FDA Rejects Regeneron's Linvoseltamab Due to Manufacturing Issues

Regeneron Pharmaceuticals has faced a setback in its attempt to gain approval for its multiple myeloma drug candidate, linvoseltamab, from the US Food and Drug Administration (FDA). The FDA declined to approve the biologics licence application (BLA) due to issues identified at a third-party manufacturing site.

The problem was highlighted in a complete response letter (CRL), which Regeneron had anticipated and disclosed in its Q2 financial results. The obstacle pertains to an FDA inspection of a third-party fill/finish manufacturing facility, a stage in drug processing involving packaging for storage and distribution.

Regeneron clarified that the issue was discovered during an FDA inspection conducted for another company's candidate application at the same manufacturing site and has since been resolved. A re-inspection by the FDA is scheduled for the coming months as indicated in Regeneron’s press release on August 20.

Regeneron had submitted the BLA for linvoseltamab under priority review in February this year. Meanwhile, the European Medicines Agency (EMA) is also reviewing linvoseltamab for the same indication, with the application accepted in February. The EMA typically has up to 210 days to evaluate a marketing authorisation.

Linvoseltamab is an investigational bispecific antibody targeted at adults with relapsed or refractory multiple myeloma who have undergone at least three previous therapies. The drug functions by facilitating the interaction between B cell maturation antigen (BCMA) in multiple myeloma cells and CD3-expressing T cells, thereby allowing immune response cells to act on cancer cells.

Regeneron presented data from the Phase I/II LINKER-MM1 study (NCT03761108) at the 2024 EHA Congress in June. The study showed that at a median follow-up of 14.3 months, a 200mg dose of linvoseltamab resulted in an objective response rate (ORR) of 71%, with 50% of patients achieving a complete response (CR) or better.

It is estimated that approximately 35,780 new multiple myeloma diagnoses will be made in the US in 2024, with about 12,500 deaths expected from the disease. According to GlobalData’s Pharma Intelligence Centre, the multiple myeloma market was valued at $15.7 billion in 2023.

This regulatory setback comes at a challenging time for Regeneron as it faces increased competition for its blockbuster ophthalmic drug, Eylea (aflibercept). Eylea, developed jointly with Bayer, generated $5.89 billion in sales last year, but revenues fell by 6.3% due to competition from Roche’s wet AMD drug Vabysmo (faricimab) and others. Biosimilars to Eylea also entered the market in May this year.

Despite this, Regeneron reported positive sales figures for the high-dose version of Eylea. US sales of Eylea HD reached $304 million in Q2 this year, up from $200 million in Q1, providing a boost to the declining Eylea franchise.

The delay in linvoseltamab’s approval is undoubtedly a hurdle for Regeneron, but the company remains committed to addressing the FDA’s concerns and advancing its drug pipeline.