Early Data Shows Potential Benefit of Avidity's RNA Therapy in Muscular Dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is a rare genetic disorder that progressively weakens muscles, causing pain, fatigue, and disability. Currently, there are no approved treatments for this condition. Avidity Biosciences is developing a new RNA therapeutic called AOC 1020, now referred to as del-brax, which has shown promise in an early-phase clinical trial.

The phase 1/2 trial was designed to evaluate the safety and efficacy of del-brax in 39 participants with FSHD. The study's primary goal was to assess the safety and tolerability of the therapy, which was achieved successfully. No serious adverse events were reported, and none of the participants discontinued the study, indicating a favorable safety profile.

Del-brax is an innovative therapeutic classified as an "antibody oligonucleotide conjugate," aimed at targeting the abnormal expression of a gene called double homeobox 4 (DUX4). The trial revealed that del-brax led to more than a 50% mean reduction in multiple DUX4-regulated gene panels for 12 patients who received a 2 mg/kg dose over four months. Although specific data for participants receiving a 4 mg/kg dose were not disclosed, it was noted that all treated participants experienced at least a 20% reduction in DUX4-regulated genes. These participants were also included in the safety and tolerability assessment.

While the primary focus of the trial was not to measure functional benefits, initial results suggest that del-brax may improve muscle strength and function. Jeffrey Statland, M.D., a neurology professor at the University of Kansas Medical Center and a trial investigator, emphasized the significance of these findings. He noted that del-brax is the first therapy to directly target DUX4 and that its data showed consistent reductions in DUX4-regulated genes, along with trends indicating functional improvement in patients.

The primary readout date for this trial is set for September 2025, as per ClinicalTrials.gov. Avidity Biosciences plans to accelerate the initiation of registrational cohorts for del-brax, which has already received FDA orphan and fast track designations. These designations are crucial as they can expedite the development and review process, offering hope to those affected by FSHD.

Mark Stone, president and CEO of the FSHD Society, highlighted the lack of treatment options for one of the most common forms of muscular dystrophy. He expressed optimism about the initial del-brax data, stating that it provides hope for patients, their families, and caregivers who have long awaited a treatment.

The findings from this trial will be presented at the Annual FSHD Society International Research Congress in Colorado later this week. This event offers an opportunity for the scientific community to review the data and further evaluate the potential of del-brax as a groundbreaking treatment for FSHD.

In summary, Avidity Biosciences' del-brax has demonstrated a safe profile and indicated functional improvements in early-phase trials for FSHD, a debilitating genetic disorder with no current treatments. These promising results may pave the way for accelerated development and potential future treatment options for those affected by this condition.