OAC Therapy Granted Breakthrough Designation for Myotonic Dystrophy Type 1


AOC 001 previously demonstrated benefit in patients in the phase 2 MARINA trial.

The FDA has granted Breakthrough Therapy Designation to Avidity Biosciences’ antibody oligonucleotide conjugate (AOC) therapy delpacibart etedesiran (del-desiran; AOC 1001) for treating myotonic dystrophy type 1.1

"We are pleased that the FDA has granted Breakthrough Therapy designation to del-desiran for myotonic dystrophy type 1, underscoring the potential of del-desiran to be an effective treatment and the urgency of bringing this treatment to people living with DM1," Sarah Boyce, president and chief executive officer, Avidity, said in a statement.1 "Initiation is underway for our global Phase 3 HARBOR™ study as we focus on rapidly advancing del-desiran for people living with DM1, who currently have no treatment options to address the underlying cause of this devastating rare muscle disease."

Delpacibart etedesiran consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a siRNA targeting DMPK mRNA and designed to address the root cause of DM1 by reducing DMPK mRNA. The FDA has also granted Orphan Drug and Fast Track designations to the therapy, and the European Medicines Agency has granted Orphan designation to it.1

Avidity plans to initiate the global pivotal phase 3 HARBOR study of del-desiranin the second quarter of 2024. The study will have a primary endpoint of video hand opening time (vHOT) and key secondary endpoints of muscle strength as measured by hand grip strength, quantitative muscle testing (QMT) total score, and activities of daily living as measured by DM1-Activ.1

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Avidity recently reported positive long-term data from the phase 2 MARINA-OLE trial (NCT05479981) demonstrating efficacy on these measures compared to natural history as of January 2024. The study included over 265 infusions of AOC 1001 totaling 61.1 patient-years of experience. All 37 participants entered the OLE where they received either 2 mg/kg doses of AOC 1001 escalating to 4 mg/kg or continued to be dosed at 4 mg/kg throughout. In the OLE, 35 patients (95%) experienced adverse events (AEs), most of which were mild or moderate. The most common related AEs reported in 2 or more participants included nausea and headache.2

There were no discontinuations from the OLE and all patients remain in the ongoing study. Several serious AEs such as nausea/vomiting, worsening of atrial fibrillation, and chest pain, were unrelated to AOC 1001 and consistent with DM1. Of note, one participant had acute cholelithiasis and biliary pancreatitis.2

In terms of efficacy, the 4 mg/kg group of AOC 1001 provided consistent and durable improvements in a number of measure of strength, including hand grip and Quantitative Muscle Testing total score. In addition, treated patients demonstrated improvements in myotonia and DM1-Activ, a patient reported outcome that measures activities of daily living.2

"The long-term data from the MARINA-OLE study demonstrating that del-desiran improved measures of disease progression in DM1 patients compared to natural history data is remarkable," study investigator John W. Day, MD, PhD, professor of neurology and pediatrics, and director, Division of Neuromuscular Medicine, Stanford University School of Medicine, said in a statement."The favorable long-term safety data and consistent, durable improvement in myotonia, muscle strength and patient-reported outcomes measures show the potential of del-desiran to make a meaningful difference in the lives of DM1 patients. I am very encouraged by the prospect of del-desiran as a potential treatment for DM1."

1. Avidity Biosciences Receives FDA Breakthrough Therapy Designation for Delpacibart Etedesiran (AOC 1001) for Treatment of Myotonic Dystrophy Type 1. News release. Avidity Biosciences. May 8, 2024. https://aviditybiosciences.investorroom.com/2024-05-08-Avidity-Biosciences-Receives-FDA-Breakthrough-Therapy-Designation-for-Delpacibart-Etedesiran-AOC-1001-for-Treatment-of-Myotonic-Dystrophy-Type-1
2. Johnson N, Day J, Hamel J, et al. Initial results of the phase 2 open-label extension study of AOC 1001 in adults with myotonic dystrophy type 1: MARINA-OLE. Presented at: MDA Clinical and Scientific Conference; March 3-6, 2024; Orlando, FL. POSTER T307
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