The U.S. FDA has issued a complete response letter for Regeneron's BLA for linvoseltamab in relapsed/refractory multiple myeloma that has progressed after at least three prior therapies, citing inspection issues at a third-party facility.
The news did not come as a surprise to Regeneron, who had revealed the anticipated delay during its second quater earnings call earlier in August. According to Regeneron, the FDA had informed the company that the third-party fill-finish manufacturer for linvoseltamab had unresolved findings from a pre-approval inspection for another company's drug candidate.
Now, according to Regeneron, the third-party fill-finish manufacturer has informed the company that it believes the findings have been resolved and their facility is awaiting reinspection by the FDA in the coming months.
Targeting the second most common blood cancer, linvoseltamab is an investigational bispecific antibody designed to bridge B-cell maturation antigen on multiple myeloma cells with CD3-expressing T-cells to facilitate T-cell activation and cancer-cell killing. The FDA had accepted the drug for priority reviw back in February giving it an original PDUFA date of August 22.
Regulatory review of linvoseltamab remains ongoing by the EMA in the same indication.
The CRL comes as part of frustrating trend of FDA rejections based on issues at third-party manufacturing facilities. Last year, the FDA hit Regeneron with a CRL for its 8 mg dose of blockbuster med Eylea "solely due to an ongoing review of inspection findings at a third-party filler," which was later revealed to be Catalent.
In June, AbbVie revealed that it was handed a second CRL for its blockbuster-hopeful treatment of motor fluctuations in advanced Parkinson's disease, this time for observations that were identified during inspection of a CDMO listed in the company's NDA for foscarbidopa/foslevodopa. Just days later, Daiichi Sankyo and Merck & Co. came forward and said the FDA had issued a CRL for their jointly developed ADC, patritumab deruxtecan (HER3-DXd) — again, in response to findings from an inspection of a third-party manufacturing facility.
