FDA Grants Avidity Fast Track Designation for Experimental FSHD Therapy

The U.S. Food and Drug Administration granted Avidity Biosciences Fast Track designation to its AOC 1020, an experimental antibody oligonucleotide conjugate in development to treat the rare neuromuscular condition facioscapulohumeral muscular dystrophy.

Photo: Steve Hughes, chief medical officer at Avidity

Facioscapulohumeral muscular dystrophy (FSHD) is a rare, hereditary muscle-weakening condition marked by life-long, progressive loss of muscle function that causes significant pain, fatigue, and disability. FSHD is characterized by progressive and often asymmetric skeletal muscle loss that typically causes weakness initially 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. The abnormal expression of DUX4 gene leads to a series of downstream events that result in skeletal muscle wasting and progressive loss of 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 many people affected by FSHD to become dependent on the use of a wheelchair for mobility. Currently, there are no approved treatments for people living with FSHD.

AOC 1020 is designed to treat the underlying cause of FSHD. The abnormal expression of DUX4 protein leads to changes in gene expression in muscle cells that are associated with the life-long, progressive loss of muscle function in patients with FSHD. AOC 1020 aims to reduce the expression of DUX4 mRNA and DUX4 protein in muscles in patients 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.

AOC 1020 is being studied in the Phase 1/2 FORTITUDE clinical trial in adults with FSHD and is the company’s second muscle-targeting small interfering RNA AOC in clinical development. Avidity plans to share data from a preliminary assessment of AOC 1020 in approximately half of study participants from the FORTITUDE trial in the first half of 2024.

Fast Track designation enables more frequent interactions with the FDA to expedite the development and review process for drugs intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. Currently, there are no FDA-approved treatments for people living with FSHD.

“The FDA Fast Track designation for AOC 1020 reinforces the importance of finding an effective treatment to help people living with FSHD, a devastating and debilitating muscular dystrophy disorder with no treatment options,” said Steve Hughes, chief medical officer at Avidity. “AOC 1020 is designed to directly target the disease-causing gene, DUX4, to address the underlying cause of FSHD. We look forward to working collaboratively with the FDA to bring the first RNA therapy directly targeting DUX4 to patients as quickly as possible.”

Author: Rare Daily Staff