One-year data from six adults with myotonic dystrophy type 1 (DM1) treated with zeleciment basivarsen at 6.8 mg/kg every eight weeks in Dyne’s Phase 1/2 ACHIEVE trial showed sustained improvements from baseline across measures of myotonia (video hand opening time), functional performance (10-Meter Walk/Run, 5 Times Sit to Stand, 9-Hole Peg Test), and quantitative muscle strength testing in both upper and lower extremities. Patient-reported outcomes on the Myotonic Dystrophy Health Index improved, including CNS-related subscales, and both patient and clinician global impression of change favored improvement. Across 56 patients enrolled through this dose cohort, no treatment-related serious adverse events were reported.
The company presented additional analyses from the selected registrational dose cohort at the World Muscle Society meeting, refining a dataset first disclosed in June. On the back of these data, Dyne has initiated a registrational expansion cohort with a primary endpoint at six months: change from baseline in middle finger myotonia by video hand opening time versus placebo. That design signals an Accelerated Approval strategy in the U.S., with a single, standardized physiologic measure at its core, supported by convergent functional readouts, strength assessments, and patient-reported benefit.
Strategically, Dyne is assembling a package aimed at regulatory comfort with an intermediate endpoint that is objective, reproducible, and mechanistically linked to disease biology, while tying it to real-world function and patient perception. The emphasis on both upper and lower limb performance plus CNS-relevant domains in the Health Index is calibrated to the multi-system nature of DM1 and the company’s TfR1-targeted conjugate architecture, which is intended to reach muscle and the central nervous system. It also reflects a broader shift in neuromuscular development toward composite evidence of benefit rather than single-lab biomarkers that have struggled to translate. The tension is sample size and generalizability: n=6 at the registrational dose is an early signal, not a population-level effect, and regulators will scrutinize consistency, magnitude, and durability as the expansion cohort reads out.
For sites, the operational footprint is clear. Video hand opening time requires rigorous training, standardized capture, and central reads to control variability across centers. Performance measures like 10MWR, 5xSTS, 9HPT, and QMT will drive demand for harmonized eCOA workflows and equipment calibration, favoring sites and CROs with neuromuscular expertise and robust quality systems. The trial’s every-eight-week dosing cadence may ease visit burden, but the multi-endpoint battery increases coordinator workload and necessitates tight scheduling to avoid learning effects. Vendors positioned in ePRO, eCOA, and centralized functional assessments stand to benefit as programs in DM1 converge on similar endpoint stacks. Regulators will need to decide whether a myotonia-based intermediate endpoint, supported by function and PROs, is sufficient to underwrite accelerated access in a disease with no approved disease-modifying therapies.
What’s next is whether the registrational expansion cohort reproduces these cross-domain gains with adequate power and shows six-month separation on the primary endpoint that is both statistically persuasive and operationally robust across geographies. Durability beyond a year, stability of the safety profile with chronic dosing, and clearer evidence of CNS-related benefit will be pivotal to the label scope. Watch also for the FDA’s stance on video-derived measures as surrogates, the design and feasibility of any required confirmatory trial, and CMC readiness for an antibody fragment–oligonucleotide conjugate at commercial scale. Finally, competition in DM1 targeting muscle delivery via TfR1 will keep pressure on differentiation; the sponsor that pairs clean, consistent functional gains with a straightforward regulatory path and pragmatic site execution will set the template for the category.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
