GSK's BCMA-Targeted ADC Blenrep Shows Superiority Over J&J's CD38 Monoclonal Antibody in Head-to-Head Phase 3 Trial, Poised for Resurgence in Multiple Myeloma

Blenrep Combination Therapy: Significantly Reduces Risk of Death, Poised to Replace Current Standard of Care

The DREAMM clinical development program aims to evaluate the potential of Blenrep in treating earlier-stage patients and its combination with innovative therapies and standard treatment regimens. In addition to DREAMM-7, the program also includes the ongoing Phase 3 clinical trial DREAMM-8, which assesses the efficacy of Blenrep in combination with pomalidomide and dexamethasone versus bortezomib combined with pomalidomide and dexamethasone.

DREAMM-7: Unlocking Second-Line Treatment Potential for Multiple Myeloma, Aiming to Replace Johnson & Johnson's Darzalex (daratumumab)

The DREAMM-7 study is a Phase III clinical trial designed to evaluateBlenrep with Bortezomib and DexamethasoneCombined use, withDaratumumab + DexamethasoneEfficacy in the treatment of r/r MM in the second line and beyond.

Published in OctoberClinical Trial DataDisplay,The median progression-free survival (PFS) for patients receiving Blenrep combination therapy (N=243) was 36.6 months (95% CI: 28.4-NR), nearly two years longer than the 13.4 months (95% CI: 11.1-17.5) observed in the active control group (N=251)., patients receiving Blenrep combination therapyThe risk of disease progression or death was reduced by nearly 60%.(HR: 0.41, 95% CI: 0.31-0.53, p<0.00001), achieving the primary endpoint of this trial.

At a virtual investor event focused on oncology, the GSK management team emphasized the "multi-blockbuster" potential of Blenrep and positioned it as a second-line treatment for multiple myeloma. Chief Commercial Officer Luke Miels estimated during the conference call,Blenrep's peak sales may reach£3 billion (approximately $3.8 billion), and has the potential to replace Darzalex as the standard treatment for this indication.

DREAMM-8：Breaking Through Drug Resistance Barriers: BPd Regimen May Open a New Chapter in MM Treatment

The DREAMM-8 study is also a Phase III clinical trial designed to evaluateBlenrep in combination with pomalidomide and dexamethasone (BPd regimen) versus bortezomib, pomalidomide, and dexamethasone (PVd regimen)Efficacy and safety in MM patients who relapsed after ≥1 prior line of therapy (including lenalidomide).

GSK announced the latest research progress at the 29th Annual Meeting of the European Hematology Association (EHA) in June this year: the median PFS for patients receiving Blenrep combination therapy (N=155) has not yet been reached (95% CI: 20.6-NR), while the PFS for patients in the active comparator group (N=147) was 12.7 months (95% CI: 9.1-18.5).The risk of disease progression or death was reduced by nearly 50%.(HR: 0.52, 95% CI: 0.37-0.73, p<0.001), achieving the primary endpoint of this trial. In addition, the Blenrep combination therapy showed benefits in the analysis of all predefined subgroups.

As for the key secondary endpoint OS, the median OS for both groups has not been reached yet, but the Blenrep combination therapy has already shown a trend superior to the active control drug (HR: 0.77, 95% CI: 0.53-1.14), and the follow-up for OS is still ongoing. Notably,Blenrep Combination Therapy Also Shows Superiority in Depth of Response Compared to Active Control Group; The Proportion of Patients Receiving Blenrep Combination Therapy Achieving Complete Response Is More Than Double That of the Control Group.

GSK Plans to Share DREAMM-8 Trial Data with US, Japanese, and EU Regulatory Agencies in the Second Half of 2024, Aiming for Second-Line Approval to Bring Blenrep Back to the Market.

Blenrep is an antibody-drug conjugate comprised of a humanized B-cell maturation antigen monoclonal antibody linked to the cytotoxic agent auristatin F via a non-cleavable linker. The drug-linker technology is licensed from Seagen Inc.; the monoclonal antibody is produced using POTELLIGENT technology licensed from BioWa Inc. (a subsidiary of Kyowa Kirin Group).

In August 2020, Blenrep received accelerated approval from the FDA for adult patients with relapsed/refractory multiple myeloma who have previously received at least four therapies, including anti-CD38 monoclonal antibodies, proteasome inhibitors, and immunomodulatory agents. In the same month, it was also approved by the European Medicines Agency (EMA).

Blenrep Becomes the First FDA-Approved BCMA-Targeted Drug to Reach the Market. Despite its approved indication being for late-line treatment of MM, Blenrep generated $122 million in revenue throughout 2021 and exceeded $100 million in revenue in the first half of 2022, demonstrating significant growth potential in the pharmaceutical market due to its first-mover advantage.

