Avidity Reveals Groundbreaking AOC 1020 Data from Phase 1/2 FORTITUDE™ Trial with Over 50% Reduction in DUX4 Genes & Functional Improvement in FSHD Patients

Avidity Biosciences, Inc., a biopharmaceutical company specializing in RNA therapeutics called Antibody Oligonucleotide Conjugates (AOCs™), has revealed promising initial data from its Phase 1/2 FORTITUDE™ trial. The trial evaluates Avidity's investigational therapy, delpacibart braxlosiran (del-brax, also known as AOC 1020), designed to address the underlying cause of facioscapulohumeral muscular dystrophy (FSHD). The findings showed over 50% reduction in DUX4 regulated genes, along with trends indicating functional improvement and favorable safety and tolerability.

FSHD is a rare inherited disorder characterized by progressive muscle weakness, pain, and disability. It is caused by the abnormal expression of the DUX4 gene, leading to muscle deterioration. Currently, there are no approved treatments for FSHD. Del-brax is the first therapy aimed directly at the root cause of this condition by targeting and reducing DUX4 gene expression.

The FORTITUDE™ trial's initial data is especially significant because it shows not only genetic impact but also potential functional benefits. Jeffrey M. Statland, M.D., Professor of Neurology at the University of Kansas Medical Center and a trial investigator, highlighted the promising nature of these early results. He noted that del-brax could alter the disease's progression by improving muscle strength and function, which could benefit patients grappling with this debilitating condition.

The trial's data will be presented at the 31st Annual FSHD Society International Research Congress in Denver, Colorado. The four-month assessment of del-brax covered 39 participants across two dosage levels (2 mg/kg and 4 mg/kg). Participants in the 2 mg/kg cohort saw significant reductions in DUX4 regulated genes and biomarkers, alongside improvements in muscle strength and function. Importantly, the therapy demonstrated a favorable safety profile, with all adverse events being mild or moderate and no serious adverse events or discontinuations.

Sarah Boyce, President and CEO of Avidity, emphasized the urgency of developing a treatment for FSHD, given the lack of current options. She expressed confidence in del-brax's potential to be a first-in-class therapy, capable of transforming the lives of FSHD patients. This therapy represents Avidity's third rare muscle disease program to show promise in muscle delivery and target engagement, reinforcing the potential of their AOC platform.

The FORTITUDE™ trial is a randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of del-brax in adult FSHD patients. The primary goal is to assess del-brax's safety and tolerability, with secondary measures including biomarker activity and functional assessments of muscle strength and mobility.

Del-brax works by targeting the abnormal expression of the DUX4 gene in skeletal muscle, which is responsible for the muscle-wasting effects seen in FSHD. The therapy involves a monoclonal antibody linked to siRNA, which specifically targets and reduces DUX4 mRNA and protein levels in muscle cells. Preclinical studies have shown that del-brax can prevent muscle weakness and improve muscle function.

FSHD is a progressive and often asymmetrical muscle-wasting condition with no approved treatments. It affects skeletal muscles, leading to significant physical limitations, pain, and fatigue. Patients often lose the ability to perform basic tasks, including lifting their arms or smiling, and many eventually require wheelchairs for mobility.

Avidity Biosciences aims to transform the field of RNA therapeutics with its AOCs, which combine the targeting ability of monoclonal antibodies with the precision of oligonucleotide therapies. Their pipeline includes programs for myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD), and FSHD, with potential applications in cardiology and immunology as well.