Regeneron Pharmaceuticals has secured accelerated US Food and Drug Administration (FDA) approval for Lynozyfic (linvoseltamab-gcpt), a bispecific antibody targeting relapsed or refractory (R/R) multiple myeloma (MM).
The approval positions Regeneron among key players in the highly competitive bispecific antibody space for MM, where Johnson & Johnson’s Tecvayli (teclistamab) and Pfizer’s Elrexfio (elranatamab) have already made strides. Tecvayli and Elrexfio generated $549 million and $57 million in revenue last year, respectively.
While Tecvayli and Elrexfio require weekly or biweekly dosing indefinitely, Lynozyfic’s response-adapted regimen allows dosing intervals to extend to four weeks, potentially improving patient convenience and reducing treatment burden.
Clinical Trial Design and Results
The FDA’s decision is based on pivotal Phase I/II data from the ongoing LINKER-MM1 trial. This open-label, multicenter study enrolled more than 300 patients with heavily pretreated R/R MM.
In the Phase I intravenous dose-escalation portion, safety, tolerability, and dose-limiting toxicities were assessed across nine dose levels, while a subcutaneous Phase I arm remains underway. Phase II dose expansion focused on safety and anti-tumor activity, with an objective response rate (ORR) as the primary endpoint and secondary endpoints including duration of response (DoR), progression-free survival, and overall survival.
Of the 80 participants, 70% had an ORR, with 45% achieving a complete response (CR) or better. The median response time to first response was 0.95 months. Median DoR was not reached, with 89% of responders maintaining responses at 9 months and 72% at 12 months.
Dr. Sundar Jagannath of Mount Sinai, a trial investigator, described the results as “early, deep, and durable,” underscoring the significance for patients with limited options.
Lynozyfic introduces a response-adapted dosing schedule: weekly administration initially, transitioning to biweekly at week 14, and potentially to every four weeks for patients achieving a very good partial response (VGPR) or better after 24 weeks. Hospitalization is required for 24 hours after each of the first two step-up doses to monitor for adverse events.
The drug carries a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity. Common adverse reactions (in ≥20% of patients) include musculoskeletal pain, fatigue, diarrhea, and pneumonia. Grade 3 or 4 lab abnormalities were primarily hematologic.
Beyond R/R MM, Regeneron is exploring Lynozyfic’s use in earlier lines of therapy and in combination regimens. The ongoing Phase Ib LINKER-MM2 and Phase III LINKER-MM3 studies aim to further characterize efficacy and safety across broader patient populations.
