BMS/Bluebird multiple myeloma CAR-T therapy FDA cold EU accelerated review!

BMS and partner Bluebird Bio recently announced that the European Medicines Agency (EMA) has accepted the marketing authorization application (MAA) for idecabtagene vicleucel (ide-cel, bb2121)The EMA has confirmed the integrity of the MAA and has initiated a centralized review processIn March, ide-cel was granted accelerated assessment by EMA, and its MAA review cycle will be shortened to 150 dayside-cel is a research B-cell mature antigen (anti-BCMA)-oriented chimeric antigen receptor (CAR) T-cell therapy developed for treatment for patients with recurrent/incurable multiple myeloma (R/R MM) for MM adult sin who has received at least three therapies (including immunomodulators, protease inhibitors, anti-CD38 antibodies)In March, BMS and Bluebird Bio filed an application for a biological product license (BLA) with the same indication to the FDABut it's worth noting that in mid-May, the FDA issued a refusal notice (refusal-to-file letter) to accept the BLAAfter a preliminary review, the FDA concluded that the Chemistry, Manufacturing and Control (CMC) module in the BLA requires further details to complete the reviewBut the agency did not require additional clinical or non-clinical dataBMS plans to resubmit the BLA by the end of July 2020ide-cel regulatory filings are based on the results of the Key Phase II KarMMa studyIn the study, 128 patients who had previously received at least three treatments and were ineffective against the last treatment (without answering or progression within 60 days of treatment for treatment," according to the International Myeloma Working Group (IMWG), received a dose level of 150-450 x 1006 plus CAR for recurrent and refractive multiple myeloma patients who had received a dose level of 150-450 x 10E6 plus CAR, which was treated without a response or progression of the disease within 60 days of treatmentThese patients, with six previously received treatments, 84% were difficult to treat in all three common treatment strains, including immunomodulators (IMiD), protease inhibitors (PI) and anti-CD38 antibodies; The median follow-up time is 13.3 monthsthe study reached the primary endpoint of total mitigation rate (ORR) and the key secondary endpoint of total remission rate (CR)The security results are consistent with previously reported ide-cel dataThe data showed that the total remission rate (ORR) for all dose levels was 73%, with 33% of patients receiving full remission (CR) or severe remission (sCR)Median remission duration (DoR) was 10.7 months and patients with CR or sCR had a median DOR of 19.0 monthsMedian progression-free survival (PFS) was 8.8 months and median PFS in patients with CR or sCR was 20.2 months All patients who achieved CR or sCR and had an assessable minimal residual disease (MRD) were MRD-negative the benefits of consistent clinical significance observed across subgroups, almost all subgroups with ORR rs or more were 50% or more, including elderly and high-risk patients Total lifetime (OS) data continued to mature, with an estimated median OS of 19.4 months for all dose levels and a 12-month survival rate of 78% Results supported the favorable risk prediction of ide-cel at the target dose level of 150-450 x 10E6 CAR-T cells Detailed data will be presented at the American Society of Clinical Oncology (ASCO) 2020 Virtual Science Project on May 29 "Europe has one of the highest rates of multiple myeloma, and patients with recurrent conditions that are ineffective for standard treatment options need new treatments to improve their prognosis," said Dr Stanley Franke, Senior Vice President, Cell Therapy Development, We will continue to work with the EMA to bring ide-cel to EU patients who are battling this invasive blood cancer "
ide-cel was the first car-T cell therapy to be submitted for regulatory approval for BCMA targets and for the treatment of MM BCMA is a protein widely expressed in multiple myeloma (MM) cancer cells, making it an important potential target for the treatment of this invasive blood cancer the principle of ide-cel is to embed BCMA receptors on the patient's T cells, and the preparation process is: to obtain T cells from the separation of each patient's blood, to modify the T cells using a slow-virus vector that encodes BCMA antigen receptors, so that the surface of the T cell expresses bcMA receptors During treatment, MM patients are pre-treated with two chemotherapy drugs (cyclophosphamide and fluoradarin) to kill the existing T-cells in the patient's body, and then infusion bb2121, and once infusion is returned to the patient, ide-cel begins to find and kill cells that express BCMA previously, ide-cel was granted breakthrough drug eligibility (BTD) for the treatment of R/R MM by the FDA in November 2017 and the EU EMA as a priority drug for the treatment of R/R MM (PRIME) ide-cel is part of a joint development, promotion and profit-sharing agreement between Time Squibb and Bluebird Bio The ide-cel comprehensive clinical development program includes several clinical studies (KarMMa-2, KarMMa-3, KarMMa-4) for early treatment OF MM, including new MS in addition to ide-cel, BMS and Bluebird Bio are also developing the second generation anti-BCMA CAR-T therapy bb2127, a product further developed on the basis of the first generation CAR-T therapy ide-cel, combining a PI3K inhibitory signal to produce a CAR-T product rich in "memory T cells", a longer-lived, more potent T-cell with improved tumor resistance BCMA as the target of the research MM immunotherapy (source literature - PMID: 31277554) Multiple myeloma (MM) is the second most common hematologic malignancy after non-Hodgkin's lymphoma In recent years, almost all patients have eventually relapsed, despite significant progress in chemotherapy, protease inhibitors, immunomodulator thalidomide derivatives, and CD38 targeted antibodies Therefore, there is an urgent need for new treatment options The MM market is expected to reach $29 billion by 2027 BCMA is an extremely important B-cell biomarker, widely found on the surface of MM cells, in recent years has become a very popular immunotherapy target for MM and other blood system malignancies Currently, more than 20 immunotherapies are developed for BCMA, mainly divided into three categories: chimeric antigen receptor T-cell therapy (CAR-T, BMS/Bluebird Bio, Novo representative), bispecific antibodies (BsAb, Amgen as representative), antibody drug conjugate (ADC, GlaxoSmithKline as representative) In January and February of this year, GlaxoSmithKline (GSK) B-Cell Mature Antigen (BCMA) Targeted Antibody Drug Conjugate (ADC) belantamab mafodotin (GSK2857916, 2.5 mg/kg dose) ), respectively, received fda priority review in the United States, the EU EMA accelerated assessment, for the treatment of patients who have received a variety of treatments (including an immunomodulator, a protease inhibitor, an anti-CD38 antibody) relapse or refractory multiple myeloma (R/RMM) belantamab mafodotin has the potential to become the first BCMA targeted therapy to be available on the market In 2017, belantamab mafodotin was awarded the Breakthrough Drug Qualification (BTD) by the U.S FDA and the European Union's EMA Priority Drug Qualification (PRIME), becoming the first BCMA targeted formulation to be awarded to BTD and PRIME data from the key phase II DREAMM-2 study showed that the total remission rate (ORR) of the belantamab mafodotin 2.5 mg/kg dose group was 31% (n?30/97) and the 3.4mg/kg dose group had clinical significance in R/R MM patients with prior over-treatment (number of treatments: 7) Data from the DREAMM-1 study showed that in patients with BCMA-positive R/R MM, belantamab mafodotin treated ORR at 60% original source: European Medicines Agency Validates Bristol Myers Squibb's applications for Idecabagene Vicleucel (Ide-cel, bb2121) from Bio Valley, for more information, please download BioValley APP (http://