Z-basivarsen shows sustained benefits in myotonic dystrophy type 1 trial

Data from the phase I/II ACHIEVE trial suggest that Dyne Therapeutics' investigational drug z-basivarsen (DYNE-101) provides sustained functional, motor, and strength benefits for patients with myotonic dystrophy type 1 (DM1). In a pooled-dose group of 26 patients, hand myotonia improved by 3.2 seconds at six months, representing a 3.6-second improvement over placebo. Currently, no disease-modifying therapies exist for DM1, a rare progressive genetic disorder.

Efficacy results of the ACHIEVE trial

• ▪In the ACHIEVE trial, 26 myotonic dystrophy type 1 patients treated with z-basivarsen showed a 3.2-second decrease in video hand-opening time at 6 months from an 8.2-second baseline, a 3.6-second improvement over the placebo group's 0.4-second increase.
• ▪In the ACHIEVE trial, myotonic dystrophy type 1 patients treated with z-basivarsen showed functional improvements in patient-reported Myotonic Dystrophy Health Index scores compared to an untreated natural history cohort.
• ▪Data from the phase I/II ACHIEVE trial suggested that the investigational drug z-basivarsen led to functional improvement, including sustained hand myotonia, motor, and strength benefits, in patients with myotonic dystrophy type 1.

Safety profile of z-basivarsen in the ACHIEVE trial

• ▪Treatment-related adverse events for z-basivarsen in the ACHIEVE trial included infusion-related reactions, nasopharyngitis, diarrhea, headache, procedural pain, influenza, and back pain.
• ▪In the ACHIEVE trial, z-basivarsen demonstrated a favorable safety profile with no serious treatment-emergent adverse events related to the study drug identified.

Registrational expansion cohort of the ACHIEVE trial

• ▪The primary endpoint for the ACHIEVE trial's registrational expansion cohort is the change from baseline in middle finger myotonia at six months.
• ▪Dyne Therapeutics plans to release topline data from the registrational expansion cohort of the ACHIEVE trial, which has enrolled 71 participants, in the first quarter of 2027.

Characteristics of myotonic dystrophy type 1

• ▪Myotonic dystrophy type 1 is a rare progressive disorder caused by mutations in the DMPK gene that disrupt RNA splicing, with adult-onset symptoms typically appearing between ages 20 and 40.
• ▪There are currently no disease-modifying therapies available for myotonic dystrophy type 1, and treatment is limited to symptom management.

Debatable claims

• ▪The lack of existing treatments justifies accepting greater uncertainty in rare disease trials
• ▪The FDA should grant accelerated approval to z-basivarsen for myotonic dystrophy
• ▪Video hand-opening time is an adequate surrogate endpoint for regulatory approval of myotonic dystrophy drugs