancy, after non-Hodgkin lymphoma.Tumor. In recent years, despite significant advances in chemotherapy, proteasome inhibitors, immunomodulatory thalidomide derivatives, and CD38-targeted antibodies, nearly all patients eventually experience relapse. Therefore, there is an urgent need for new therapeutic regimens. The multiple myeloma (MM) market is projected to reach $29 billion by 2027.

B-cell maturation antigen (BCMA) is an extremely important B cellBiomarker, is widely expressed on the surface of MM cells and has become a focus in recent years for MM and other hematologic malignanciesTumora highly popular target for immunotherapy. Currently, there are more than 20 immunotherapies developed against BCMA, primarily categorized into three types: chimeric antigen receptor T-cell therapy (CAR-T, BMS/bluebird bio,Novartisas representative), bispecific antibodies (BsAb, with Amgen as representative), antibody-drug conjugates (ADC,GlaxoSmithKlineas a representative).

August 2020,GlaxoSmithKline(GSK) The BCMA-targeted antibody-drug conjugate (ADC) Blenrep (belantamab mafodotin, GSK2857916) has received approval in the United States and the European Union for the treatment of patients with relapsed or refractory multiple myeloma (R/R MM) who have previously received multiple therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody.

Notably, Blenrep is the first BCMA-targeted therapy approved globally. Data from the pivotal Phase II DREAMM-2 study showed that in patients with relapsed/refractory multiple myeloma (R/R MM) who had been heavily pretreated (median number of prior therapies: 7), the overall response rate (ORR) was 31% (n=30/97) in the 2.5 mg/kg dose group and 34% (n=34/99) in the 3.4 mg/kg dose group, representing clinically meaningful outcomes. Data from the DREAMM-1 study demonstrated an ORR of 60% with Blenrep treatment in BCMA-positive R/R MM patients. (Bioon.com)

Original Source: U.S. Food and Drug Administrationapproves Bristol Myers Squibb’s and bluebird bio’s Abecma (idecabtagene vicleucel), the First Anti-BCMA CAR T Cell Therapy for Relapsed or Refractory Multiple Myeloma