GSK's Blenrep Demonstrates Significant Survival Benefit in Phase III DREAMM-7 Trial for Relapsed/Refractory Multiple Myeloma

On November 14, 2024, local time, GSK announced significant progress of its antibody-drug conjugate Blenrep (belantamab mafodotin) in the treatment of multiple myeloma. The phase III DREAMM-7 trial showed that, compared with Johnson & Johnson's Darzalex (daratumumab), Blenrep demonstrated notable advantages in second-line treatment for multiple myeloma, with better survival outcomes for patients.

Multiple Myeloma is the third most common blood cancer globally, often considered treatable but difficult to cure, with more than 180,000 new diagnosed cases annually worldwide. Existing treatments often have limited efficacy, making the research into new therapies crucial.

Blenrep is an antibody-drug conjugate that contains a humanized B-cell maturation antigen monoclonal antibody linked to the cytotoxic agent auristatin F via a non-cleavable linker. Its mechanism of action targets the BCMA protein expressed on multiple myeloma cells, and when the microtubule inhibitor payload carried by the drug is released into cancer cells, it triggers cell cycle arrest and death.

In August 2020, the U.S. FDA initially approved Blenrep under the accelerated pathway as a monotherapy for patients with multiple myeloma who had progressed after prior treatment with immunomodulatory agents, anti-CD38 antibodies, and proteasome inhibitors. However, to maintain Blenrep's market position, GSK conducted the Phase 3 confirmatory DREAMM-3 study. But in November 2022, when the study failed to meet its primary efficacy endpoint, GSK had to withdraw the drug.

Nowadays, the DREAMM-7 study brings new hope for Blenrep. This is a multicenter, open-label, randomized trial evaluating the efficacy and safety of Blenrep in combination with bortezomib and dexamethasone (BorDex) versus daratumumab combined with BorDex in patients with relapsed or refractory multiple myeloma. A total of 494 participants were randomly assigned to different treatment regimens at a 1:1 ratio. The primary endpoint is progression-free survival (PFS), and key secondary endpoints include overall survival (OS), duration of response, and minimal residual disease negativity rate, among others.

In June 2024, GSK announced the progression-free survival data from the DREAMM-7 trial, showing that compared to Darzalex, Blenrep reduced the risk of death or disease progression by 60%. On Thursday, follow-up data released by GSK indicated that, compared to the Darzalex-based combination, the reduction in mortality risk for patients treated with the Blenrep-based regimen was statistically and clinically significant. The full data will be presented at the 2024 American Society of Hematology Annual Meeting in December.

In addition to DREAMM-7, GSK's DREAMM clinical development program also includes the ongoing Phase 3 DREAMM-8 trial, which evaluates the efficacy of belantamab in combination with pomalidomide and dexamethasone versus bortezomib combined with pomalidomide and dexamethasone. Furthermore, a Phase 3 study for newly diagnosed transplant-ineligible multiple myeloma is expected to commence by the end of 2024.

In 2024, the combination therapy of belantamab mafodotin has been submitted for marketing approval or received Breakthrough Therapy Designation in multiple countries and regions, including the United States and the European Union. Luke Miels, Chief Commercial Officer of GSK, estimated during a teleconference that Blenrep's peak sales could exceed $3 billion and it might potentially replace Darzalex as the standard of care for this indication.