Avidity Biosciences has initiated enrollment for a new patient cohort in its Phase 1/2 FORTITUDE clinical trial, evaluating delpacibart braxlosiran (del-brax) as a potential disease-modifying therapy for facioscapulohumeral muscular dystrophy (FSHD). This cohort aims to assess the effects of del-brax on key disease biomarkers, with the goal of securing accelerated approval from the FDA.
Targeting the Root Cause of FSHD
According to Avidity, del-brax is the first potential treatment to directly target the underlying cause of FSHD. FSHD is characterized by a genetic mutation leading to the aberrant production of the DUX4 protein in cells, which is believed to be toxic and drive disease symptoms. Del-brax, previously known as AOC 1020, is designed to reduce DUX4 protein production by targeting its messenger RNA (mRNA). The therapy utilizes an antibody that binds to the transferrin receptor 1 in muscle cells, along with a small interfering RNA (siRNA) to reduce DUX4 mRNA levels.
FORTITUDE Trial Details
The FORTITUDE trial (NCT05747924) is enrolling patients aged 16 to 70 at sites across the U.S., U.K., and Canada. The biomarker cohort will evaluate the impact of del-brax on DUX4-regulated biomarkers. The primary goals include assessing changes in circulating DUX4 protein levels and the activity of DUX4-regulated genes. Participants in the biomarker cohort will receive del-brax via intravenous infusion at a dose of 2 mg/kg every six weeks.
Promising Early Results
Early findings from the FORTITUDE trial, presented by Avidity, demonstrated that three doses of del-brax at 2 mg/kg led to reductions in DUX4-regulated gene activity compared to placebo. These early results also indicated trends toward improved muscle function after four months of treatment, with no significant safety concerns reported.
Accelerated Approval Pathway
The FDA's accelerated approval pathway allows conditional approval of therapies based on early biological data suggesting potential patient benefit. Avidity plans to use the data from the biomarker cohort to support an application for accelerated approval of del-brax. To maintain accelerated approval, Avidity would be required to conduct further studies to confirm the clinical benefits of the treatment.
Regulatory Designations and Future Studies
The FDA has granted del-brax both fast track and orphan drug designations, which are designed to expedite the development and review of promising new therapies for rare diseases. Patients completing the main FORTITUDE trial are being invited to enroll in the Phase 2 FORTITUDE-OLE trial (NCT06547216), an open-label extension study assessing the long-term safety, tolerability, and efficacy of del-brax over approximately two years of treatment. The FORTITUDE trial is expected to conclude in April 2027.
"We are advancing our clinical studies for del-brax as quickly as possible as we understand the urgency to bring a potential new treatment to people living with FSHD who have no treatment options," said Steve Hughes, MD, Avidity’s chief medical officer.
