Dyne Therapeutics has reported sustained one-year clinical improvements with its investigational therapy zeleciment basivarsen (z-basivarsen) in patients with myotonic dystrophy type 1 (DM1), demonstrating clinically meaningful functional gains at the selected registrational dose of 6.8 mg/kg administered every eight weeks. The data, presented at the 30th Annual International Congress of the World Muscle Society in Vienna, represent additional analyses from six adults with DM1 enrolled in the Phase 1/2 ACHIEVE trial.
Comprehensive Functional Improvements Across Multiple Domains
The one-year data revealed robust and sustained improvements across diverse clinical measures. Patients demonstrated meaningful gains in hand myotonia as measured by video hand opening time (vHOT), along with sustained improvements in functional endpoints including the 10-Meter Walk/Run Test (10MWR) and the 5 Times Sit to Stand Test (5xSTS).
New data presented at the congress showed improvement in the 9-Hole Peg Test (9HPT), a measure of upper limb function focused on manual dexterity and coordination. This finding extends the demonstrated benefits to fine motor skills, complementing previously reported improvements in gross motor function.
Muscle Strength Gains Span Upper and Lower Extremities
Quantitative Muscle Testing (QMT) revealed meaningful and sustained improvement from baseline in muscle strength, with new data showing improvements across all tested muscle groups in both upper and lower extremities. Specific improvements were documented in hand grip strength, elbow flexion, elbow extension, ankle dorsiflexion, knee flexion, and knee extension.
"This week we are presenting additional analyses from the data cut shared in June showing that the improvements in function and strength span both the upper and lower limbs, and are clearly meaningful to both patients and physicians," said Doug Kerr, M.D., Ph.D., chief medical officer of Dyne Therapeutics.
Patient-Reported Outcomes Support Clinical Meaningfulness
The Myotonic Dystrophy Health Index (MDHI) patient-reported outcome measure showed meaningful and sustained improvement from baseline, including in six subscales assessing central nervous system disease manifestations such as cognitive impairment, sleep disturbances, fatigue, communication, emotional issues and pain.
Additional new data demonstrated improvements in other MDHI subscales including mobility, ability to perform activities, and upper extremity function. These patient-reported improvements support the clinical meaningfulness of the objective improvements observed in QMT, 10MWR, 5xSTS, and 9-HPT assessments.
Global Impression Scales Confirm Meaningful Benefits
Both Patient Global Impression of Change (PGI-C) and Clinician Global Impression of Change (CGI-C) scales showed improvements from baseline in overall disease burden, providing convergent evidence of meaningful therapeutic benefit from both patient and physician perspectives.
"I believe the data for z-basivarsen support its potential to bring a wide range of benefits to DM1 patients, helping to improve their ability to function and carry out their daily lives in a way that will really matter to them," said Valeria Sansone, M.D., Ph.D., Clinical and Scientific Director at the Clinical Center NeMO in Milan and principal investigator in the ACHIEVE trial.
Favorable Safety Profile Maintained
Safety and tolerability data from 56 patients enrolled through the 6.8 mg/kg every eight weeks cohort of the ACHIEVE trial continued to demonstrate a favorable safety profile, with no related serious treatment emergent adverse events identified.
Mechanism and Regulatory Status
Z-basivarsen consists 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. The therapy is designed to reduce toxic nuclear DMPK RNA to release splicing proteins and allow normal mRNA processing, addressing the underlying spliceopathy that drives DM1's multi-system manifestations.
The investigational therapy has received Breakthrough Therapy, Orphan Drug and Fast Track designations from the U.S. Food and Drug Administration, along with Orphan Drug designation from the European Medicines Agency for DM1 treatment.
Disease Context and Unmet Need
Myotonic dystrophy type 1 affects approximately 40,000 people in the U.S. and 55,000 people in the EU. The rare, progressive, genetic neuromuscular disease causes widespread symptoms including muscle weakness, myotonia, cardiac arrhythmias, respiratory issues, gastrointestinal dysfunction, cognitive impairments, excessive daytime sleepiness, fatigue and dysregulated sleep. Despite well-understood genetic causes, no approved disease-modifying treatments currently exist for DM1.
The ACHIEVE trial is a global, randomized, placebo-controlled, double-blind Phase 1/2 study that has initiated a registrational expansion cohort to support potential regulatory submissions, including Accelerated Approval in the U.S., with video hand opening time as the primary endpoint at six months compared to placebo.
