Laurie Gutmann, MD, professor of neurology at Indiana University, discusses data showing functional improvements with zeleciment basivarsen (z-basivarsen; DYNE-101) in patients with myotonic dystrophy type 1.
Understanding Myotonic Dystrophy Type 1
Myotonic dystrophy type 1 (DM1), also known as Steinert disease, is a rare, inherited type of muscular dystrophy. Its estimated worldwide prevalence is approximately 1 in 20,000 people. DM1 impacts the muscles and other body systems, including the heart, eyes, endocrine system, and central nervous system.
There are three forms of the disease: mild form, classic form, and congenital form (present at birth). The mild form typically causes the least severe symptoms, and patients generally have a normal lifespan. The classic form causes muscle weakness and wasting, myotonia, cataracts, and, in many cases, abnormal heart function. Adults with the classic form may become physically disabled and have a shortened lifespan. The congenital form is characterized by severe generalized weakness at birth, often accompanied by breathing complications that can be life-threatening.
DM1 is caused by an abnormal expansion of repeated DNA sequences in the DMPK gene.
Zeleciment basivarsen is an investigational therapy consisting of an antisense oligonucleotide (ASO) conjugated to an antigen-binding fragment (Fab) that binds to the transferrin receptor 1 (TfR1) to enable delivery to muscle and the central nervous system. It’s designed to improve function in individuals living with DM1 by reducing toxic DMPK RNA, releasing splicing proteins, and allowing normal mRNA processing.
Z-basivarsen has been granted Breakthrough Therapy, Orphan Drug, and Fast Track designations by the U.S. Food and Drug Administration (FDA).
Additional One-Year Clinical Data Show Improvements in DM1 Patients
Additional one-year efficacy data from the multiple ascending dose (MAD) portion of the phase 1/2 ACHIEVE trial (NCT05481879) were announced on September 29, 2026, and presented at the 2026 World Muscle Society Congress and the American Association of Neuromuscular & Electrodiagnostic Medicine annual meeting. ACHIEVE is a randomized, placebo-controlled, double-blind, phase 1/2 clinical trial evaluating the safety, tolerability, and efficacy of z-basivarsen in patients with DM1.
The pooled analysis included 25 to 26 participants from three dose groups: 3.4 mg/kg every four weeks, 5.4 mg/kg every eight weeks, and 6.8 mg/kg every eight weeks. Some participants initially received a placebo before switching to active treatment. Only 8 of the 26 participants received the selected 6.8/kg dose for the full 12 months.
The pooled data showed improvements in several areas, including:
Hand myotonia: At six months, video hand opening time improved by 3.2 seconds from baseline in the pooled treatment group, compared with a 0.4-second increase in the placebo group.
Physical function: At 12 months, participants improved their five-times sit-to-stand test by 1.2 seconds and their 10-meter walk/run test by 0.3 seconds relative to baseline.
Muscle strength: Quantitative muscle testing showed improvements in both the total score and hand grip, with each increasing by 4.8% relative to baseline.
Patient-reported outcomes: The Myotonic Dystrophy Health Index total score improved by 25.2% relative to baseline.
No treatment-related serious adverse events were identified.
Next Steps in Clinical Development
The ACHIEVE trial’s registrational expansion cohort is fully enrolled, with topline results expected in the first quarter of 2027. The study’s primary endpoint is the change in video hand opening time after six months of treatment. Dyne Therapeutics plans to use these results to support a potential U.S. accelerated approval submission in the third quarter of 2027.
Dyne Therapeutics is also conducting the phase 3 HARMONIA trial to further evaluate z-basivarsen. The HARMONIA trial is intended to confirm the treatment’s benefits and support a potential application for traditional FDA approval.
For more information, visit: https://www.globenewswire.com/news-release/2026/09/29/3371326/0/en/dyne-therapeutics-announces-additional-one-year-clinical-data-from-phase-1-2-achieve-trial-of-z-basivarsen-dyne-101-for-myotonic-dystrophy-type-1-dm1.html
To learn more about myotonic dystrophy type 1 and other rare neurological and neuromuscular disorders, visit: https://checkrare.com/diseases/neurology-nervous-system-diseases/