Avidity’s Del-desiran Shows Promise for Myotonic Dystrophy Type 1, Phase 3 Trial Underway

A new investigational therapy, del-desiran (also known as AOC 1001), is showing promise for the treatment of myotonic dystrophy type 1 (DM1), a progressive and often fatal neuromuscular disease. Final results from the Phase 1/2 MARINA® trial were published in the February 19 issue of The New England Journal of Medicine, demonstrating a reduction in key biomarkers and improvements in functional measures. A Phase 3 trial, HARBOR™, is currently underway and has completed enrollment.

Understanding Myotonic Dystrophy Type 1

Myotonic dystrophy type 1 (DM1) affects an estimated 80,000 people in the United States and Europe. The disease is caused by an expansion of CUG repeats in the DMPK gene, leading to the accumulation of toxic mRNA and subsequent disruption of RNA processing . This disruption impacts skeletal, cardiac, and smooth muscle, as well as other systems, resulting in symptoms like myotonia, muscle weakness, respiratory problems, and cognitive impairment .

How Del-desiran Works

Del-desiran is an Antibody Oligonucleotide Conjugate (AOC) developed by Avidity Biosciences. It’s designed to address the root cause of DM1 by reducing levels of the disease-related mRNA, DMPK. The therapy consists of a monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a little interfering RNA (siRNA) that targets DMPK mRNA , , .

Key Findings from the Phase 1/2 MARINA® Trial

The Phase 1/2 MARINA trial, a randomized, double-blind, placebo-controlled study, evaluated the safety and tolerability of del-desiran in adults with DM1. Results published in the New England Journal of Medicine showed:

• Effective delivery of del-desiran (siRNA) to muscle, with a mean approximately 40% reduction in DMPK mRNA across all treated participants .
• Improvements in splicing of muscle-specific genes with del-desiran doses of 2 mg/kg and 4 mg/kg .
• Improvements in exploratory functional measures, including hand function/myotonia, muscle strength, mobility, and patient-reported outcomes .
• Acceptable safety and tolerability, with most adverse events being mild or moderate .

Two serious adverse events occurred, one of which was deemed drug-related, in participants receiving higher doses of del-desiran .

Phase 3 HARBOR™ Trial Underway

Del-desiran is currently being evaluated in the global Phase 3 HARBOR™ trial, which enrolled approximately 150 people with DM1 aged 16 and older . The primary endpoint is video hand opening time (vHOT), a measure of myotonia. Key secondary endpoints include muscle strength and activities of daily living. The trial completed enrollment in July 2025, and topline data are expected in the second half of 2026 .

Participants in the HARBOR trial have the option to enroll in an open-label extension trial, HARBOR-OLE™ .

Future Outlook

Avidity Biosciences is focused on advancing del-desiran as a potential first-in-class therapy for DM1. The ongoing Phase 3 HARBOR study and the positive data from the Phase 1/2 MARINA trial offer hope for individuals and families affected by this debilitating disease.