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A phase I/II ACHIEVE trial analysis found that 26 people with myotonic dystrophy type 1 had sustained improvements in measures of hand myotonia, function and strength over 12 months while receiving z-basivarsen. The findings are preliminary: most participants received doses below the selected registrational dose, and the analysis does not establish that the drug is effective. A larger trial cohort is expected to report topline results in the first quarter of 2027.
An analysis of 26 people with myotonic dystrophy type 1 in the phase I/II ACHIEVE trial found sustained improvements in hand myotonia, physical function and muscle strength during up to 12 months of treatment with investigational z-basivarsen, according to results presented October 3 at an American Association of Neuromuscular and Electrodiagnostic Medicine meeting. The findings are encouraging but preliminary; the group included participants who received different doses, and the analysis does not establish whether the drug works.
The pooled-dose analysis followed participants in ACHIEVE’s multiple ascending dose portion through 12 months. It examined whether a broader group showed efficacy trends similar to those previously observed in a small cohort of six people treated with the selected registrational dose of 6.8 milligrams per kilogram every eight weeks. Most people in the larger group received lower doses, Dyne Therapeutics clinical development vice president Shauna Andersson said in comments reported by MedPage Today.
Hand myotonia was measured using video hand-opening time, or vHOT. The pooled group’s average starting time was 8.2 seconds; it fell by 3.2 seconds at six months, the report said. In comparison, the placebo group in the multiple ascending dose portion had an average 0.4-second increase over the same period. The reported difference between those changes was 3.6 seconds. The supplied results do not give a corresponding 12-month vHOT change for this pooled group.
Researchers also reported sustained improvement from baseline on the five-times sit-to-stand test, which assesses function, and on total scores from quantitative muscle testing. Participants also reported reduced disease burden. Andersson said comparisons with an untreated natural-history cohort showed better functional and strength outcomes and improvement in patient-reported Myotonic Dystrophy Health Index scores. The report does not provide effect sizes for those comparisons.
Andersson described the safety profile as favorable. Reported treatment-related adverse events included infusion-related reactions, nasopharyngitis, diarrhea, headache, procedural pain, influenza and back pain. She said investigators identified no serious treatment-emergent adverse events related to the study drug. These findings refer to the participants and follow-up covered by this analysis and do not settle the drug’s safety profile in larger or longer studies.
Potential Benefits Across DM1 Measures
DM1 can affect movement and muscle strength, and people living with the disorder currently have no approved disease-modifying therapy; care focuses on managing symptoms. Improvements reported across measures of hand myotonia, physical function and strength therefore make the ACHIEVE findings relevant to patients and clinicians looking for treatments that may address the disease’s effects.
The results are a signal for further study, not proof of benefit. This was a pooled analysis of 26 participants who received varying doses, and some comparisons used an untreated natural-history cohort rather than a concurrent randomized control group. The larger registrational expansion cohort and the phase III HARMONIA trial are intended to provide more evidence. Whether the changes are clinically meaningful and sustained across a broader population remains to be established.
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How ACHIEVE Tests the Drug
DM1 is a rare, progressive condition associated with mutations in the DMPK gene that disrupt RNA splicing. Adult-onset symptoms often begin between ages 20 and 40, according to the supplied report. Z-basivarsen, also known as DYNE-101, is an investigational antisense oligonucleotide linked to an antigen-binding fragment that binds transferrin receptor 1. It is designed to reduce toxic DMPK RNA in the cell nucleus and support more normal RNA processing. That is the drug’s proposed mechanism; the clinical findings reported so far do not prove that the mechanism produces lasting patient benefit.
The phase I/II ACHIEVE program includes a registrational expansion cohort designed to support potential regulatory submissions, including a possible accelerated approval application in the United States. Its primary measure is change from baseline in middle-finger myotonia, assessed by vHOT at six months against placebo. The 71 people enrolled in that cohort had a mean baseline vHOT of 8.3 seconds. Separately, the phase III HARMONIA trial is recruiting, with change in the five-times sit-to-stand test at 12 months as its primary endpoint.
Questions Before Efficacy Is Clear
The findings come from an early-phase trial analysis, not from the phase III study. The 26-person pooled-dose group included people who received different doses, and most received less than the selected 6.8 mg/kg registrational dose. The source does not give full 12-month numerical results for each endpoint, the size of the changes in sit-to-stand performance or strength, or detailed statistical analyses. It is also unclear from the reported information how comparable the natural-history cohort was on all relevant measures.
The results do not show whether improvements will persist with longer treatment, how benefits and risks compare across doses, or whether changes translate into meaningful day-to-day improvements for a wider range of people with DM1. The safety observations are limited to the group and period covered in this analysis. Regulatory decisions and any eventual availability of the drug remain uncertain.
Larger Trial Results Ahead
The next reported milestone is topline data from the 71-person ACHIEVE registrational expansion cohort, planned for the first quarter of 2027. Its primary endpoint is the change in middle-finger vHOT at six months compared with placebo. Those data should offer a more direct test of the selected dose against a control group, though the results and timing could change.
Meanwhile, the phase III HARMONIA trial is recruiting. Its primary endpoint is change from baseline in the five-times sit-to-stand test at 12 months. Results from that later-stage study will be needed to judge whether the improvements reported in ACHIEVE are confirmed in a larger trial and could support a treatment application.
Key Questions
What did the ACHIEVE analysis find?
Among 26 participants receiving pooled doses of z-basivarsen, researchers reported sustained improvements from baseline in hand myotonia, sit-to-stand function and muscle strength over follow-up. The analysis also reported improvements in patient-reported disease burden. It is preliminary evidence, not proof that the drug is effective.
What is z-basivarsen designed to do?
Z-basivarsen is an investigational antisense drug designed to reduce toxic RNA associated with DMPK gene mutations in DM1 and allow more normal RNA processing. Its proposed biological action has not, by itself, established clinical benefit.
Is z-basivarsen approved for DM1?
No. The supplied report describes z-basivarsen as an investigational drug. It says no disease-modifying therapies are currently available for DM1; treatment is focused on symptom management.
When will more results be available?
Topline results from the ACHIEVE registrational expansion cohort are planned for the first quarter of 2027. The phase III HARMONIA trial is also recruiting, but the supplied report does not give a date for its results.
Source: rss
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