Increases in Skin FXN as Evidence of Effectiveness: FDA recommended focusing on assessments of skin FXN concentrations rather than buccal FXN concentrations due to more consistent sampling and less variability. FDA acknowledged that recently submitted data appear to support a relationship between increased FXN concentrations in skin cells and relevant tissues such as the heart, dorsal root ganglion and skeletal muscle. FDA also acknowledged that the nonclinical studies were performed at relevant human doses.
FDA also suggested that Larimar consider exploring the relationship between increases in FXN in skin and changes in pharmacodynamic markers such as lipid profiles and/or clinical measures to provide additional support for the use of FXN as a RLSE.
BLA Submission and Initiation of Global Phase 3 Study on Track: Larimar has obtained feedback from both FDA and EMA on the global Phase 3 study protocol and is on track to initiate the study by mid-2025 with potential sites in the U.S., Europe, U.K., Canada, and Australia. Larimar is targeting the BLA submission to seek accelerated approval by the end of 2025.
