Avidity Biosciences has initiated enrollment for Cohort C of its Phase 1/2 FORTITUDE clinical trial, which is evaluating the investigational therapy delpacibart braxlosiran (del-brax, formerly AOC 1020) in individuals living with facioscapulohumeral muscular dystrophy (FSHD). This advancement marks a significant step in the development of a potential treatment for this rare genetic disorder characterized by progressive muscle weakness.
The biomarker cohort (Cohort C) will assess the safety and efficacy of del-brax at a dose of 2 mg/kg, administered every six weeks, in patients aged 16-70. The primary focus will be on measuring changes in DUX4-regulated biomarkers, which are central to the pathogenesis of FSHD. Enrollment is expected to be completed in the first half of 2025, and the cohort study will be conducted in the US, Canada, and the UK, mirroring the locations of Cohorts A and B.
Targeting the Root Cause of FSHD
Del-brax is designed to address the underlying cause of FSHD by targeting the DUX4 gene, which is abnormally expressed in individuals with the condition. By reducing the expression of DUX4, the therapy aims to alleviate the downstream effects that lead to muscle degeneration and weakness. Currently, there are no approved treatments specifically targeting the root cause of FSHD, highlighting the significant unmet medical need.
"We are advancing our clinical studies for del-brax as quickly as possible as we understand the urgency to bring a potential new treatment to people living with FSHD," stated The Avidity Team in a letter to the FSHD community.
Promising Initial Data
Initial data from the FORTITUDE trial has demonstrated encouraging results. Del-brax has shown reductions in DUX4 regulated genes, decreases in novel circulating biomarkers, and creatine kinase, along with trends of functional improvement at the four-month mark. The therapy has also exhibited a favorable safety and tolerability profile. These findings were presented at the 31st Annual FSHD Society International Research Congress.
The FORTITUDE trial is a randomized, placebo-controlled, double-blind study designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of del-brax. The trial also includes an open-label extension study, FORTITUDE-OLE, for long-term evaluation of the drug's safety and tolerability.
Regulatory Designations and Future Plans
Del-brax has received Orphan designation from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), as well as Fast Track designation from the FDA. Avidity anticipates initiating a larger functional cohort of the FORTITUDE trial in the first half of 2025, potentially expanding the trial to additional countries.
Avidity is in continuous engagement with the FDA about a path forward, but it is too early to speculate about a potential approval.
