Novo Nordisk's Once-Weekly Insulin Icodec Receives FDA Complete Response Letter

▎Armstrong

On July 10, 2024, Novo Nordisk announced that it had received a Complete Response Letter from the FDA regarding the marketing application for once-weekly insulin Icodec. The FDA's requests mainly concern manufacturing processes and the Type 1 diabetes indication. Novo Nordisk is in close communication with the FDA to meet these requirements but anticipates that this will not be completed within this year.

IcodecMolecular design isRemove insulin B30 and simultaneously introduce four amino acid mutations: A14E, B16H, B25H, and B29K. Attach a C20 fatty acid chain to B29K. Compared to insulin detemir and insulin degludec (conjugated with C14 and C16 respectively),Icodec has a stronger ability to bind with albumin, thereby achieving a longer half-life.The purpose of the A14E, B16H, and B25H mutations is to reduce enzymatic degradation while decreasing affinity for the insulin receptor (IR), minimizing IR-mediated clearance, and further prolonging the half-life.

Summary

Icodec has been approved for marketing in Europe, China, and other regions. Previously, the FDA advisory committee mainly discussed the risk of hypoglycemia associated with the type 1 diabetes indication. Although the specific reasons were not disclosed in this Complete Response Letter (CRL), it also mentioned the type 1 diabetes indication. Additionally, production issues were raised.