Investigational Drug Shows Promise In Myotonic Dystrophy Type 1

TL;DR

Prime Big Deal Days · Oct 6–7Offer from Amazon

Get comfort and care essentials delivered free — and shop member deals

• Fast, free delivery on millions of items
• Access to Prime Big Deal Days deals on October 6–7
• Prime Video, Amazon Music and more included

Start your free Prime trial →Free trial for eligible customers · Cancel anytime

As an affiliate, we earn on qualifying purchases.Hide

A phase I/II ACHIEVE trial analysis found that 26 people with myotonic dystrophy type 1 had sustained improvements across several measures after treatment with investigational z-basivarsen. The results are preliminary; a larger registrational cohort is expected to report topline results in the first quarter of 2027.

An analysis of 26 participants in the phase I/II ACHIEVE trial found sustained improvements in hand myotonia, physical function and muscle strength after treatment with investigational z-basivarsen, according to results presented October 3 at a neuromuscular medicine meeting. The findings offer an early signal for a drug being developed for myotonic dystrophy type 1 (DM1), but the analysis is not a definitive test of efficacy and does not establish that the treatment is safe or effective for general use.

The pooled-dose analysis included participants in ACHIEVE’s multiple ascending dose portion and followed them for up to 12 months. Most received doses below the selected registrational dose of 6.8 milligrams per kilogram every eight weeks. The analysis was designed to examine whether the improvement pattern previously observed in a smaller group of six participants treated at that dose also appeared in a larger group.

At six months, the pooled group’s average video hand-opening time (vHOT) had fallen by 3.2 seconds from a mean baseline of 8.2 seconds. The placebo group in the multiple ascending dose portion had an average vHOT increase of 0.4 seconds over the same period; the reported difference in change was 3.6 seconds in favor of the pooled-dose group. The presentation described improvements from baseline in the pooled group’s 5-times sit-to-stand test and quantitative muscle testing scores through one year, as well as improvement in patient-reported disease burden. The source report did not provide numerical effect sizes for those other measures.

Shauna Andersson, MD, PhD, Dyne Therapeutics’ vice president of clinical development, presented the findings. She said the group showed a similar pattern to the earlier six-person cohort and that comparisons with an untreated natural-history cohort showed divergence across reported endpoints at 12 months. The company also reported a favorable safety profile in the analysis. Listed treatment-related adverse events included infusion-related reactions, nasopharyngitis, diarrhea, headache, procedural pain, influenza and back pain; no serious treatment-emergent adverse events related to the study drug were identified.

A Potential Treatment Beyond Symptom Management

DM1 is a progressive genetic disorder that can affect muscle function and other parts of the body. There are currently no disease-modifying therapies available for the condition, and care is focused on managing symptoms. A treatment that improves measurable function could address an important unmet need, particularly if benefits are confirmed in larger, controlled studies.

The reported measures are relevant to everyday movement: vHOT assesses how quickly a person can open the hand after making a fist, while the 5-times sit-to-stand test measures the time needed to rise from a chair repeatedly. However, improvements on trial measures do not by themselves show how much patients’ daily lives change or how durable any benefit will be beyond the study period. The current findings are a promising early signal, not proof of clinical benefit or a basis for treatment outside a trial.

How ACHIEVE Fits the Drug’s Development

Z-basivarsen, also known as DYNE-101, is an investigational antisense oligonucleotide linked to an antibody fragment that binds to transferrin receptor 1. It is designed to reduce toxic DMPK RNA in cell nuclei, with the aim of allowing proteins involved in RNA splicing to function and supporting more normal messenger RNA processing. This proposed mechanism is being tested; the reported clinical findings do not, on their own, confirm how the drug works in patients.

The drug is under study in the phase I/II ACHIEVE trial and the phase III HARMONIA trial, which the source report said was recruiting. ACHIEVE also includes a registrational expansion cohort intended to support potential regulatory submissions, including a possible accelerated approval application in the United States. Its primary endpoint is change from baseline in middle-finger myotonia measured by vHOT at six months versus placebo. The 71 participants enrolled in that cohort had a mean baseline vHOT of 8.3 seconds.

Questions Before Efficacy Is Established

The pooled-dose results are from a small group in an early-stage trial, and participants received different doses. The reported six-month vHOT comparison included a placebo group, while the 12-month comparison highlighted by the presenter was against an untreated natural-history cohort. Such comparisons can provide context but may not establish the same level of evidence as a randomized, controlled comparison within a trial. The source report does not give detailed numerical results for the 12-month functional and strength measures or explain all limitations of the analysis.

Longer-term effects, the size and clinical importance of improvements, and the safety profile in a larger population remain uncertain. The report also does not provide enough detail to determine how the findings vary across different patient characteristics or dose levels. Z-basivarsen remains investigational; no regulatory approval or availability for routine DM1 treatment was reported.

Registrational Results Expected in 2027

The next reported milestone is topline data from ACHIEVE’s 71-person registrational expansion cohort, planned for the first quarter of 2027. That cohort will assess the change in middle-finger myotonia at six months against placebo, addressing a different and more direct comparison than the natural-history analysis described in the current report.

The phase III HARMONIA trial is also recruiting, according to the source material, with change from baseline in the 5-times sit-to-stand test at 12 months as its primary endpoint. Those results will be needed, alongside further safety data, to clarify whether the improvements seen in ACHIEVE are reproducible and sufficient to support a regulatory application. No HARMONIA results or approval decision were available in the report.

Key Questions

What is z-basivarsen?

Z-basivarsen, also called DYNE-101, is an investigational antisense drug being studied for DM1. It is designed to reduce toxic DMPK RNA and support more normal RNA processing. Its proposed effects remain under clinical investigation.

What did the ACHIEVE analysis find?

In a pooled group of 26 participants, researchers reported sustained improvements from baseline in hand myotonia, sit-to-stand function and muscle strength. At six months, average vHOT improved by 3.2 seconds from an 8.2-second baseline; the placebo group’s average vHOT worsened by 0.4 seconds.

Is z-basivarsen approved for DM1?

No approval was reported. Z-basivarsen is investigational, and the findings described are not enough to establish that it is effective or appropriate for routine treatment.

When are the next results expected?

Topline results from ACHIEVE’s registrational expansion cohort are planned for the first quarter of 2027. The phase III HARMONIA trial is also recruiting, but the report did not give a date for its results.

Source: rss