The FDA on Tuesday disputed Regeneron Pharmaceuticals‘ Application for approval of linvoseltamab for the treatment of patients with relapsed or refractory multiple myeloma whose disease has progressed after at least three prior lines of therapy.
In a Complete Response Letter, the regulator pointed to problems at a third-party filling facility during a pre-approval inspection. Regeneron emphasized in its announcement that manufacturing was the “only approval issue” the FDA raised. The agency raised no concerns about linvoseltamab’s efficacy and safety data or Regeneron’s ongoing confirmatory study of the candidate, the company said.
Regeneron stated that the company has since worked with the third-party service provider to address FDA’s concerns and that the fill/finish site now faces another inspection in the coming months.
Tuesday’s rejection came as no surprise to Regeneron. Annual Report for the Second Quarter of 2024 Earlier this month, company officials told investors that the FDA had informed them of the results of its on-site inspection.
“While we believe these findings are now resolved, further review will be required and therefore we expect any potential FDA approval for linvoseltamab will likely be delayed beyond the August 22 PDUFA deadline,” CEO Leonard Schleifer said during a conference call with investors.
Linvoseltamab is a bispecific antibody that targets the BCMA protein and the CD3 antigen. Through this mechanism of action, Linvoseltamab can build a bridge between malignant B cells and cancer-killing T cells, thereby strengthening the body’s own cancer defenses.
Regeneron’s biologics filing for linvoseltamab is based on data from the Phase I/II LINKER-MM1 study, a pivotal dose escalation and dose expansion study of more than 280 patients. In December 2023, the company will shared data The study shows that after eleven months of treatment, there was an objective response rate of 71% and almost half of the patients achieved complete remission or better.
However, the promising efficacy of linvoseltamab has been marred by a high number of safety issues. Results in December 2023 showed that all 117 patients treated with the 200 mg dose of the bispecific antibody experienced adverse reactions, 85% of which were grade 3 or higher. Fourteen patients died due to treatment-related adverse reactions.
In June 2024, Regeneron updated data published of LINKER-MM1, which confirmed the high response rate of linvoseltamab and additionally showed good overall survival and progression-free survival.
In addition to LINKER-MM1, Regeneron is also conducting the Phase III confirmatory study LINKER-MM3, which is designed to evaluate the clinical benefit of linvoseltamab in heavily pretreated patients with relapsed or refractory multiple myeloma. According to its clinicaltrials.gov pageLINKER-MM3 is expected to be completed in 2032.
