Avidity Biosciences’ del-desiran granted orphan drug designation in Japan for myotonic dystrophy type 1

In a significant boost for rare disease therapeutics, Avidity Biosciences, Inc. announced that Japan’s Ministry of Health, Labour and Welfare (MHLW) has granted Orphan Drug designation to delpacibart etedesiran—known as del-desiran—for myotonic dystrophy type 1 (DM1). This milestone marks the first time an investigational therapy for DM1 has been awarded such a designation in Japan, signalling a strong vote of confidence in the drug’s therapeutic potential.

Japan’s Orphan Drug framework is designed to fast-track development for therapies targeting conditions affecting fewer than 50,000 people in the country. Benefits include reduced regulatory fees, priority consultations, and longer market exclusivity upon approval. Del-desiran now holds Orphan Drug status in Japan, the United States, and the European Union, having previously received Breakthrough Therapy, Orphan Drug, and Fast Track designations from the U.S. Food and Drug Administration (FDA) and Orphan Drug status from the European Medicines Agency (EMA).

The announcement underlines del-desiran’s potential to become the first globally approved disease-modifying treatment for DM1, a devastating and underdiagnosed genetic disorder with no approved therapies.

Why is del-desiran considered a breakthrough in the treatment of DM1?

Myotonic dystrophy type 1 (DM1) is a genetic disorder caused by a CTG trinucleotide repeat expansion in the DMPK gene, resulting in the production of toxic RNA that disrupts normal muscle function and other systemic processes. The disease presents with a wide range of symptoms, including myotonia, progressive muscle weakness, cardiac issues, respiratory complications, gastrointestinal dysfunction, and cognitive impairment. Severity and age of onset vary significantly, yet all forms are associated with premature mortality and a high burden of disability.

With no approved disease-modifying treatments, patients have had to rely on symptom management. Del-desiran, however, represents a first-in-class approach that directly targets the root cause of DM1 using Avidity’s Antibody Oligonucleotide Conjugates (AOCs™) platform. This platform enables precise delivery of RNA-targeting molecules to muscle cells by binding a monoclonal antibody to the transferrin receptor 1 (TfR1), combined with a siRNA designed to degrade toxic DMPK mRNA.

The result is a promising therapeutic that, according to emerging trial data, offers the possibility of reversing disease progression—an outcome not yet seen in the DM1 space.

How are clinical trials supporting del-desiran’s safety and long-term efficacy?

Avidity is currently running two major clinical programs—MARINA-OLE and HARBOR—to evaluate del-desiran’s clinical performance. The Phase 2 MARINA-OLE trial, an open-label extension of the earlier MARINA study, is showing sustained improvements across multiple clinical endpoints. These include video hand opening time (vHOT), a proxy for myotonia and hand function, as well as improvements in grip strength, quantitative muscle testing (QMT), and activities of daily living.

The Phase 3 HARBOR trial, now enrolling approximately 150 participants globally, is expected to conclude enrollment by mid-2025. This double-blind, placebo-controlled study aims to establish del-desiran’s efficacy and safety profile as the basis for regulatory submissions in Japan, the U.S., and the EU starting in 2026. Patients receive the treatment or placebo every eight weeks, with multiple measures—including vHOT and QMT—used to capture both muscle function and quality of life improvements. All participants are eligible for an open-label extension, ensuring long-term data collection regardless of treatment group assignment.

How does del-desiran reflect broader trends in RNA therapeutics for neuromuscular diseases?

The development of del-desiran underscores the growing potential of RNA-targeting therapies, particularly beyond hepatic applications. While most siRNA-based drugs to date have focused on the liver, Avidity’s AOC platform is designed to deliver these molecules directly to muscle tissue, unlocking treatment options for neuromuscular disorders like DM1.

This innovation arrives amid a broader wave of investment and interest in precision medicine, especially in the rare disease sector. The ability to design drugs that modulate or silence disease-causing genes is reshaping how the industry approaches untreatable conditions. Del-desiran’s trajectory, from early-stage trials to multinational regulatory recognition, illustrates how next-generation RNA platforms are no longer theoretical but are now producing clinically meaningful results.

Moreover, del-desiran could serve as a proof of concept for other therapies in Avidity’s pipeline, including candidates for facioscapulohumeral muscular dystrophy (FSHD) and Duchenne muscular dystrophy (DMD).

What does the stock market say about Avidity Biosciences and investor sentiment?

Avidity Biosciences, Inc. (NASDAQ: RNA) has seen notable market fluctuations in recent days. Despite receiving Orphan Drug designation in Japan for del-desiran, the stock fell by approximately 4.10% on April 7, closing at $25.48, part of a broader 15.92% decline over the past week. However, investor sentiment remains generally positive.

As of April 8, the stock traded at around $24.30, with a 52-week range spanning from $22.24 to $56.00, indicating significant volatility. The pullback is seen by some analysts as a temporary reaction amid broader market conditions rather than a reflection of the company’s fundamentals.

The analyst consensus currently stands at “Buy”, with a target price of $66.69, suggesting substantial upside potential. Notably, BMO Capital Markets initiated coverage in March with an “Outperform” rating and a price target of $72.00, reinforcing the long-term confidence in del-desiran’s commercial prospects.

Institutional investors also appear to be increasing their exposure. Vanguard Group Inc. and Geode Capital Management LLC have both expanded their positions, with Vanguard now holding more than 9.4 million shares valued at over $274 million. Such activity points to confidence in Avidity’s long-term pipeline and market strategy.

While insider selling has occurred—such as Kathleen P. Gallagher offloading shares worth over $160,000 in early April—this is often routine and not necessarily indicative of broader concerns.

Given the volatility, long-term investors may view the current dip as a buying opportunity, particularly as the HARBOR trial progresses and additional regulatory milestones are anticipated. That said, risk-aware investors should remain alert to trial outcomes, regulatory shifts, and broader biotech market conditions before making decisions.

With the Japanese government’s designation adding momentum to del-desiran’s global development, Avidity Biosciences is well-positioned to lead a new chapter in RNA-based treatment of neuromuscular diseases. As it approaches key clinical and regulatory milestones, market interest is likely to intensify, driven not only by the drug’s potential as a first-in-class therapy but also by its broader implications for RNA-targeting innovation.