FDA Sets Review Date for Linvoseltamab for Multiple Myeloma

The FDA has accepted for review the resubmission of Regeneron Pharmaceuticals’ biologics license application (BLA) for linvoseltamab to treat adult patients with relapsed/refractory multiple myeloma. If approved, linvoseltamab would be indicated for those who have received at least four prior lines of therapy or those who received three prior lines of therapy and are refractory to the last line of therapy. The target action date for the FDA decision is July 10, 2025.

Multiple myeloma is an aggressive and incurable blood cancer that affects plasma cells made in the bone marrow. It’s more common among older people; most people diagnosed with multiple myeloma are at least 65 years old. More than 36,000 new cases are expected to be diagnosed this year, and the American Cancer Society predicts there will be about 12,000 deaths in 2025.

While current treatments are able to slow the progression of the cancer, most patients will ultimately experience disease progression and require additional therapies.

Linvoseltamab is a bispecific antibody designed to bridge B-cell maturation antigen on multiple myeloma cells with CD3-expressing T cells.

The BLA is supported by data from the phase 1/2 trial LINKER-MM1 trial. Results from this trial were released in December 2023. At a median duration of follow-up of 11 months where 117 patients received linvoseltamab 200 mg, the objective response rate was 71%, with 46% achieving a complete response or better.

Additionally, 14-month median follow-up data were presented at the European Hematology Association (EHA) Congress 2024 and published in the Journal of Clinical Oncology. These results that the 71% objective response rate was maintained with 50% of patients achieving a complete response or better and 63% achieved a very good partial response or better. The median duration of response was 29 months for all responders. The median overall survival of 31 months for all patients.

In the 14-month follow up study, cytokine release syndrome was the most commonly occurring treatment-emergent adverse event and was observed in 46% of patients; 35% were grade 1 and 10% were grade 2. Infections occurred in 74% of patients and decreased in frequency and severity after 6 months. The most common Grade 3 or 4 treatment-emergent adverse event were neutropenia (42%) and anemia (31%). Six deaths considered due to TEAEs by investigators occurred on treatment or within 30 days of the last treatment dose; five were due to infection, and one was due to renal failure.

The open-label LINKER MM2 study is with 282 enrolled patients. The phase 2 dose expansion portion is assessing the safety and anti-tumor activity of linvoseltamab, with the primary endpoint of objective response rate. A phase 3 confirmatory trial (LINKER-MM3) for linvoseltamab in patients with relapsed/refractory multiple myeloma is ongoing.

Linvoseltamab is also being investigated as a monotherapy and in combination regimens across different lines of therapy in multiple myeloma, including earlier lines of treatment.

Related: FDA Issues Complete Response Letter for Linvoseltamab for Multiple Myeloma

In August 2024, the FDA had issued a complete response letter for linvoseltamab because of issues related to a third-party fill-and-finish manufacturer. During an inspection, the FDA found several unnamed issues, which Regeneron said at the time had been resolved.