MDA 2025: DYNE-101 improves finger function in DM1 clinical trial
Other gains in muscle, motor function seen in ongoing Phase 1/2 study
Treatment with DYNE-101 is leading to improvements in muscle function — with notable gains in finger function — among people with myotonic dystrophy type 1 (DM1) in a Phase 1/2 clinical trial, according to updated interim data.
DM1 patients given the experimental therapy in the ongoing ACHIEVE study (NCT05481879) were able to open and close their middle finger faster after six months, while those on a placebo did so more slowly, the new data show. Other gains in motor function and muscle strength were also seen in treated patients versus those given the placebo.
Further, no serious side effects related to DYNE-101 have been reported, per the researchers.
“DYNE-101 has a favorable safety profile and results in early improvement in molecular biomarkers and clinical outcomes in DM1,” the team concluded in a study abstract.
The findings were presented at the Muscular Dystrophy Association‘s 2025 MDA Clinical & Scientific Conference, held last week in Dallas and virtually, by James Lilleker, PhD, a consultant neurologist and study investigator at the University of Manchester. Lilleker’s talk was titled “Safety and Efficacy of DYNE-101 in Adults with DM1: Phase 1/2 ACHIEVE Trial Data.” The work was funded by DYNE-101’s developer Dyne Therapeutics.
DYNE-101 aims to correct splicing activity in DM1 patients
When DNA is read to produce protein, the genetic code is copied into a temporary molecule called RNA, which is then used as a template to produce protein. DM1 is caused by mutations in the DMPK gene that result in the production of an abnormally long RNA that forms clumps in muscle cells, interfering with normal function. This extra-long RNA particularly causes issues with splicing, which is a type of RNA processing that’s key for making proteins.
DYNE-101 contains oligonucleotides — small pieces of genetic material — that are designed to bind to and neutralize the mutant DMPK RNA. The oligonucleotides are bound to antibodies that direct them specifically to muscle cells.
The therapy is now being tested in DM1 in ACHIEVE — in which a total of 56 patients, as of the MDA presentation, had been given various doses. Available data have suggested that DYNE-101 is generally well tolerated, with no reports of serious side effects to date.
The MDA presentation focused on data from participants given DYNE-101 at a dose of 6.8 mg/kg every eight weeks. This dose has been selected for further testing in ACHIEVE, which is still enrolling adults with DM1, ages 18 to 49, at sites in Europe and New Zealand.
At this dose, patients experienced correction in a measurement of splicing activity, by an average of 25% on a standard splicing index.
DM1 is characterized by myotonia, a symptom marked by muscles that are unable to relax. As a result, people with DM1 tend to have a reduced ability to open and close their hands at speed. Video-based tests showed that patients given the 6.8 mg/kg dose of DYNE-101 could open and close their middle finger more quickly, by nearly three seconds, after six months. By comparison, the same measure was slowed by about half a second in patients given the placebo in the ACHIEVE study.
This reflects “quite a big decrease in myotonia in the treated group,” Lilleker said.
Patients given DYNE-101 also moved faster on tests of their ability to walk or run 10 meters (about 33 feet) and to go from sitting to standing five times in a row. Scores related to quantitative muscle testing, a measure of muscle strength, and patient-reported measures of overall health status also improved following DYNE-101 treatment.
By contrast, all of these scores tended to get worse over time in patients given the placebo.
[These data reflect] quite a big decrease in myotonia [when muscles can’t relax, resulting in stiffness] in the treated group.
The researchers noted that the data showed strong correlations between splicing index scores at three months and motor function measures at six months. In other words, patients with better splicing correction early on tend to have better improvements in motor function later on, per the team.
This supports the idea that DYNE-101 is “treating the cause of the disease [by] correcting splicing,” Lilleker said. He cautioned, however, that all of these data come from just a small number of patients, so additional study is needed.
Patients given lower doses of DYNE-101 also showed improvements in splicing and motor function measures, as has been reported previously. These patients had the option to continue into an open-label extension study in which all are being treated with DYNE-101 at the 6.8 mg/kg dose.
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