Pfizer's TCE Antibody Elranatamab Granted Conditional Approval in China for Relapsed/Refractory Multiple Myeloma

On March 10, Pfizer announced its bispecific antibody new drugEnapotamab（elranatamab) has been approved by the National Medical Products Administration（NMPA）Conditionally approved for marketing,Applicable to patients who have received at least three prior lines of therapy(Including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody)Treatment of adult patients with relapsed or refractory multiple myeloma (RRMM).

Elnatuzumab is a bispecific antibody that simultaneously targets B-cell maturation antigen (BCMA) and CD3.It can bind to BCMA on myeloma cells and CD3 on T cells, thereby activating T cells to kill myeloma cells.August 2023, EnatuzumabReceived accelerated approval from the U.S. FDA for the treatment of relapsed/refractory MM patients.

The press release introduced that the approval of Enfortumab in China this time is based on the clinically significant overall response rate and duration of response from the global pivotal Phase 2 single-arm study MagnetisMM-3 and the separate Chinese Phase 1b/2 single-arm study MagnetisMM-8. The clinical research data of MagnetisMM-3 showed,With a median follow-up of 33.9 months, enfortumab monotherapy for triple-refractory RRMM patients continues to demonstrate deep and durable efficacy, with the median duration of response (mDOR) not yet reached, and the 30-month DOR rate at 61.0%.Median progression-free survival (PFS) was 17.2 months, and median overall survival (OS) was 24.6 months., and no new safety signals were observed.

In February this year, Johnson & Johnson's talquetamab injection received NMPA approval for marketing in China. The indication is: as a monotherapy for adult patients with relapsed or refractory multiple myeloma (RRMM) who have previously received at least three lines of therapy. Previously, in June 2024, Johnson & Johnson's teclistamab was approved for marketing in China, also for monotherapy in later-line treatment of RRMM.

It is worth noting that,Both Tarquetumab and Teritumab are novel antibody drugs known as T-cell engagers (TCE).The former is a subcutaneously injected GPRC5D×CD3 bispecific antibody, and the latter is a subcutaneously injected bispecific antibody targeting BCMA and CD3. It can be seen that these two new antibody drugs share a common target, CD3, and they can be classified as TCE antibody drugs.

One end of the TCE drug is linked to tumor-associated antigens (TAA) to target tumor cells, while the other end is connected to the CD3 epitope of T cells to activate them and exert their tumor-killing effects. In terms of the drug's mechanism, TCE antibodies can bypass TCR-MHC-I interactions, triggering T-cell activation regardless of the antigen specificity of the tumor cells. This leads to the production of cytotoxic molecules, including perforin and granzymes, to kill tumor cells.

In 2024, two TCE drugs were approved for the first time globally.DLL3/CD3 TCE developed by AmgenIn May, it received accelerated approval from the U.S. FDA for the first-line treatment of adult patients with extensive-stage small cell lung cancer.As the first bispecific TCE for the treatment of solid tumorsRegeneron's CD20/CD3-targeting TCE Odronextamab was approved for marketing by the EMA in August, marking its first approval for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma or R/R diffuse large B-cell lymphoma.

By the end of 2024, 10 TCE drugs have entered the commercialization stage, with TCE research and development in full swing. As clinical validation data for TCE targeting PSMA, DLL3, and other targets in solid tumors continue to be released,The application of TCE is gradually expanding to solid tumors. Moreover, the technology for deep depletion of B cells has provided new therapeutic approaches for various autoimmune diseases such as neuroimmunological, rheumatological, and renal conditions.The future development of TCE is worth looking forward to.