Regeneron Pharmaceuticals Presents Promising Initial Results from LINKER-MM2 Trial of Linvoseltamab Combinations for Relapsed/Refractory Multiple Myeloma at ASCO 2025

Regeneron announced positive Phase 1b trial results for linvoseltamab in relapsed/refractory multiple myeloma, demonstrating high objective response rates of 90% when combined with carfilzomib and 85% with bortezomib; these findings, presented at ASCO 2025, highlight the drug's potential in heavily pre-treated patients, although safety data revealed significant adverse events like neutropenia and infections. A registrational Phase 3 trial is planned to investigate the linvoseltamab and carfilzomib combination, while the FDA's decision on linvoseltamab in the U.S. is expected by July 10, 2025.

Analysis

Regeneron's linvoseltamab has demonstrated notable efficacy in combination therapies for relapsed/refractory (R/R) multiple myeloma, as indicated by initial Phase 1b LINKER-MM2 trial data. Specifically, linvoseltamab combined with carfilzomib achieved a 90% objective response rate (ORR) with a 76% complete response (CR) rate, while the bortezomib combination yielded an 85% ORR with a 50% CR rate in heavily pre-treated patients. These high response rates, presented at ASCO 2025, underscore the drug's potential clinical activity. However, these promising efficacy results are counterbalanced by significant safety concerns, with serious adverse events (SAEs) occurring in 83% of patients in both cohorts, including high rates of neutropenia (65% with carfilzomib, 54% with bortezomib), cytokine release syndrome (61% and 58% respectively), and infections (91% and 75% respectively), with one treatment-related fatality in each arm. Linvoseltamab monotherapy (Lynozyfic™) is approved in the EU, and a U.S. FDA decision is anticipated by July 10, 2025, though these combination regimens remain investigational. A registrational Phase 3 trial for the linvoseltamab-carfilzomib combination is planned, signalling a path towards broader approval. Institutional investor activity in Q1 2025 was mixed, with 649 additions versus 771 decreases in REGN shares, including significant divestments by JPMORGAN CHASE (-19.8%) and CAPITAL WORLD INVESTORS (-30.2%), juxtaposed with substantial new or increased positions by firms like TWO SIGMA ADVISERS and GOLDMAN SACHS. Recent analyst ratings are positive, with two 'Buy' or 'Overweight' ratings issued and a median price target of $850.0.

Key Decisions for Investors

• Investors should weigh the high efficacy data of linvoseltamab combinations against the significant reported adverse event profile, particularly the 83% SAE rate and treatment-related fatalities, which could impact regulatory perspectives and market adoption.
• Closely monitor the upcoming FDA target action date of July 10, 2025, for linvoseltamab monotherapy, as this will be a key catalyst, and track progress of the planned Phase 3 trial for the carfilzomib combination for insights into long-term viability.
• Consider the mixed institutional sentiment, with notable Q1 2025 divestitures by major funds alongside strong buy-ins from others, suggesting a period of re-evaluation that warrants careful due diligence on risk-reward.
• Evaluate the potential market opportunity in R/R multiple myeloma, given the high unmet need, but factor in the competitive landscape and the time and risk associated with bringing investigational combination therapies to market.