Linvoseltamab-gcpt (Linzyopic) Receives FDA Accelerated Approval for Quadruple-Refractory Multiple Myeloma
FDA Accelerated Approval and Indication
The U.S. FDA approved linvoseltamab-gcpt (Linzyopic) from Regeneron Pharmaceuticals (REGN) on July 2, 2025, under accelerated approval. This bispecific antibody simultaneously targets B-cell maturation antigen (BCMA) and CD3 on T cells, inducing cancer cell death. It is indicated for adult patients with relapsed or refractory multiple myeloma who have received a minimum of four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. While administered intravenously, patients with sufficient response can have their dosing interval extended from every two weeks to every four weeks, which reduces the burden of long-term treatment.
Clinical Evidence and Safety
The approval is based on efficacy data from the open-label, multi-center Phase 1/2 LINKER-MM1 trial (NCT03761108), with an analysis of 80 patients. The objective response rate (ORR), as assessed by the independent review committee, was 70%, with a 95% confidence interval of 59-80%, and the proportion of patients achieving complete response or better was 45%. The median duration of response was 11.3 months, with response rates of 89% at 9 months and 72% at 12 months. However, in the recommended dose group, 46% of patients experienced cytokine release syndrome (CRS), 54% experienced neurotoxicity, and 38% experienced Grade 3 or 4 infections, making boxed warnings and a risk evaluation and mitigation strategy (REMS) critical for commercialization.
Regulatory History
Regeneron submitted BLA 761400 in December 2023, but the FDA issued a complete response letter (CRL) in August 2024 due to issues with a pre-approval inspection of a third-party fill and finish facility. The only obstacle to approval was not related to clinical efficacy or the safety of the product itself, but rather to manufacturing facility issues. After resolving these issues, the application received priority review and was ultimately approved in July 2025. The FDA's public review records did not include an advisory committee (AdComm) meeting or a vote. In the European Union, the EMA CHMP issued a positive opinion on February 27, 2025, followed by conditional marketing authorization on April 23, 2025. As of April 2026, the Japanese clinical registration data is classified as an unapproved drug in the PMDA system.
Market and Competitive Landscape
The global market for multiple myeloma treatments was estimated at approximately USD 29.24 billion in 2025, but the initial commercial market for linvoseltamab-gcpt is focused on patients who have failed multiple prior therapies. Direct competitors include teclistamab-cqyv (Tecvayli) from Janssen and elranatamab-bcmm (Elrexfio) from Pfizer, both of which received FDA accelerated approval on October 25, 2022, and August 14, 2023, respectively. Talquetamab-tgvs (Talvey), which targets GPRC5D and CD3, and BCMA CAR-T therapies such as ciltacabtagene autoleucel (Carvykti) and idecabtagene vicleucel (Abecma) are also competing for patients. Linvoseltamab-gcpt's high response rate and the potential for monthly administration based on response are competitive advantages, but demonstrating clinical benefit in a confirmatory trial is necessary to maintain accelerated approval and expand its use to earlier lines of therapy.
With an ORR of 70% and a complete response rate of 45% in the Phase 1/2 trial, the approval of linvoseltamab-gcpt provides Regeneron (REGN) with a commercial foothold in the approximately USD 29.24 billion multiple myeloma market. In the short term, the dosing schedule of every four weeks based on response will be a key differentiator in the market for patients with quadruple-refractory BCMA- and CD3-targeting therapies, which is currently dominated by Tecvayli and Elrexfio. However, the REMS and the requirement for initial hospitalization may limit adoption and the number of treatment centers. From a research and development perspective, the accelerated approval is based on data from a single-arm study of 80 patients, so the results of the confirmatory trial, including survival and duration of response, as well as the management of infections, CRS, and neurotoxicity, will be critical for maintaining approval. In the medium to long term, the value will depend on expansion to earlier lines of therapy, commercial success in the U.S. and EU, and regulatory progress in Japan, in competition with CAR-T therapies such as Carvykti and Abecma, and GPRC5D-targeting therapies such as Talvey.
Source: openFDA (api_fda)
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=BLA761400