However,Due to the confirmatory Phase III clinical trial DREAMM-3 not meeting its clinical endpoint, GSK withdrew this indication in the United States and the European Union in 2022 and 2023, respectively.However, GSK has not abandoned the drug and has been advancing the accessibility of Belantamab mafodotin in other regions, such as China, while actively exploring new clinical trial protocols (e.g., DREAMM-7 and DREAMM-8, which are currently showing positive data), to support the drug's return to the market.

Currently, Blenrep has a great opportunity to become a second-line treatment for MM in combination regimens. However, in the MM field, there are already two CAR-T products and two bispecific antibody products targeting BCMA that have been approved by the FDA for the treatment of r/rMM.

Currently Approved MM Immunotherapy Drugs Targeting BCMA

Abecma

Abecma is a CAR-T product targeting BCMA jointly developed by BMS and Bluebird Bio, which relies on72% Objective Response RateIn 2021, it received FDA approval for the treatment of multiple myeloma patients who have previously received at least four therapies.Becoming the world's first targeted BCMA CAR-T cell therapy.

Carvykti

Cilta-cel (Carvykti was initially developed by Legend Biotech. In December 2017, Legend partnered with Janssen, a subsidiary of Johnson & Johnson, to jointly advance the clinical development and commercialization of this therapy. It received FDA approval in February 2022.Becoming the first China-produced CAR-T therapy to gain FDA approvalIn the clinical Phase II trial, Carvykti achieved an objective response rate as high as 98%, with 78% of patients reaching stringent complete remission. Notably,In April this year, Carvykti was approved by the FDA for second-line indications, becoming the first and only B-cell maturation antigen (BCMA) targeted therapy approved for second-line treatment of patients with multiple myeloma.。

After the launch of Cilta-cel, with a better remission rate, its sales continued to climb. From 2023, Carvykti has overtaken Abecma with approximately $500 million in annual sales. The latter's sales in the same period were $472 million, increasing by 21.65% year-on-year. Thereafter, the gap between the two may continue to widen.

According to Johnson & Johnson's latest financial report, Carvykti's sales for the first three quarters of 2024 totaled $629 million, representing a year-on-year increase of 84.3%. Thus,Carvykti is expected to reach the $1 billion mark in 2024, becoming a blockbuster drug.The industry predicts that Carvykti will reach an annual sales peak of $5 billion.

In addition to the highly effective BCMA CAR-T, teclistamab and Elranatamab, the BCMA/CD3 bispecific antibodies from Johnson & Johnson and Pfizer respectively, also demonstrate significant efficacy in treating r/r MM.

Teclistamab

Teclistamab, a BCMA/CD3 bispecific antibody developed by Johnson & Johnson, was approved for marketing by the EU and FDA in August and October 2022, respectively. It is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have previously received at least four prior lines of therapy, including proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies. The FDA's approval was primarily based on positive results from the Phase I/II MajesTEC-1 study: patients achieved deep and durable responses, with an ORR of 63% (104/165). Notably, 58.8% of patients achieved very good partial response or better (≥VGPR), and 39.4% achieved complete response (CR); the median progression-free survival was 11.3 months, and the median overall survival was 18.3 months.

In February 2024, the supplemental Biologics License Application (sBLA) for Talituzumab was again approved by the FDA.Approval, used to reduce the dosing frequency for RRMM patients to once every two weeks (1.5mg/kg), in those who have achieved and maintained complete response (CR) for at least six months. In June 2024, Teclistamab gained recognition based on its effects in Chinese patients.76.9% Overall Response RateApproved by the National Medical Products Administration (NMPA) for marketing in China, intended for adult patients with relapsed or refractory multiple myeloma (RRMM) who have previously received at least three prior lines of therapy.

Elranatamab  

In November 2022, Pfizer's investigational cancer immunotherapy elranatamab received Breakthrough Therapy Designation (BTD) from the U.S. FDA for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). This Breakthrough Therapy Designation was based on the 6-month follow-up data from Cohort A (n=123) in the Phase 2 MagnetisMM-3 clinical trial: the data analysis showed,During the median follow-up period of 6.8 months, the overall response rate (ORR) for patients receiving 76 mg elranatamab subcutaneous injections weekly was 61.0%. Among the responding patients, there was a 90.4% probability of maintaining the response for ≥6 months.In January this year, the CDE website showed that Pfizer's CD3/BCMA bispecific antibodyElranatamab（Elrexfio) Submit for marketing approval in China,For the treatment of relapsed or refractory multiple myeloma (R/R MM) in patients who have received prior therapy。

Summary

As a biomarker on the surface of MM cells, the widespread presence of BCMA has sparked enthusiasm among numerous pharmaceutical companies to develop targeted BCMA therapies. According to the Insight database, there are currently nearly 180 BCMA therapies in clinical research. Amidst the siege of CAR-T, bispecific antibodies, and others, whether Blenrep can achieve good results in the fiercely competitive market in the future remains to be seen. We will continue to monitor its progress.

Source: Medical Circle - Hematology Channel, Insight DataLibrary, Hematological Oncology Information, Company Official Website