BCMA Target Development: CAR-T, Dual Resistance, Antibody Association Drugs Who Will Win First?

The 62nd Annual Meeting of the American Society of Hematology (ASH) in 2020 will be held online, December 5-8.
this is the most important hematological event of the year and the world's largest hematology conference, and the ASH conference reported data on 29 different projects for BCMA targets, which are once again in the spotlight.
Leukocyte Mature Antigen (BCMA) is an extremely important B-cell biomarker, widely found on the surface of multiple myeloma cells, and is a very popular immunotherapy target for multiple myeloma (MM) and other hematologic malignancies.
The immunotherapy currently developed for BCMA targets is divided into three main categories: chime antigen-subject T-cell therapy (CAR-T, new-based/bluebird biology, Johnson and Johnson-Legend), dual-specific antibodies (BsAb, represented by Amgen), and antibody drug couples (represented by ADC, GSK).
as the meeting progressed, there seemed to be a consensus that cell therapy was usually more effective than bisexual antibody drugs, which were more effective than antibody drug combinations.
ADC drug is in trouble with adverse reactions, GSK, AZ affected in August this year, GlaxoSmithKline (GSK) antibody association drug (ADC) Blenrep (belantamab mafodotin-blmf) ) approved by the U.S. FDA as a monotherapy for adult patients with relapsed/refractic multiple myeloma who have previously received at least 4 therapies, including anti-CD38 monoclonal antibodies, protease inhibitors, and immunomodulation agents.
although Brainrep is the first approved anti-BCMA treatment, its adverse visual impairment reactions raise concerns and do not have much advantage over the effectiveness of other therapies currently under development.
, however, AstraZeneta's ADC drug MEDI2228 may not go that far.
in the ASH report, the drug showed higher rates of visual impairment.
in the trial, all patients eventually stopped treatment, two-thirds of them due to adverse events.
chances of meDI2228 entering clinical late-stage development are slim.
are at risk of CRS, and promoting challenged dual-specific antibody drugs works in a similar way to CAR-T therapy, both of which attempt to target T-cells to tumors.
, however, the production and management of dual-specific antibodies is easier than traditional CAR-T.
traditional CAR-T must be customized for each patient, and dual-specific antibody drugs are more likely to be mass-produced.
, the latest data may pour cold water on the idea.
in several trials, about 40 to 50 percent experienced cytokine release syndrome (CRS), which means that to ensure the safety of treatment, patients may have to be treated in large hospitals to be able to process CRS in a timely manner.
, dual-specific antibodies may face similar promotional challenges to CAR-T therapies.
this could be particularly troubling for AMG 701, with trial data showing that 9 percent of patients treated with antibodies had grade 3 or more CRS, which is higher than CRS rates in other dual-specific drugs or even some CAR-T therapies.
competition for cell therapy, ready-made therapy or the next breakthrough worldwide, the fastest-growing BCMA cell therapy is new base and bluebird bb-2121.
the product is a second-generation chisellular antigen-insular (CAR) T-cell therapy, which has been submitted to the FDA for the treatment of multiple myeloma.
is expected to be the second BCMA treatment.
, a new generation of ready-made cell therapies, represented by Allogene, has shown good potential.
While the response rate reported on this ASH was only 60%, BMS and Bluebird showed an 82% response rate, and Johnson and Johnson and Legend showed a 97% response rate and long-term durability, Allogene and Burnett's data are still early clinical and may become more competitive as the dose increases.
addition, other start-ups using the more traditional BCMA CAR-T method made their debuts, with Poseida showing four reactions in six patients using the new manufacturing method and Arcellx showing six reactions in six patients, including four full reactions.
It's worth noting that even if patients develop resistance to BCMA-targeted drugs, they won't stop expressing BCMA, which means researchers can try giving bis specific antibody drugs first, then CAR-T treatment, and vice versa, to prolong the recurrence of cancer."
the rapid rise of the domestic BCMA therapy Nanjing legendary biological CAR-T therapy LCAR-B38M/JNJ-4528, is currently a hot domestic research products.
In June 2017, Legendary Creatures became the brightest dark horse in the industry at the time, with data (100% objective remission rate) for the treatment of recurring recurring resuscable multiple myeloma with LCAR-B38M/JNJ-4528 CAR-T cell therapy.
, the product was added to the list of breakthrough drugs by CDE, and the Drug Administration released the Breakthrough Therapeutic Drug Review Procedure (Trial) document on July 8.
Cozi Bio-developed all-human anti-BCMA CAR-T cell (CT053) has obtained clinical trial licenses from the China Drug Administration (NMPA), the U.S. Food and Drug Administration (FDA) and Health Canada, has been qualified as FDA Advanced Therapy for Regenerative Medicine (RMAT) and "Orphan Medicine" and has been approved by the European Medicines Regulatory Agency (EMA) in the Priority Medicines (PRIME) program and granted "Orphan Drugs".
Summary has done well for pharmaceutical companies, with several projects targeting BCMA, meaning that the field is becoming increasingly competitive and that some companies may lose out to other, stronger companies, even if they achieve positive results.
treatments that can really cure patients are not yet available, and businesses still need to continue their efforts.
source: #ASH20 saw a BCMA brawl. Who's still standing? And who got knocked out for good?