Designed to treat the underlying cause of FSHD, AOC 1020 will be evaluated on safety, tolerability, pharmacokinetics, and pharmacodynamics in a cohort of 68 adults with the disease.
Sarah Boyce
After the FDA recently cleared the company’s investigational new drug (IND) application, Avidity Biosciences announced the phase 1/2 trial of AOC 1020, an RNA therapeutic, for the treatment of adults with facioscapulohumeral muscular dystrophy (FSHD).
FSHD, an autosomal dominant disease caused by the abnormal expression of DUX4, affects approximately 16,000 to 38,000 people in the United States alone. Named FORTITUDE, the randomized, placebo-controlled, double-blind trial will include 68 patients with FSHD to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenous administration of AOC 1020. In addition to the double-blind treatment period, eligible patients who complete the trial will have the option to enter in an open-label extension.
"Advancing AOC 1020 into the phase 1/2 FORTITUDE study is a significant milestone for the FSHD community and our proprietary AOC platform. People living with FSHD have no approved treatments and experience life-long, progressive loss of muscle function leading to fatigue and disability," Sarah Boyce, president and chief executive officer, Avidity, said in a statement.1 "AOC 1020, our second siRNA AOC, is designed to directly target the disease-causing gene, DUX4, with the goal of treating the underlying biological cause of FSHD. We now have three clinical programs in development for 3 distinct rare diseases that have no approved therapies."
AOC 1020, designed to treat the underlying cause of FSHD, consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 conjugated with a siRNA targeting DUX4 mRNA. Despite not being statistically powered to assess functional benefit, the study will still explore the clinical activity of the agent using measures of mobility and strength, as well as patient-reported outcomes and quality of life measures. Additionally, the agent will also be assessed using key biomarkers, including MRI measures of muscle volume and composition.
"We are grateful for companies like Avidity that are working to address a significant unmet need in the FSHD community," Mark A. Stone, chief executive officer, FSHD Society, said in a statement.1 "Patients as well as their caregivers and families live with the burden of this devastating disease every day and are in desperate need of treatment options that can improve quality of life. As FSHD is a progressive disease, the impact is debilitating and often results in an inability to do everyday activities like brushing teeth or getting dressed. There is a long road ahead, but today marks an important step and gives hope to everyone in our community impacted by FSHD."
A questionnaire-based study from Saudi Arabia on sleep quality revealed that sleep-related disorders, such as obstructive sleep apnea, are relatively common in patients with Duchenne muscular dystrophy.
In addition to AOC 1020, Avidity is developing 2 other agents—AOC 1044 and AOC 1001—for the potential treatment of Duchenne muscular dystrophy and myotonic dystrophy type 1, respectively. Recently, the FDA placed a partial clinical hold on participant enrollment for the phase 1/2 MARINA trial evaluating AOC 1001; however, they noted that all current participants, whether they’re on active drug or placebo, could continue in their current dosing cohort and roll over into the MARINA open-label extension, where they will receive AOC 1001 as planned.
Medical treatments for FSHD are relatively few, and none are specific to the disease. There are no approved therapies that can halt or reverse the effects of FSHD, but there are treatments and devices to help alleviate many of the symptoms. Patients with FSHD will typically take anti-inflammatory drugs such as nonsteroidal anti-inflammatories, to improve comfort and mobility, while other antidepressants or antiepileptics are sometimes used for chronic pain.
