Lynozyfic (linvoseltamab) approved in the European Union for the treatment of relapsed/refractory multiple myeloma - Regeneron

Regeneron Pharmaceuticals, Inc. announced 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). 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.