Linvoseltamab Wins European Approval Despite FDA Rejection

Regeneron’s bispecific antibody linvoseltamab has received conditional approval from the European Commission (EC) for use in relapsed or refractory multiple myeloma. The decision comes just eight months after the drug was rejected by the FDA due to manufacturing concerns, despite promising clinical data.

New mechanism for relapsed myeloma

Multiple myeloma is the second most common blood cancer worldwide, affecting plasma cells in the bone marrow. Despite significant therapeutic progress over the past two decades, multiple myeloma remains incurable. Most patients experience multiple cycles of remission and relapse, with each recurrence typically leading to shorter and less effective treatment response.

Treatment options become especially limited for patients whose disease no longer responds to the three major drug classes commonly used in multiple myeloma: proteasome inhibitors, immunomodulatory agents and anti-CD38 monoclonal antibodies. For these individuals, new treatments with different mechanisms of action are urgently needed.

“Despite treatment advances, patients with multiple myeloma inevitably endure relapses, reduced responses to subsequent therapies and increasingly shorter remissions,” said Dr. Paula Rodriguez-Otero, a specialist in hematology and hemotherapy at the oncology center of the University of Navarra.

Bispecific antibody molecules are designed to engage T cells and redirect them to kill cancer cells by simultaneously targeting CD3 on T cells and B-cell maturation antigen (BCMA), a protein commonly expressed on multiple myeloma cells.

Regeneron’s linvoseltamab, now branded as Lynozyfic™, joins a growing class of BCMA-targeted therapies, offering less frequent dosing for responders following an initial treatment period.

EC approves Lynozyfic after strong results in LINKER-MM1 trial

The EC granted conditional marketing authorization for linvoseltamab on April 28, 2025, based on findings from the Phase 1/2 LINKER-MM1 trial. The study enrolled 117 patients with relapsed or refractory multiple myeloma who had received at least 3 prior lines of therapy – 87% of patients were refractory to all 3 major classes of myeloma therapy.

At the approved 200 mg dose, the trial reported an objective response rate of 71%, with half of the patients achieving a complete response or better. Among those with a complete response, 41% were minimal residual disease negative. The median duration of response was 29 months, although this figure was not fully estimable for all patients at the time of reporting.

The drug is the first bispecific BCMAxCD3 antibody approved in Europe that allows for dosing every 4 weeks, provided patients have received at least 24 weeks of treatment and achieved a "very good partial response" or better. The initial administration includes two short hospital monitoring periods during the step-up dosing phase.

“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,” said Rodriguez-Otero.

Cytokine release syndrome (CRS) occurred in 46% of patients, though only 1% experienced Grade 3 or higher events. Other frequently reported adverse events included anemia, thrombocytopenia and infections, consistent with the safety profiles of similar agents.

What’s next for Lynozyfic?

With European approval now secured, linvoseltamab provides a new option for patients with triple-class–exposed relapsed or refractory multiple myeloma. Its less frequent, response-adapted dosing schedule may offer practical advantages over other BCMA-targeting bispecific antibodies, particularly for patients with significant disease burden or limited tolerance for continuous therapy.

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“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 Rodriguez-Otero.

While response rates are encouraging, key questions remain about long-term outcomes, safety in broader populations and how the therapy performs outside controlled trial settings. CRS, neutropenia and other immune-mediated effects necessitate close monitoring.

A Phase 3 trial (LINKER-MM3) is underway to confirm efficacy and support full approval.

“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,” said Dr. George D. Yancopoulos, president and chief scientific officer of Regeneron.

Meanwhile, its regulatory fate in the US remains uncertain. The FDA declined the initial application in 2024 due to issues at a third-party manufacturing facility – unrelated to the drug’s clinical performance. Regeneron has since resubmitted the application, with a decision expected by July 2025.

This article is a rework of a press release issued by Regeneron Pharmaceuticals. Material has been edited for length and content.