Reduction of DUX4 for the Treatment of Facioscapulohumeral Muscular Dystrophy (FSHD) with FTX-1821

Diego Cadavid
Fulcrum Therapeutics

July 2018

Fulcrum is developing small molecules that modulate targets responsible for regulating gene expression.  Fulcrum plans to submit regulatory filings in early 2019 for lead compound FTX-1821 to treat facioscapulohumeral muscular dystrophy (FSHD), a disease caused by dysregulated expression of double homeobox 4 (DUX4). Unpublished in vitro data show FTX-1821 inhibits DUX4 expression, prevents cell death and restores function in muscle cells from FSHD patients. TACT reviewed Fulcrum’s proposal for its lead program to treat FSHD with FTX-1821 via the reduction of DUX4. The committee felt that this was a well thought out plan with a number of de-risking activities already in place or underway to evaluate and standardize drug development tools and assessments prior to initiating the clinical trials.  The committee made a number of recommendations regarding the interpretation of the preclinical data, design of the proof of concept clinical trial and considerations for go/no-go decisions prior to and after the proof of concept clinical trial.

17 Dec 2018