Zeleciment Basivarsen Shows Sustained Functional Improvement in Myotonic Dystrophy Type 1

Dyne Therapeutics reported new 12-month data from the Phase 1/2 ACHIEVE trial (NCT05481879) showing sustained improvements in myotonia, physical function, muscle strength and patient-reported outcomes with investigational zeleciment basivarsen (z-basivarsen, DYNE-101) in adults with myotonic dystrophy type 1 (DM1). The findings, presented at the 31st Annual International Congress of the World Muscle Society and the 2026 AANEM Annual Meeting, extend earlier efficacy signals from the study.

Sustained Improvements Across Functional Measures

The new analysis pooled 25 to 26 participants from three multiple ascending dose cohorts: 3.4 mg/kg every four weeks, 5.4 mg/kg every eight weeks and 6.8 mg/kg every eight weeks. The analysis included participants originally assigned to placebo who were re-baselined before receiving active treatment. Because the pooled group included different dose exposures, the results do not represent continuous treatment at the selected registrational dose. Only eight of 26 participants received 6.8 mg/kg throughout the full 12-month analysis.

At six months, video hand opening time (vHOT), a measure of hand myotonia, improved by 3.2 seconds from a mean baseline of 8.2 seconds. The placebo group showed a 0.4-second worsening, producing a 3.6-second relative difference. At 12 months, participants also improved on functional measures, with 5-times sit-to-stand improving by 1.2 seconds and the 10-meter walk/run improving by 0.3 seconds.

Muscle strength improved by 4.8% predicted from baseline for both the quantitative muscle testing total score and hand-grip score. The Myotonic Dystrophy Health Index total score improved by 25.2%, including gains across measures of cognitive impairment, sleep, fatigue, communication, emotional health and pain. Several measures also diverged from propensity-matched participants in the END-DM1 natural history study.

Targeting the Underlying RNA Splicing Defect

DM1 is caused by pathogenic expansion mutations in the DMPK gene that produce toxic RNA and disrupt RNA splicing across multiple tissues. The resulting spliceopathy contributes to muscle weakness, myotonia, fatigue, sleep and cognitive problems, cardiac abnormalities and respiratory and gastrointestinal complications. No approved disease-modifying treatment currently addresses the underlying cause of DM1.

Z-basivarsen combines an antisense oligonucleotide with an antigen-binding fragment that targets transferrin receptor 1 (TfR1). This approach is intended to improve delivery of the therapeutic payload to skeletal muscle and the central nervous system. Once delivered, the ASO reduces toxic nuclear DMPK RNA, helping release splicing proteins and restore more normal mRNA processing.

Safety Profile Remains Favorable

Updated safety findings from participants originally enrolled in the ACHIEVE MAD portion continued to show a favorable tolerability profile, with no treatment-related serious treatment-emergent adverse events identified in the reported analysis. Z-basivarsen has received FDA Breakthrough Therapy, Orphan Drug and Fast Track designations, alongside Orphan Drug designations from the EMA and Japan’s MHLW.

Registrational Development Moves Forward

Dyne selected 6.8 mg/kg administered every eight weeks as the registrational regimen following the ACHIEVE dose-escalation program. The fully enrolled registrational expansion cohort includes 71 participants, with a mean baseline vHOT of 8.3 seconds. Its primary endpoint is change from baseline in vHOT at six months versus placebo. Topline results are expected in the first quarter of 2027 and are intended to support a potential U.S. Accelerated Approval submission in the third quarter of 2027.

The company is also evaluating z-basivarsen in the global Phase 3 HARMONIA trial. The study is intended to provide confirmatory evidence for traditional U.S. approval and support regulatory submissions outside the United States. Its primary endpoint is change from baseline in the 5-times sit-to-stand test at 12 months.

The upcoming ACHIEVE REC readout will provide the next key test of whether the vHOT improvement observed in earlier cohorts can be reproduced in a larger, controlled registrational population.

Reference

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), Dyne Therapeutics, 29 September 2026

Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-101 in Participants with Myotonic Dystrophy Type 1 (ACHIEVE), ClinicalTrials.gov ID NCT05481879