Learn more about our positive initial FORTITUDE™️ data including unprecedented reductions in DUX4 related genes and trends of functional improvement in people living with FSHD
We are advancing and expanding our innovative AOC pipeline to offer treatment options for patients and their families across a wide range of therapeutic areas. We have three AOC programs for three distinct rare diseases in clinical development from our muscle disease franchise: myotonic dystrophy type 1 (DM1), facioscapulohumeral muscular dystrophy (FSHD), and Duchenne Muscular Dystrophy (DMD). Our pipeline also includes advancing AOCs to address additional DMD, rare skeletal muscle, and rare precision cardiology programs. We continue to broaden our reach of AOCs in other indications including cardiology and immunology through partnerships.
Facioscapulohumeral Muscular Dystrophy
Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive, and variable hereditary muscle-weakening condition marked by life-long, relentless loss of muscle function, significant pain, fatigue, and progressive disability. It is one of the most common forms of muscular dystrophy, with onset typically in teens and young adults. FSHD affects approximately 16,000 to 38,000 people in the U.S. alone. Currently, there are no approved treatments for people living with FSHD. Current treatment approaches are focused on support for activities of daily living and mobility, improved functioning and lowering the risk of complications. They include physical therapy, exercise, pain management and orthopedic interventions.
FSHD is characterized by progressive and often asymmetric skeletal muscle loss that initially causes weakness 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 caused by the abberant expression of the DUX4 (double homeobox 4) gene in the skeletal muscle, which activates genes that are toxic to muscle cells and leads to a series of downstream events that result in skeletal muscle wasting and compromised muscle function. Skeletal muscle weakness results in physical limitations throughout the whole body 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.
FSHD Disease Process:
Delpacibart braxlosiran or del-brax (AOC 1020)
We are developing and have designed delpacibart braxlosiran or del-brax (AOC 1020) to treat the underlying cause of facioscapulohumeral muscular dystrophy (FSHD), which is caused by the abnormal expression of the DUX4 gene. Del-brax aims to reduce the expression of DUX4 mRNA and DUX4 protein in muscles in people living with FSHD. Del-brax consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a siRNA targeting DUX4 mRNA. Del-brax is currently in Phase 1/2 development as part of the FORTITUDE™ trial in adults with FSHD and is the first potential therapy to directly target DUX4 in people living with FSHD. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) granted Orphan designation for del-brax and the FDA has granted del-brax Fast Track designation.
Initiation of the Biomarker Cohort in Phase 1/2 FORTITUDE™ Trial for Del-brax
In October 2024, we announced the initiation of the biomarker cohort in the Phase 1/2 FORTITUDE™ trial of del-brax. The biomarker cohort in the FORTITUDE trial will assess the impact of del-brax 2 mg/kg every six weeks in people living with FSHD, ages 16-70. The primary endpoints of the study are changes in DUX4 regulated gene expression and DUX4 regulated circulating biomarker. We are pursuing a potential accelerated approval strategy path for del-brax and expect enrollment in the biomarker cohort to be completed in the first half of 2025. We remain on track to initiate the functional cohort for del-brax in the first of half of 2025.
Preliminary Data Presented at 2024 FSHD Society International Research Congress
In June 2024, Avidity announced unprecedented data from the Phase 1/2 FORTITUDE™ trial in people living with FSHD. Del-brax data demonstrate unprecedented and consistent reductions of greater than 50% in DUX4 regulated genes, trends of functional improvement, and favorable safety and tolerability in people living with facioscapulohumeral muscular dystrophy (FSHD). Avidity plans to accelerate initiation of registrational cohorts in the FORTITUDE study. The initial assessment from the randomized, double-blind, placebo-controlled Phase 1/2 FORTITUDE trial of del-brax provides a four-month look at the safety and tolerability for all 39 participants across two dose levels (2 mg/kg and 4 mg/kg). For the four-month assessment in the 2 mg/kg cohort, participants received a single-dose of 1 mg/kg del-brax followed by two doses of 2 mg/kg del-brax (siRNA dose), or placebo. Del-brax is the first investigational therapy designed to treat the underlying cause of FSHD, which is caused by the abnormal expression of a gene called double homeobox 4 or DUX4. FSHD is a rare, hereditary disorder marked by life-long, relentless loss of muscle function, significant pain, fatigue, and progressive disability. Currently, there are no approved therapies for the treatment of FSHD.
The Phase 1/2 FORTITUDE™ trial is a randomized, placebo-controlled, double-blind clinical trial designed to evaluate single and multiple doses of delpacibart braxlosiran or del-brax (AOC 1020) in approximately 100 participants with facioscapulohumeral muscular dystrophy (FSHD). The study is ongoing with dose escalation cohorts A and B fully enrolled and the biomarker cohort currently enrolling participants. The FORTITUDE study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of del-brax administered intravenously. Activity of del-brax will be assessed using key biomarkers, including DUX4-regulated muscle and circulating biomarkers and 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 del-brax 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 FORTITUDE-OLE, an open-label extension study once participation in the FORTITUDE study is complete. For more information about the FORTITUDE trial, visit the FORTITUDE study website or visit http://www.clinicaltrials.gov and search for NCT05747924.
The Phase 2 FORTITUDE-OLE™ is an open-label, multi-center trial designed to evaluate the long-term safety and tolerability of delpacibart braxlosiran or del-brax (AOC 1020) in participants with facioscapulohumeral muscular dystrophy (FSHD) who were previously enrolled in the FORTITUDE Phase 1/2 trial. This trial will continue to evaluate the safety, tolerability, PK, PD, and efficacy of del-brax in participants that enrolled in the randomized, placebo-controlled, Phase 1/2 FORTITUDE clinical trial. Participants who enroll in the FORTITUDE-OLE study will receive del-brax regardless of whether they received active treatment or placebo in the FORTITUDE study. The total duration of active treatment with del-brax in the FORTITUDE-OLE is approximately 24 months. Avidity may extend active treatment beyond 24 months at a future timepoint. For more information on the FORTITUDE-OLE study click here or visit http://www.clinicaltrials.gov and search for NCT06547216.
