Promising Outcomes in Multiple Endpoints Reported with Delpacibart Etedesiran Treatment for Myotonic Dystrophy Type 1

Analysis of long-term data from the MARINA-OLE clinical trial (NCT05479981) demonstrated reversal of disease progression in individuals with myotonic dystrophy type 1 (DM1) who were treated with delpacibart etedesiran (del-desiran/AOC 1001; Avidity Biosciences, San Diego, CA). These results were presented at the 2024 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference.

The open-label, multi-center phase 2 trial includes 37 participants with DM1 who were previously enrolled in the Phase 1/2 MARINA clinical trial (NCT05027269). MARINA-OLE participants received quarterly doses of 4 mg/kg delpacibart etedesiran regardless of their previously assigned active or placebo treatment. Delpacibart etedesiran, an antibody oligonucleotide conjugate designed to reduce levels of disease-related DMPK mRNA, has been granted orphan designation by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) and fast track designation by the FDA.

Compared with data reported from END-DM1, a natural history study to establish biomarkers and clinical endpoints in DM1, results of the MARINA-OLE study showed consistent and durable improvements across the following endpoints associated with delpacibart etedesiran treatment:

• Myotonia (video hand opening time)
• Multiple measures of strength, including hand grip, quantitative muscle testing (QMT) total score, elbow extension and flexion, knee extension and flexion, and ankle dorsiflexion
• DM1-Activ, a patient reported outcome (PRO) that measures activities of daily living (eg, taking a shower, visiting family or friends, and walking up stairs)

Delpacibart etedesiran exhibited favorable safety and tolerability profiles; all related adverse events were mild or moderate. The most common adverse events reported in 2 or more participants were nausea and headache. Avidity Biosciences has accelerated a global phase 3 HARBOR trial which will begin in the second quarter of 2024. 

"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," said John W. Day, MD, PhD, study author and Director, Division of Neuromuscular Medicine at Stanford University School of Medicine.