RARE Daily

FDA Grants Breakthrough Therapy Designation for Avidity’s Treatment for Myotonic Dystrophy Type 1

May 8, 2024

Rare Daily Staff

The U.S. Food and Drug Administration granted Breakthrough Therapy designation to Avidity Biosciences delpacibart etedesiran for the treatment of myotonic dystrophy type 1.

Delpacibart etedesiran, abbreviated as del-desiran, is an investigational treatment designed to address the root cause of DM1, an underrecognized, progressive and often fatal neuromuscular disease with no approved therapies.

“The FDA granting Breakthrough Therapy designation to del-desiran for myotonic dystrophy type 1, underscores the potential of del-desiran to be an effective treatment and the urgency of bringing this treatment to people living with DM1,” said Sarah Boyce, president and CEO at Avidity. “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.”

The primary endpoint in the phase 3 HARBOR trial is video hand opening time (vHOT) and key secondary endpoints include muscle strength as measured by hand grip strength and quantitative muscle testing (QMT) total score, and activities of daily living as measured by DM1-Activ. Avidity recently reported positive long-term MARINA-OLE data demonstrating reversal of disease progression in adults living with DM1 across multiple endpoints including vHOT, muscle strength and DM1-Activ when compared to natural history data.

Myotonic dystrophy type 1 (DM1) is an underrecognized, progressive and often fatal disease caused by a triplet-repeat in the DMPK gene, resulting in a toxic gain of function mRNA. The disease is highly variable with respect to severity, presentation and age of onset, however all forms of DM1 are associated with high levels of disease burden and may cause premature mortality. DM1 primarily affects skeletal and cardiac muscle, however patients can suffer from a constellation of manifestations including myotonia and muscle weakness, respiratory problems, fatigue, hypersomnia, cardiac abnormalities, severe gastrointestinal complications, and cognitive and behavioral impairment. Currently, there are no approved treatments for people living with DM1.

Del-desiran (AOC 1001), Avidity’s lead product candidate utilizing its AOC platform, is designed to address the root cause of DM1 by reducing levels of a disease-related mRNA called DMPK. Del-desiran consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a siRNA targeting DMPK mRNA. In preclinical studies, del-desiran successfully delivered siRNAs to muscle cells, resulting in durable, dose-dependent reductions of DMPK RNA across a broad range of muscles including skeletal, cardiac, and smooth muscles. Del-desiran is currently in phase 1/2 development with the completed MARINA trial and the ongoing MARINA-OLE trial in adults with DM1. The FDA and European Medicines Agency have granted Orphan designation for del-desiran and the FDA has granted del-desiran Fast Track designation.

Photo: Sarah Boyce, president and CEO of Avidity Biosciences

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