RARE Daily

Avidity Reports Positive Initial Results in FSHD Study

June 12, 2024

Rare Daily Staff

Avidity Biosciences reported positive initial phase 1/2 data from its experimental antisense oligonucleotide conjugate AOC 1020 to treat the rare muscle disease facioscapulohumeral muscular dystrophy.

Avidity said the results demonstrated “unprecedented and consistent” reductions of greater than 50 percent in DUX4 regulated genes that drive the condition, trends of functional improvement, and favorable safety and tolerability in people living with facioscapulohumeral muscular dystrophy (FSHD).

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 an open-label extension study at the end of the treatment period in the FORTITUDE study.

Avidity said it plans to accelerate initiation of registrational cohorts in the FORTITUDE study. Avidity also announced delpacibart braxlosiran as the approved international nonproprietary name of AOC 1020, abbreviated as del-brax.

Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive, and variable hereditary muscle-weakening condition marked by significant pain, fatigue, and disability. It 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 disease caused by the aberrant expression of the DUX4 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. Currently, there are no approved treatments for people living with FSHD.

AOC 1020 (del-brax) is designed to treat the underlying cause of FSHD, which is caused by the abnormal expression of a gene called double homeobox 4 or DUX4. The abnormal expression of DUX4 protein leads to changes in gene expression in muscle cells that are associated with the life-long, progressive loss of muscle function in patients with FSHD.

Del-brax aims to reduce the expression of DUX4 mRNA and DUX4 protein in muscles in people 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. In preclinical studies, a single intravenous dose with the murine version of del-brax prevented development of muscle weakness demonstrated by three functional assays – treadmill running, in vivo force and compound muscle action potential.

The U.S. Food and Drug Administration and the European Medicines Agency have granted Orphan designation for del-brax and the FDA has granted del-brax Fast Track designation.

“With the unprecedented del-brax data from the FORTITUDE trial, we are now focused on accelerating our registrational plans as we understand the urgency to develop a treatment for people living with FSHD who have no treatment options,” said Sarah Boyce, president and CEO at Avidity. “By directly targeting the root cause of FSHD, we believe that del-brax has the potential to be a first-in-class, best-in-class therapy for people living with FSHD.”

Photo: Sarah Boyce, president and CEO at Avidity

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