Delpacibart Braxlosiran in Patients With Facioscapulohumeral Muscular Dystrophy

Mike Flanagan, PhD, Chief Scientific Officer at Avidity Biosciences, discusses topline results from study testing delpacibart braxlosiran (del-brax) in patients with facioscapulohumeral muscular dystrophy and the newly initiated phase 3 trial. FSHD is a rare 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, around the shoulder blades, and in the upper arms. The signs and symptoms of FSHD usually appear in adolescence and include loss of muscle function, pain, and fatigue. The condition is caused by abnormal expression of the DUX4 gene. Del-brax is a monoclonal transferrin receptor 1 (TfR1) antibody conjugated with a siRNA targeting DUX4 mRNA, designed to target the underlying cause of abnormal DUX4 gene expression. The FORTITUDE clinical trial program includes a phase 1/2, randomized, placebo-controlled, double-blind study evaluating multiple doses of del-brax in patients with FSHD. In total, the two dose escalation cohorts evaluated 39 patients on either 2 mg/kg or 4 mg/kg of del-brax versus placebo over 12 months. Top line data from this trial showed consistent improvement of functional mobility and muscle strength measured by the 10-Meter Walk-Run test, Timed Up and Go, and quantitative muscle testing compared to placebo. There was also an observed consistent improvement in multiple measures of quality of life with del-brax versus placebo measured by patient reported outcomes. Additionally, rapid and significant reductions in KHDC1L and creatine kinase levels were observed. Del-brax is illustrating a favorable long-term safety and tolerability profile with most adverse events mild to moderate. Based on these results, del-brax has been granted access to the Accelerated Approval Program for the treatment of FSHD by the U.S. Food and Drug Administration (FDA). To move forward with a full approval, the global, confirmatory, randomized, placebo-controlled, double-blind, 18-month, phase 3 FORWARD study has been initiated. The study will evaluate 2 mg/kg of del-brax every six weeks in approximately 200 patients with FSHD. Chapters: Introduction 00:00 FSHD Overview 00:48 Current Management 4:11 Del-brax Overview 4:38 FORTITUDE Clinical Trial Data 5:43 Next Steps 6:56 Other Programs 8:14