The FDA is set to review biologics license applications (BLA) for two multiple myeloma treatments: belantamab mafodotin combinations and linvoseltamab. These regulatory decisions could significantly impact the treatment landscape for patients with relapsed or refractory multiple myeloma, offering new hope for those who have exhausted other options. The outcomes are based on data from Phase III clinical trials DREAMM-7 and DREAMM-8 for belantamab mafodotin, and LINKER-MM1 for linvoseltamab.
Belantamab Mafodotin Combinations Under FDA Review
GSK's belantamab mafodotin (Blenrep) is under review by the FDA in combination with bortezomib plus dexamethasone (BVd) and pomalidomide plus dexamethasone (BPd) for treating multiple myeloma patients who have received at least one prior line of therapy. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of July 23, 2025.
The BLA is supported by results from the Phase III DREAMM-7 and DREAMM-8 trials. The DREAMM-7 trial compared BVd to daratumumab plus bortezomib and dexamethasone (DVd), while DREAMM-8 compared BPd to bortezomib plus pomalidomide and dexamethasone (PVd).
Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, stated, "Relapsed/refractory multiple myeloma treatment could be transformed by additional, efficacious treatment options with manageable side effects and community-based administration. The evidence from DREAMM-7 and DREAMM-8 supporting our Blenrep combinations submission has been further strengthened by the statistically significant overall survival results from the DREAMM-7 trial. We look forward to working with the FDA on this review."
DREAMM-7 and DREAMM-8 Trial Data
The DREAMM-7 trial demonstrated a statistically significant improvement in progression-free survival (PFS) for BVd compared to DVd (HR, 0.41; 95% CI, 0.31-0.53; P < .001). At a median follow-up of 28.2 months, the median PFS was 36.6 months for BVd and 13.4 months for DVd. Overall survival (OS) data, although not statistically significant at the data cutoff, favored the BVd arm, with an 18-month OS rate of 84% compared to 73% for DVd.
The DREAMM-8 trial also showed a significant improvement in PFS for BPd compared to PVd (HR, 0.52; 95% CI, 0.37-0.73; P < .001). At a median follow-up of 21.8 months, the median PFS was not reached for BPd and was 12.7 months for PVd.
Regeneron's Linvoseltamab BLA Resubmission Accepted
Regeneron Pharmaceuticals announced that the FDA has accepted for review the resubmission of the Biologics License Application (BLA) for linvoseltamab for the treatment of adult patients with relapsed/refractory (R/R) multiple myeloma (MM). The target action date for the FDA decision is July 10, 2025.
Acceptance of the BLA resubmission follows the resolution of third-party fill/finish manufacturing issues, which was the sole approvability issue identified by the FDA in the previous submission. The BLA is supported by data from the pivotal LINKER-MM1 trial investigating linvoseltamab in R/R MM, and linvoseltamab is also under review by the European Medicines Agency (EMA) for the same patient population.
Linvoseltamab Clinical Development Program
Linvoseltamab is an investigational BCMAxCD3 bispecific antibody designed to bridge B-cell maturation antigen (BCMA) on MM cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing.
The ongoing, open-label, multicenter Phase 1/2 dose-escalation and dose-expansion LINKER-MM1 trial is investigating linvoseltamab in 282 enrolled patients with relapsed/refractory MM. The Phase 1 dose-escalation portion of the trial – which is now complete – primarily assessed safety, tolerability and dose-limiting toxicities across nine dose levels of linvoseltamab and explored different administration regimens. The ongoing Phase 2 dose expansion portion is assessing the safety and anti-tumor activity of linvoseltamab, with the primary endpoint of objective response rate.
Impact on Multiple Myeloma Treatment
Multiple myeloma is the second most common blood cancer, with over 187,000 new cases diagnosed globally each year. In the U.S., an estimated 36,000 new cases will be diagnosed in 2025, with 12,000 deaths anticipated. These potential approvals represent a significant step forward in providing effective treatments for patients with relapsed or refractory multiple myeloma.
