On April 28, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the European Commission (EC) has granted conditional marketing approval of Lynozyfic (linvoseltamab) to treat adults with relapsed and refractory (R/R) multiple myeloma (MM) (Press release, Regeneron, APR 28, 2025, View Source [SID1234652246]). The indication is specific to those who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy. Lynozyfic is a 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.
Lynozyfic is the first BCMAxCD3 therapy approved that can be dosed every four weeks due to a response-adapted regimen if a very good partial response (VGPR) or better is achieved following completion of at least 24 weeks of therapy. The regimen includes monitoring in close proximity of a qualified treatment center for safety during the step-up dosing period (one 24-hour period after the first step-up dose and another 24-hour period after the second step-up dose, if certain safety events occur).
"Despite treatment advances, patients with multiple myeloma inevitably endure relapses, reduced responses to subsequent therapies, and increasingly shorter remissions. For those who develop relapsed and refractory disease after having been exposed to the three major drug classes, it’s important to have new therapies with different mechanisms of action like linvoseltamab," said Paula Rodriguez-Otero, M.D., Department of Hematology, Cancer Center Clínica Universidad de Navarra, Pamplona, Navarra, Spain. "In a clinical trial, linvoseltamab demonstrated compelling and impressive efficacy with the potential for complete remission in this patient population, including those with high disease burden. Furthermore, its response-adapted schedule will provide patients a convenient treatment option."
The EC approval is based on results from the pivotal LINKER-MM1 trial (n=117 at the 200 mg dose of Lynozyfic), which demonstrated robust and durable responses in patients with R/R MM. Results showed a 71% objective response rate (ORR), with 50% of patients achieving a complete response (CR) or better, as determined by an independent review committee. The minimal residual disease (MRD) negativity rate in patients achieving a CR or stringent CR was 41% (24 of 58 patients; 95% confidence interval [CI]: 29 to 55). The median duration of response (DOR) was 29 months (95% CI: 19 to not estimable).
The most frequent adverse reactions were musculoskeletal pain (52%), cytokine release syndrome (CRS; 46%), neutropenia (43%), cough (42%), diarrhea (39%), anemia (38%), fatigue (36%), pneumonia (32%), and upper respiratory tract infection (30%). The majority of CRS cases were Grade 1 (35%) or Grade 2 (10%), and there was one case of Grade 3 CRS (0.9%) and no cases of ≥Grade 4 CRS. The median time to first CRS onset was 11 hours (range: -1.1 to 184 hours), with the median time to resolution within 1 day (16 hours; range: 1-96 hours). Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS; 2.6%) and infections that were Grade 3 or 4 (36%) or fatal (4%) also occurred.
"Lynozyfic is our second approved bispecific antibody – in this case for relapsed/refractory multiple myeloma patients – reinforcing our relentless commitment to transforming cancer care for those who need it most," said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer of Regeneron. "We are excited by the potential of Lynozyfic and its differentiated clinical profile, dosing and administration. Given the strength of the data, we are pursuing a robust clinical development program exploring its use – in earlier lines of therapy as monotherapy and in novel combinations – with the hope of further advancing care for patients."
In the U.S., the FDA accepted for review the Biologics License Application for linvoseltamab in adults with R/R MM with a target action date of July 10, 2025.
About Multiple Myeloma
As the second most common blood cancer, there are over 35,000 new cases of MM diagnosed in Europe and 187,000 new cases of MM diagnosed globally every year. The disease is characterized by the proliferation of cancerous plasma cells (MM cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. Despite treatment advances, MM is not curable and while current treatments are able to slow the progression of the cancer, most patients will ultimately experience cancer progression and require additional therapies.
About the Lynozyfic (linvoseltamab) Clinical Development Program
Lynozyfic as monotherapy is indicated for the treatment of adult patients with R/R MM who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy. For complete product information, please see the Summary of Product Characteristics that can be found on www.ema.europa.eu in due course.
The ongoing, open-label, multicenter Phase 1/2 dose-escalation and dose-expansion LINKER-MM1 trial is investigating linvoseltamab in more than 300 enrolled patients with R/R 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 ORR. Key secondary endpoints include DOR, progression-free survival, rate of MRD negative status and overall survival.
Eligibility in the Phase 2 portion requires patients to have received at least three prior lines of therapy or have triple-class refractory MM. Linvoseltamab is administered with an initial step-up dosing regimen followed by the full 200 mg dose administered weekly. After week 14, all patients transition to every two-week dosing. A response-adapted regimen further enables patients to shift to every four-week dosing if they achieve a VGPR or better and have completed at least 24 weeks of therapy. The regimen requires a total of two 24-hour hospitalizations for safety monitoring.
Linvoseltamab is being investigated in a broad clinical development program exploring its use as a monotherapy as well as in combination regimens across different lines of therapy in MM, including earlier lines of treatment, as well as plasma cell precursor disorders. They include evaluating linvoseltamab in a Phase 1b trial (LINKER-MM2) in combination with other cancer treatments in R/R MM as well as a Phase 3 confirmatory trial (LINKER-MM3) as a monotherapy in R/R MM. For more information on Regeneron’s clinical trials in blood cancer, visit the clinical trials website, or contact via [email protected] or 844-734-6643.