FDA Issues Complete Response Letter for Linvoseltamab for Multiple Myeloma

The FDA has issued a complete response letter (CRL) for the Regeneron’s biologics license application (BLA) for linvoseltamab to treat patients with relapsed/refractory multiple myeloma.

During an inspection FDA found issues at a third-party fill/finish manufacturer, which Regeneron indicated have been resolved. Regeneron hasn’t said what those issues were. The facility is awaiting reinspection by the FDA, and this is expected to take place in the coming months.

Multiple myeloma is an aggressive and incurable blood cancer that affects plasma cells made in the bone marrow. More than 35,000 new cases of multiple myeloma are diagnosed annually in the United States. 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 a phase 1/2 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.

In June 2024, the 14-month median follow-up data were presented at the European Hematology Association (EHA) Congress 2024 and published in the Journal of Clinical Oncology.

From the 14 month data, the objective response rate was 71% with 50% of patients achieving a complete response or better and 63% achieving a very good partial response or better. Median duration of response of 29 months for all responders, and the median overall survival of 31 months for all patients.

Safety data at the 14-month median follow-up was generally consistent with the 11-month median follow-up. Cytokine release syndrome was the most common treatment-emergent adverse event, seen in 46% of patients.

The most common grade 3 or 4 treatment-emergent adverse events were neutropenia (42%) and anemia (31%). Six deaths considered due to adverse events occurred while on treatment or within 30 days of the last treatment dose; five were due to infection, and one was due to renal failure.

A phase 3 confirmatory trial in patients with relapsed/refractory multiple myeloma is continuing.