Linvoseltamab Gains FDA Pathway After Manufacturing Hurdle Resolution; Decision Timeline Extends to Mid-2025

Regeneron Pharmaceuticals has reached a milestone in its pursuit of regulatory approval for linvoseltamab, a bispecific antibody candidate designed to combat one of blood cancer’s most persistent challenges: relapsed and refractory multiple myeloma. The FDA has now formally accepted the resubmitted Biologics License Application, with a decision target set for July 10, 2025.

The Manufacturing Challenge Behind the Approval Path

The resubmission comes after Regeneron successfully resolved third-party fill/finish manufacturing complications—the primary issue flagged by regulators in the prior submission attempt. This resolution paves the way for the agency’s full review of linvoseltamab’s clinical evidence package, particularly data from the pivotal LINKER-MM1 trial.

Understanding the Patient Population and Disease Burden

Multiple myeloma remains the second most common blood cancer globally, with over 187,000 new diagnoses annually. In the United States alone, the 2025 projections indicate more than 36,000 new cases and approximately 12,000 deaths. A particularly vulnerable subset includes roughly 8,000 Americans whose disease has progressed beyond three treatment lines, plus an additional 4,000 whose myeloma has continued advancing even after four or more prior therapies.

The disease devastates patients through unchecked proliferation of malignant plasma cells that accumulate in bone marrow, crowd out healthy blood production, infiltrate adjacent tissues, and trigger organ damage. Despite therapeutic advances, multiple myeloma remains incurable, and current treatments typically slow—rather than halt—disease progression, eventually necessitating additional interventions.

How Linvoseltamab Works: Mechanism and Clinical Design

Linvoseltamab operates as a BCMAxCD3 bispecific antibody, functioning as a biological bridge that connects two critical elements: B-cell maturation antigen (BCMA) present on malignant myeloma cells and CD3 receptors on T cells. This connection activates the patient’s own immune T cells to recognize and destroy cancer cells more effectively.

The ongoing LINKER-MM1 trial represents an extensive clinical investigation enrolling 282 patients with relapsed or refractory multiple myeloma across multiple centers. The now-completed Phase 1 dose-escalation portion systematically evaluated safety, tolerability, and dose-limiting toxicities across nine escalating dose levels, exploring diverse administration approaches.

The Phase 2 dose-expansion phase continues to evaluate linvoseltamab’s safety profile and anti-tumor effectiveness, with objective response rate as the primary measure of success. Secondary endpoints include duration of sustained response, progression-free survival duration, achievement of minimal residual disease negativity, and overall survival duration.

Treatment Administration and Patient Considerations

Patients in the Phase 2 cohort must have previously received at least three prior treatment lines or demonstrated triple-class refractoriness. The linvoseltamab dosing strategy employs an initial step-up regimen leading to a standard 200 mg weekly dose. At week 16, all patients transition to biweekly administration. An adaptive response-based approach allows patients demonstrating very good partial response or superior outcomes—after completing at least 24 weeks of therapy—to further space dosing to every four weeks. The regimen necessitates two 24-hour hospitalizations for intensive safety monitoring.

Broader Clinical Development Trajectory

Beyond the LINKER-MM1 monotherapy investigation, Regeneron is pursuing a comprehensive clinical strategy exploring linvoseltamab in multiple combinations with other anticancer agents (Phase 1b LINKER-MM2 trial) and as monotherapy in a Phase 3 confirmatory trial (LINKER-MM3). Additional studies evaluate its potential in earlier treatment lines and in plasma cell precursor conditions.

Regulatory Review Timeline and European Status

With the FDA acceptance confirmed, the agency’s substantive review proceeds toward the July 10, 2025 decision target. Simultaneously, linvoseltamab undergoes parallel regulatory evaluation by the European Medicines Agency for the same patient population, offering potential for expanded access if approval pathways succeed on both sides of the Atlantic.