Facioscapulohumeral Muscular Dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive and variable hereditary muscle-weakening condition marked by significant pain, fatigue, and disability. It is one of the most common forms of muscular dystrophy, with onset typically in teens and young adults. FSHD affects approximately 16,000 to 38,000 people in the U.S. alone. There are currently no approved therapies to treat the underlying cause of FSHD. Current treatment approaches are focused on support for activities of daily living and mobility, improved functioning and lowering the risk of complications. They include physical therapy, exercise, pain management and orthopedic interventions.

FSHD is characterized by progressive and often asymmetric skeletal muscle loss that initially causes weakness in muscles in the face, shoulders, arms and trunk and progresses to weakness in muscles in the lower body. FSHD is an autosomal dominant genetic disease caused by the abnormal expression of the DUX4 (double homeobox 4) gene primarily in the skeletal muscle. The abberant expression of the DUX4 activates genes that are toxic to muscle cells and leads to a series of downstream events that result in skeletal muscle wasting and compromised muscle function, including an inability to lift arms for more than a few seconds, loss of ability to show facial expressions, and serious speech impediments. These symptoms cause nearly 20% of people affected by FSHD to become dependent on the use of a wheelchair for mobility by age 50.

FSHD Disease Process:

FSHD is caused by the abnormal expression of the DUX4 gene. AOC 1020 is designed to reduce DUX4 and address the cause of FSHD

AOC 1020

We are developing AOC 1020 to treat the underlying cause of FSHD, which is the abnormal expression of the DUX4 gene. AOC 1020 aims to reduce the expression of DUX4 mRNA and DUX4 protein in muscles in people with FSHD. AOC 1020 consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a siRNA targeting DUX4 mRNA. In preclinical studies, a single intravenous dose with the murine version of AOC 1020 prevented development of muscle weakness demonstrated by three functional assays – treadmill running, in vivo force and compound muscle action potential. AOC 1020 is currently in Phase 1/2 development as part of the FORTITUDE™ trial in adults with FSHD. Avidity plans to report preliminary data in approximately half of participants in the FORTITUDE trial in the second quarter of 2024. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) Orphan designation for AOC 1020 and the FDA has granted AOC 1020 Fast Track designation.

The FORTITUDE™ trial is a randomized, placebo-controlled, double-blind, Phase 1/2 clinical trial designed to evaluate AOC 1020 in approximately 70 adult participants with FSHD. FORTITUDE will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AOC 1020 administered intravenously, with the primary objective being the safety and tolerability of AOC 1020 in FSHD patients. Activity of AOC 1020 will be assessed using key biomarkers, including magnetic resonance imaging (MRI) measures of muscle volume and composition. Though the Phase 1/2 trial is not statistically powered to assess functional benefit, it will explore the clinical activity of AOC 1020 including measures of mobility and muscle strength as well as patient reported outcomes and quality of life measures. Participants will have the option to enroll in an open-label extension study at the end of the treatment period in the FORTITUDE study. For more information on this study click here or visit http://www.clinicaltrials.gov and search for NCT05747924.