BCMA target is strong, who can be proud of the arena?

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Recently, news of BCMA targets has continued

As a key diagnostic marker and treatment target for multiple myeloma (MM), BCMA has been deployed by many companies one after another

01 BCMA

The full name of BCMA is B cell maturation antigen, which is a member of the tumor necrosis factor receptor family

The main ligands of BCMA are BAFF and APRIL

Figure 1: Schematic diagram of BCMA ligand

02 BCMA ADC

Blenrep (Belantamab mafodotin, GSK2857916) is a BCMA ADC drug developed by GSK, and it is also the world's first BCMA ADC drug

Blenrep structure:

(1) Antibody: J6M0 is a fully humanized anti-BCMA monoclonal antibody, which enhances the binding ability of monoclonal antibody FcR through desalination and alcosylation in the Fc region, and can more effectively block the binding of BCMA to BAFF/APRIL The downstream pathway of activated NF-kB down-regulates the expression of anti-apoptotic proteins and up-regulates the expression of pro-apoptotic proteins

(2) Linker: Linker cannot be split and has no bystander effect

(3) Payload: Blenrep uses MMAF as its payload.

Figure 2: Schematic diagram of Blenrep structure

Blenrep's approval for marketing is based on the pivotal DREAMM-2 study.

In terms of adverse events, Blenrep grade 3 or above adverse events include corneal lesions/microcystic epithelial changes (MEC; 46%), thrombocytopenia (22%), anemia (21%), decreased lymphocyte count (13%), and Decreased neutrophils (11%)

In 2020, ASCO also announced the data of Blenrep combined with bortezomib/dexamethasone in the treatment of MM.

03 BCMA double antibody

The BCMA double antibody can simultaneously target BCMA on myeloma cells and CD3 on T cells, and kill myeloma cells with high BCMA expression by recruiting T cells.

Figure: Mechanism of action of Janssen teclistamab

From the design point of view, most of the double-antibody products are administered intravenously, while the double-antibody products of Janssen and Pfizer are administered subcutaneously.

From the analysis of effectiveness data, Janssen’s Telistamab has an overall ORR of 65%, followed by Abbvie’s TNB-383B, which has an ORR of 52%.

For double antibody products, the speed of research and development is the first element

04 BCMA CAR-T

Abecma is the first CAR-T therapy targeting B cell maturation antigen (BCMA), which is jointly developed by BMS and Bluebird and is approved for marketing.

However, Abecma’s pricing is too high, with a total price of US$419,500, which may be twice the price of bi-antibody therapy
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Johnson & Johnson/Legendary Bio's BCMA CAR-T is also in hot pursuit.
It has submitted a BLA application to the FDA in December 2020.
According to the latest data disclosed by 2021ASCO, the ORR is 95%, the CR is 75%, and the CRS is level 3 or above.
The incidence rate is 10%, and there is no neurotoxicity (NT) above grade 3.
The data has obvious advantages over Abecma
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In addition, the drug is exploring the adaptability of outpatient medication, and it is expected to reduce the overall cost of CAR-T drugs in the future
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05 Summary

The treatment method targeting BCMA is showing a flourishing prosperity.
A new generation of therapies such as double antibodies, ADC and CAR-T are all on the battlefield.
From the perspective of curative effect, CAR-T therapy is distinguishing itself by virtue of its higher ORR and CR.
Security risks, including CRS and NT risks, should not be underestimated
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The double antibody and ADC drugs are not to be outdone, and the combination plan is expected to further improve the efficacy, but the increased safety risk is also worth considering
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However, the exact geometry of the BCMA track is still worthy of in-depth discussion.
After all, whether it is CAR-T therapy, or double antibodies and ADC, all have been approved for MM indications that have received four or more therapies in the past.
Limited
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Perhaps, who can be the first to be approved for front-line indications and be the first to shake the position of lenalidomide, bortezomib, daretuzumab and other drugs, who can truly be proud of the world
.