FDA Reviews Linvoseltamab in Relapsed/Refractory Multiple Myeloma
The FDA has accepted the resubmitted biologics license application for linvoseltamab to treat relapsed/refractory multiple myeloma in heavily pretreated adults.
- The FDA has accepted the resubmitted biologics license application (BLA) for linvoseltamab (REGN5458) for the treatment of heavily pretreated adults with relapsed/refractory multiple myeloma.
- The agency's Prescription Drug User Fee Act (PDUFA) target action date is July 10, 2025.
- Data from the phase 1/2 LINKER-MM1 trial (NCT03761108) support this regulatory decision.
The FDA has accepted the resubmitted BLA for linvoseltamab, a treatment for adult patients with relapsed/refractory multiple myeloma who have undergone at least 4 prior lines of therapy or 3 prior lines with refractoriness to the last regimen.1
The FDA has set a PDUFA target action date of July 10, 2025, for its decision.
In August 2024, the FDA issued a complete response letter regarding the BLA for linvoseltamabfor the treatment of patients with relapsed/refractory multiple myeloma that has advanced after at least 3 prior therapies.2 According to Regeneron Pharmaceuticals, Inc., the drug developer, the only approvability concern came from data found during a preapproval inspection of a third-party fill/finish manufacturer for a different company's product candidate. The manufacturer then indicated that they believe the issue to be resolved.
Linvoseltamab is also currently under review by the European Medicines Agency for the same patient population and has not been approved by any regulatory authority.
“The emergence and approval of bispecific antibodies in multiple myeloma expands our armamentarium to treat patients,” Surbhi Sidana, MD, said during an Oncology Town Hall™ virtual meeting sponsored by Physicians Education Resource®(PER®). during the meeting. “I think it’s wonderful that we have so many choices with even more approaches on the horizon, including linvoseltamab. We anticipate additional FDA approvals in the near future.”
Microscopic photorealistic image of myeloma cells - Generated with Google Gemini AI
LINKER-MM1
Results from LINKER-MM1, an open-label, multicenter, dose-escalation, and dose-expansion trial, served as the basis for this BLA submission. The study included patients aged 18 years or older with relapsed/refractory multiple myeloma who had an ECOG performance status of 0 or 1 and measurable serum or urine markers per the International Myeloma Working Group (IMWG) criteria.3
The primary end point for phase 2 was overall response rate (ORR) by independent review committee (IRC) assessment and IMWG criteria, and secondary end points included duration of response, progression-free survival, ORR by investigator assessment, overall survival, and safety.
According to data from the phase 1/2 LINKER-MM1 trial, linvoseltamab given at a 200-mg dose (n = 117) led to an ORR of 71% as assessed by an IRC, with a complete response (CR) or better rate of 46%.3
Updated data were then presented at the 2024 European Hematology Association Congress, showring that at a median follow-up of 14.3 months, the ORR was maintained at 71%. At this time, the CR or better rate was 50%.4 Further analysis revealed a stringent CR rate of 44.4%, a CR rate of 5.1%, a very good partial response (VGPR) rate of 13.7%, and a PR rate of 7.7%.
Looking at safety, all patients treated with the 200-mg dose had adverse events (AEs), and 85% of patients experienced grade 3 or higher AEs. The most common AE was cytokine release syndrome (CRS; 46%). Of those with CRS, 35% were grade 1, 10% were grade 2, and 1% were grade 3. Further, any grade adjudicated immune effector cell-associated neurotoxicity syndrome (ICANS) was seen in 8% of patients, grade 3 ICANS was seen in 3 patients, and no patients experienced grade 4 or higher ICANS. Infections of any grade were seen in 73% of patients, and 34% were grade 3/4.
For grade 3/4 AEs, the most commonly seen were neutropenia (30.8%), anemia (23.9%), thrombocytopenia (13.7%), and lymphopenia (11.1%). The most common nonhematologic treatment-emergent AEs (TEAEs) in this cohort were CRS (45.3%), cough (33.3%), fatigue (32.5%), and diarrhea (32.5%). Twelve percent of patients died due to their TEAEs during treatment or within 30 days after the last dose, 9% of which were due to infections.
Further Development
Linvoseltamab is being evaluated in an extensive clinical development program assessing its potential both as a monotherapy and in combination regimens across various treatment settings for multiple myeloma, including earlier lines of therapy and plasma cell precursor disorders.1
Ongoing studies include the phase 1b LINKER-MM2 trial (NCT05137054), which explores linvoseltamab in combination with other therapies for relapsed/refractory multiple myeloma, and the phase 3 LINKER-MM3 trial (NCT05730036), a confirmatory study investigating its efficacy as a monotherapy in this patient population.
REFERENCES:
Linvoseltamab BLA accepted for FDA review for the treatment of relapsed/refractory multiple myeloma. News release. Regeneron Pharmaceuticals, Inc. February 11, 2025. Accessed February 11, 2025. https://tinyurl.com/23ft5enz
Regeneron provides update on biologics license application for linvoseltamab. News release. Regeneron Pharmaceuticals, Inc. August 20, 2024. Accessed February 11, 2025. https://tinyurl.com/y64ed93c
Jagannath S, Richter J, Dhodapkar MV, et al. Linvoseltamab, a B-cell maturation antigen-targeted T-cell-engaging bispecific antibody in patients with relapsed or refractory multiple myeloma, including difficult-to-treat subgroups. Presented at: 2024 AACR Annual Meeting; April 5-10, 2024; San Diego, CA. Abstract CT001.
Lentzsch S, Bumma N, Lee HC, et al. Linvoseltamab in patients with relapsed/refractory multiple myeloma in the LINKER-MM1 study: depth and durability of response at 14-month median follow-up. Presented at: 2024 EHA Congress; June 13-16, 2024; Madrid, Spain. Abstract S212.
