AOC 1020 Now on FDA’s Fast Track as FSHD Treatment

Status granted to potential therapy for facioscapulohumeral muscular dystrophy

Joana Vindeirinho, PhD avatar

by Joana Vindeirinho, PhD |

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The U.S. Food and Drug Administration (FDA) has given fast-track designation to AOC 1020, an investigational therapy for facioscapulohumeral muscular dystrophy (FSHD) developed by Avidity Biosciences.

This designation allows more frequent interactions between a company and the regulatory agency, with the goal of speeding the development and review processes of therapies that have the potential to improve serious disorders in need of new treatments.

“The FDA Fast Track designation for AOC 1020 reinforces the importance of finding an effective treatment to help people living with FSHD, a devastating and debilitating muscular dystrophy disorder with no treatment options,” Steve Hughes, MD, chief medical officer of Avidity, said in a press release.

Avidity is currently running a Phase 1/2 clinical trial (named FORTITUDE) to assess the safety and clinical activity of AOC 1020 in adults with FSHD. The company plans to present preliminary findings from the trial in the first half of 2024.

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FSHD is a form of muscular dystrophy caused by abnormal expression (activity) of the gene DUX4, which is responsible for the production of the DUX4 protein. This protein is important for embryonic development, but its production is blocked in most tissues in the adult body.

In people with FSHD, DUX4 expression is not blocked, leading to the production of DUX4 in cells and tissues where it should not be present. This abnormal production of DUX4 is considered toxic to muscle cells, leading to the progressive muscle weakening characteristic of FSHD.

AOC 1020 was designed to treat this abnormal expression of DUX4, and it belongs to a new type of RNA therapeutics, named antibody oligonucleotide conjugates, developed by Avidity.

The therapy consists of an antibody attached to a type of short RNA molecule, called “short interfering RNA,” or siRNA, that can target messenger RNA (mRNA) for degradation. The antibody helps the siRNA enter muscles cells, where it can then bind specifically to mRNA carrying instructions for DUX4 production. The aim is to degrade DUX4 mRNA and consequently reduce the levels of DUX4 protein in muscle cells.

The effect of AOC 1020 was tested in mice, in which one intravenous (into-the-vein) dose of the therapy was able to prevent muscle weakness, according to Avidity. The effect was assessed by three different functional assays:  treadmill running, in vivo force test, and compound muscle action potential (electrical stimulation of muscle fibers).

FORTITUDE clinical trial

The FDA cleared Avidity’s investigational new drug application for AOC 1020 in September 2022, clearing the way for the Phase 1/2 FORTITUDE trial. For this randomized trial, Avidity plans to enroll about 70 adult participants with FSHD to test AOC 1020, delivered intravenously, against a placebo.

The main objective of the trial is to assess the safety and tolerability of the therapy, with other goals including the evaluation of its pharmacokinetics (the movement of a medication into, through, and out of the body) and pharmacodynamics (the effects of the medication on the body).

Although FORTITUDE is not statistically designed to assess functional benefit, the trial will still evaluate patient-reported outcomes and quality of life, as well as mobility and muscle strength measures. At the end of the treatment period, FORTITUDE participants will have the option to enroll in a planned open-label extension study.

“We look forward to working collaboratively with the FDA to bring the first RNA therapy directly targeting DUX4 to patients as quickly as possible,” Hughes said.

Avidity currently has two other RNA therapy candidates for muscular dystrophy in Phase 1/2 trial development: AOC 1001, designed for the treatment of myotonic dystrophy type 1, and AOC 1044, designed for the treatment of people with Duchenne muscular dystrophy with mutations amenable to exon 44 skipping. The trial for AOC 1044 (NCT05670730) is recruiting. More information is available here.