Dabocemagene Autoficel (D-Fi/FCX-007): An Investigational Gene Therapy for Dystrophic Epidermolysis Bullosa

1. Executive Summary

Dabocemagene autoficel, also known as D-Fi and FCX-007, is an investigational ex vivo, autologous cell-based gene therapy developed by Castle Creek Biosciences Inc. It is designed to treat Dystrophic Epidermolysis Bullosa (DEB), a group of severe inherited skin disorders characterized by extreme skin fragility and blistering. The therapy involves genetically modifying a patient's own dermal fibroblasts using a lentiviral vector to express functional type VII collagen (COL7), the protein deficient in DEB. This approach aims to restore anchoring fibril formation at the dermal-epidermal junction, thereby improving wound healing and skin integrity.[1]

Early-phase clinical trials provided initial positive signals regarding COL7 expression and wound healing.[4] However, the clinical development program faced a significant setback when a pivotal Phase 3 trial (DeFi-RDEB, NCT04213261) was terminated in 2023 due to the unavailability of the lentiviral vector, leading to a period where development appeared stalled.[6] Despite this challenge, the program has demonstrated notable resilience. In early 2025, Castle Creek Biosciences secured $75 million in royalty financing, primarily to support a renewed Phase 3 effort for D-Fi.[5] This financial backing has enabled the initiation of a new Phase 3 study, NCT06892639, which commenced recruitment in March 2025.[1] This sequence of events, from a critical manufacturing-related trial failure to substantial new investment and the launch of a new pivotal study, highlights both the inherent complexities in gene therapy development, particularly concerning viral vector supply chains, and a persistent conviction in the therapeutic potential of dabocemagene autoficel.