Avidity Biosciences Granted FDA Fast Track Designation for the Treatment of Facioscapulohumeral Muscular Dystrophy

Avidity Biosciences, Inc. recently announced the US FDA has granted Fast Track designation to AOC 1020 for the treatment of facioscapulohumeral muscular dystrophy (FSHD). FSHD is a serious, rare, hereditary muscle-weakening condition marked by life-long, progressive loss of muscle function that causes significant pain, fatigue, and disability. 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 (siRNA) 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, MD, 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.”

Avidity’s proprietary AOCs are designed to combine the specificity of monoclonal antibodies (mAbs) with the precision of oligonucleotide therapies to target the root cause of diseases previously untreatable with RNA therapeutics. AOC 1020 consists of a proprietary mAb that binds to the transferrin receptor 1 (TfR1) conjugated with a siRNA targeting double homeobox 4 (DUX4) mRNA. 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.

Avidity has three distinct rare disease programs in the clinic. In addition to AOC 1020, the company is also evaluating AOC 1001 in the Phase 1/2 MARINA and MARINA open-label extension (MARINA-OLE) clinical trials for the treatment of myotonic dystrophy type 1 (DM1) and AOC 1044 in the Phase 1/2 EXPLORE44 trial for the treatment of Duchenne muscular dystrophy (DMD) mutations amenable to exon 44 skipping (DMD44).

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.

Facioscapulohumeral muscular dystrophy (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 (double homeobox 4) 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, which is caused by the abnormal expression of a gene called double homeobox 4 or DUX4. 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.

Avidity Biosciences, Inc.’s mission is to profoundly improve people’s lives by delivering a new class of RNA therapeutics – Antibody Oligonucleotide Conjugates (AOCs). Avidity’s proprietary AOCs are designed to combine the specificity of monoclonal antibodies with the precision of oligonucleotide therapies to target the root cause of diseases previously untreatable with RNA therapeutics. Avidity’s advancing and expanding pipeline has three programs in clinical development. AOC 1001 is designed to treat people with myotonic dystrophy type 1 (DM1) and is currently in Phase 1/2 development with the ongoing MARINA and MARINA-OLE trials. AOC 1020 is designed to treat people living with facioscapulohumeral muscular dystrophy (FSHD) and is currently in Phase 1/2 development with the FORTITUDE trial. AOC 1044 is designed for people with Duchenne muscular dystrophy (DMD) mutations amenable to exon 44 skipping and is currently in Phase 1/2 development with the EXPLORE44 trial. AOC 1044 is the first of multiple AOCs the company is developing for DMD. Avidity is also broadening the reach of AOCs beyond muscle tissues through both internal discovery efforts and key partnerships as the company continues to deliver on the RNA revolution. Avidity is headquartered in San Diego, CA. For more information, visit www.aviditybiosciences.com.