Avidity Biosciences Seeks Fast-Track Approval with New Biomarker Cohort for Delpacibart Braxlosiran in FORTITUDE™ Trial for FSHD

Avidity Biosciences, Inc., a biopharmaceutical company, has announced the launch of a biomarker cohort in its Phase 1/2 FORTITUDE trial for delpacibart braxlosiran (del-brax/AOC 1020). This trial, which targets individuals with facioscapulohumeral muscular dystrophy (FSHD), is expected to complete enrollment for the biomarker cohort in the first half of 2025. The company also plans to initiate a functional cohort in the same timeframe. Additionally, the enrollment for the FORTITUDE Open-label Extension study is ongoing.

Del-brax is pioneering as the first therapy designed to treat FSHD by targeting the disease-causing gene, double homeobox 4 (DUX4). FSHD is a rare, hereditary disorder characterized by progressive muscle loss, pain, fatigue, and disability. There are currently no approved treatments for this debilitating condition.

The biomarker cohort will monitor the impact of administering 2 mg/kg of del-brax every six weeks in individuals aged 16-70 living with FSHD. The primary goals are to observe changes in DUX4-regulated gene expression and circulating biomarkers. Avidity has selected the 2 mg/kg dosage based on favorable safety, tolerability, and efficacy data from previous studies. This dosage aims to maintain continuous suppression of DUX4, crucial for mitigating muscle toxicity.

Initial data from June demonstrated promising results, with del-brax showing unprecedented reductions in DUX4-regulated genes, significant decreases in novel circulating biomarkers and creatine kinase, and trends of functional improvement. These findings were presented at the 31st Annual FSHD Society International Research Congress.

The FORTITUDE trial is a randomized, placebo-controlled, double-blind Phase 1/2 clinical trial involving around 100 participants with FSHD. It aims to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of del-brax administered intravenously. Key biomarkers, including DUX4-regulated muscle and circulating biomarkers, along with MRI measures of muscle volume and composition, will assess the therapy's activity. Although the trial is not statistically powered to determine functional benefits, it will explore clinical activity through measures of mobility, muscle strength, and patient-reported outcomes.

Participants completing the FORTITUDE trial have the option to enroll in FORTITUDE-OLE, an open-label extension study designed to evaluate the long-term safety and tolerability of del-brax. This study will continue to monitor the same parameters as the initial trial and offers participants the opportunity to receive del-brax for approximately 24 months, with the potential for extended treatment.

Del-brax comprises a proprietary monoclonal antibody targeting the transferrin receptor 1 (TfR1), conjugated with siRNA targeting DUX4 mRNA. This therapeutic approach aims to reduce the expression of DUX4 mRNA and protein in muscle cells, addressing the underlying cause of FSHD. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted Orphan designation for del-brax, with the FDA also providing Fast Track designation.

FSHD is marked by progressive muscle weakness, starting with muscles in the face, shoulders, arms, and trunk, and later affecting the lower body. This condition severely limits physical abilities, often leading to dependence on wheelchairs. The aberrant expression of the DUX4 gene in skeletal muscle leads to muscle cell toxicity and progressive muscle wasting.

Avidity Biosciences is dedicated to developing RNA therapeutics through its proprietary Antibody Oligonucleotide Conjugates (AOCs™) platform. The company's mission is to improve lives by targeting diseases previously unreachable with existing RNA therapies. Avidity's pipeline includes programs for other rare muscle diseases such as myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD), as well as efforts in cardiology and immunology.