Initiation of Biomarker Cohort in Clinical Trial for Facioscapulohumeral Muscular Dystrophy

Steve Hughes, MD, Chief Medical Officer of Avidity Biosciences, discusses the initiation of a biomarker cohort in the Phase 1/2 FORTITUDE trial of delpacibart braxlosiran (del-brax) in patients with facioscapulohumeral muscular dystrophy (FSHD).

FSHD is a disorder characterized by muscle weakness and atrophy. This condition gets its name from the areas of the body that are affected most often: muscles in the face (facio-), shoulder blades (scapulo-), and upper arms (humeral). The signs and symptoms of FSHD usually appear in adolescence. FSHD results from a deletion of genetic material from a region of DNA known as D4Z4.

The FORTITUDE study is a phase 1/2 randomized, placebo-controlled, double-blind clinical trial evaluating the dosing, safety, tolerability, and pharmacokinetics of del-brax in patients with FSHD. Key biomarkers in this study include DUX4-regulated muscle and circulating biomarkers as well as MRI measures of muscle volume and composition. An open-label extension study will follow the completion of the FORTITUDE trial.

The biomarker cohort in the FORTITUDE trial will assess the impact of del-brax 2 mg/kg every six weeks in people living with FSHD, ages 16-70. The primary endpoints of the study are changes in DUX4 regulated gene expression and DUX4 regulated circulating biomarker.

Del-brax is an investigational monoclonal antibody that binds to the transferrin receptor 1 and targets the DUX4 gene. In initial data, del-brax at a dose of 2 mg/kg every six weeks illustrated significant and consistent reductions in DUX4 regulated genes, decreases in novel circulating biomarker and creatine kinase, and functional improvement at month four.