Investigational Therapy for Facioscapulohumeral Muscular Dystrophy Shows Promise According to Avidity Biosciences

Initial 4-month results from the phase 1/2 FORTITUDE clinical trial (NCT05747924) reveal that treatment of people with facioscapulohumeral muscular dystrophy (FSHD) using AOC 1020 (delpacibart braxlosiran [del-brax]; Avidity Biosciences, San Diego, CA) is associated with functional improvement and reductions in abnormal gene expression, as well as favorable safety and tolerability. The findings were presented at the 31st Annual FSHD Society International Research Congress.

AOC 1020 is part of a new class of therapies called antibody oligonucleotide conjugates (AOCs), which combine the benefits of monoclonal antibody (mAb) therapies with those of oligonucleotides to address the underlying causes of disease. In the case of FSHD, AOC1020 is designed to target the abnormal expression of the double homeobox 4 (DUX4) gene associated with the downstream skeletal muscle wasting and compromised muscle function that characterize the disease.

FORTITUDE is a randomized, placebo-controlled, double-blind clinical trial evaluating single and multiple doses of AOC 1020 as a treatment for 39 adult participants with FSHD. The primary outcomes are safety and tolerability, with additional endpoints assessing the investigational therapy’s activity as defined by biomarker measurements.

Avidity Biosciences reported initial 4-month data from 12 participants in the 2 mg/kg dose cohort:

• DUX4regulated gene expression in muscle showed mean reductions >50% across multiple panels.
• All participants treated with AOC 1020 showed >20% reductions of DUX4regulated genes.
• Participants showed ≥25% reductions in levels of novel circulating biomarkers and creatine kinase.
• Participants showed functional improvement trends, including increased upper and lower limb muscle strength and muscle function, compared to placebo and the ReSolve natural history study.
• Patient and clinician reported outcomes showed trends of improvement.

Additionally, participants showed favorable safety and tolerability. All adverse events (AEs) were mild or moderate, with no serious AEs or discontinuations.

"As the first therapy to directly target DUX4, it is very encouraging to see that the del-brax data demonstrate consistent reductions in DUX4 regulated genes and provided trends of functional improvement in patients with FSHD at the four-month timepoint. These early data would support the notion that del-brax has the potential to change the course of disease for people living with FSHD," said Jeffrey M. Statland, MD, FORTITUDE Trial Investigator.