Avidity Biosciences announced today that the Japan Ministry of Health, Labour and Welfare (MHLW) has granted Orphan Drug designation to delpacibart etedesiran (del-desiran) for the treatment of myotonic dystrophy type 1 (DM1). This marks the first time an investigational treatment for DM1 has received this designation in Japan.
Del-desiran is designed to address the root cause of DM1, a progressive and often fatal neuromuscular disease with no currently approved therapies. The drug has already received Breakthrough Therapy, Orphan Drug, and Fast Track designations from the U.S. Food and Drug Administration (FDA) and Orphan designation from the European Medicines Agency (EMA).
"This decision by MHLW further reinforces the significant potential of del-desiran to address the root cause of DM1 and the urgent need to bring an approved therapy to the many people impacted by this devastating rare disease in Japan and around the world," said Steve Hughes, M.D., chief medical officer at Avidity.
Promising Clinical Results
Data from the MARINA and MARINA-OLE studies have demonstrated favorable long-term safety and tolerability of del-desiran. More significantly, the treatment has shown reversal of disease progression and consistent, durable improvements across multiple clinical endpoints in people living with DM1.
The company has aligned with global regulators on the registrational path for del-desiran, which informed the design of the ongoing Phase 3 HARBOR study. Avidity expects to complete participant enrollment in this pivotal trial by mid-2025 and plans to submit marketing applications starting in 2026 across the U.S., European Union, and Japan.
Benefits of Orphan Drug Designation in Japan
Japan's MHLW grants Orphan Drug designation to treatments in development for diseases that affect fewer than 50,000 patients in Japan and for which there is a high unmet medical need. This designation provides several benefits, including:
- Prioritized consultation regarding clinical development
- Reduced consultation fees
- Tax incentives
- Priority review of applications
- Reduced application fees
- Extended registration validity period
The HARBOR Trial Design
The global Phase 3 HARBOR trial is a randomized, placebo-controlled, double-blind pivotal study evaluating del-desiran in approximately 150 people (age 16 and older) living with DM1. The trial is being conducted at approximately 40 sites globally, with patients receiving either del-desiran or placebo (1:1) every eight weeks.
The primary endpoint is video hand opening time (vHOT), which measures myotonia, a hallmark symptom of DM1. Key secondary endpoints include muscle strength as measured by hand grip strength and quantitative muscle testing (QMT) total score, as well as activities of daily living as measured by DM1-Activ.
Understanding Del-desiran's Mechanism
Del-desiran, Avidity's lead product candidate utilizing its Antibody Oligonucleotide Conjugates (AOCs) platform, works by reducing levels of a disease-related mRNA called DMPK. The drug consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a siRNA targeting DMPK mRNA.
Long-term data from the MARINA-OLE trial has shown reversal of disease progression in people living with DM1 across multiple endpoints, including improvements in hand function, myotonia, muscle strength, and activities of daily living when compared to natural history data.
About Myotonic Dystrophy Type 1
Myotonic dystrophy type 1 is an underrecognized, autosomal dominantly inherited, progressive disease caused by a triplet-repeat in the DMPK gene, resulting in a toxic gain of function mRNA. The disease varies in severity, presentation, and age of onset, but all forms are associated with high levels of disease burden and may cause premature mortality.
DM1 primarily affects skeletal and cardiac muscle, but patients can suffer from a wide range of symptoms including:
- Myotonia and muscle weakness
- Respiratory problems
- Fatigue and hypersomnia
- Cardiac abnormalities
- Severe gastrointestinal complications
- Cognitive and behavioral impairment
Currently, there are no approved treatments for people living with DM1, highlighting the significant unmet need that del-desiran aims to address.
Avidity's Broader Mission
Avidity Biosciences is focused on delivering a new class of RNA therapeutics called Antibody Oligonucleotide Conjugates. The company's proprietary AOCs are designed to combine the specificity of monoclonal antibodies with the precision of oligonucleotide therapies to address targets and diseases previously unreachable with existing RNA therapies.
Beyond DM1, Avidity is leading clinical development programs for two other rare neuromuscular diseases: Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). The company is also advancing precision cardiology development candidates for rare genetic cardiomyopathies.
As Avidity continues to advance del-desiran through clinical development, the Orphan Drug designation in Japan represents another important milestone in the company's efforts to deliver the first globally approved treatment for people living with DM1.
