GSK's Withdrawn ADC Blenrep Shows Promise of Revival with Positive Phase III DREAMM-7 Results

Will BCMA ADC Be Reborn from the Ashes?

DREAMM-7 StudyA total of 494 patients with R/R MM were enrolled and randomly assigned in a 1:1 ratio to receive either Blenrep+BorDex or daratumumab+BorDex combination therapy. These patients had previously received at least one prior treatment and experienced disease progression during or after their most recent therapy.

The primary endpoint of the trial was PFS assessed by an independent review committee, with key secondary endpoints including OS, duration of response, etc.

The results showed that, compared with daratumumab+BorDex (bortezomib+dexamethasone), the combination therapy of Blenrep+BorDex significantly extended the time to disease progression or death in patients. In addition, a significant and clinically meaningful OS trend was observed. The trial is still ongoing to further monitor OS outcomes.

Blenrep (Belantamab mafodotin) is a BCMA-targeted ADC therapy that received accelerated FDA approval in August 2020 for the treatment of patients with multiple myeloma (MM) who have failed four prior lines of therapy. In November last year, GSK announced the initiation of the withdrawal process for Blenrep's U.S. marketing authorization at the request of the FDA, following the failure of the confirmatory Phase III DREAMM-3 clinical trial.

Unlike DREAMM-7, the DREAMM-3 study evaluated the efficacy of Blenrep monotherapy compared to pomalidomide and low-dose dexamethasone. The patients enrolled in this study were ≥2-line R/R MM patients previously exposed to lenalidomide and proteasome inhibitors (PI).

Questions about the efficacy of Blenrep as a single agent do not completely negate Blenrep; its combination with current standard treatment options may offer more choices for R/R MM patients and could potentially lead to its reapproval. Currently, apart from DREAMM-7, Blenrep is also being studied in the DREAMM-8 trial, which investigates its use in combination with pomalidomide and dexamethasone (B-Pd) versus bortezomib, pomalidomide, and dexamethasone (PVd) for the treatment of R/R MM. The primary endpoint is expected to be reached by September next year.

For enterprises, whether they can successfully develop a new drug depends significantly on identifying the product's own advantages, positioning, and how to precisely screen the benefiting population.

According to the Insight database,CurrentlyOnly 5 products globallyBCMA ADC Entering the clinical stage, mainly dominated by overseas pharmaceutical companies.

However, AstraZeneca's MEDI2228 was previously terminated in Phase II clinical development for multiple myeloma due to adverse reactions. Meanwhile, Amgen has also adjusted its strategic layout, halting all BCMA candidate drugs in its R&D pipeline, including the BCMA ADC AMG224.

Notably, HDP-101, which Huadong Medicine has acquired at a high price from Heidelberg Pharma, is a product based onDeveloped by the ATAC platformTargeted BCMA ATAC drugs.

According to the introduction, the ATAC technology platform utilizes a novel toxin, Amanitin (alpha-Amanitin) and its derivatives, as the cytotoxic payload in a new type of ADC drug. This drug exhibits tolerance, stability, safety, and enhanced efficacy. Unlike other chemotherapy drugs and ADCs that target rapidly dividing tumor cells, Amanitin not only kills fast-dividing tumor cells but is also effective against tumor cells in a dormant phase.

However, in China, these 5 ADCs onlyBlenrep Entering the clinical stage, simultaneously launching in ChinaDREAMM-3、DREAMM 7、DREAMM 8 3 Phase III.

In China, the development of novel drugs targeting BCMA mainly focuses on CAR-T,Dual AntibodyProducts.

Distribution of Categories of Targeted BCMA Drugs Under Research in China

Source: Insight Database Web Version (Same as below)

In terms of CAR-T,The largest number of layouts, with 107 products globally already entering clinical trials,In China, there are 62 products. Moreover, at the end of June this year, the CAR-T therapy Idecabtagene Vicleucel developed by IASO Biotherapeutics and Innovent Biologics was approved for marketing.Becoming the firstBCMA-targeted CAR-T therapy approved for marketing in China. Also became the successor toBMS/Bluebird (Bluebird Bio)Idecabtagene vicleucel, Legend Biotech/Johnson & Johnson's Cilta-cel, the third approved CAR-T therapy globally,BCMA CAR-T。

In China, there are two other products in the application stage for market launch:Johnson & Johnson/Legend BiotechCilta-cel December 2022 ReportCARsgen Therapeutics/Huadong Medicine's Zevorcel Orsale 2022 October reported production.In addition, Simcere Pharmaceutical, UCar-T, and Hengrui Dason have also made arrangements.

In October 2022, Tecvayli, developed by Janssen, a subsidiary of Johnson & Johnson, was approved by the FDA for marketing, becoming the world's first approved BCMA-targeted bispecific antibody. In August this year, Pfizer's ELREXFIO (Elranatamab) received accelerated approval from the FDA.BCMA/CD3 Bispecific Antibody Cohort. Also, currently the only two approvedTargeted BCMA Bispecific Antibody.

The former has been submitted for marketing approval in China this August. In China, there are nine bispecific antibodies targeting BCMA that have entered clinical trials, all targeting BCMA/CD3. The companies involved include Connaught Biologics, CSPC Zhongqi, EpimAb Biotherapeutics, and others.

9 BCMA-Targeted Bispecific Antibodies Entering Clinical Stage in China

However, from the perspective of indication layout, whether it is BCMA ADC drugs,BCMA CAR-T orBCMA/CD3 bispecific antibody, with indications concentrated in multiple myeloma, showing a high degree of homogeneity.This is mainly due to the consistent upregulation and uniqueness of BCMA on the surface of MM cells in cell line and patient sample studies, making it widely used in the development of MM drugs.

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