Dyne Therapeutics reports ‘positive’ initial data from ACHIEVE trial of DYNE-101

Dyne Therapeutics announced positive initial clinical data from its ACHIEVE trial of DYNE-101 in patients with myotonic dystrophy type 1 and its DELIVER trial of DYNE-251 in patients with Duchenne muscular dystrophy who are amenable to exon 51 skipping. In the ACHIEVE trial, DYNE-101 demonstrated a dose-dependent splicing correction and increase in muscle delivery and DMPK knockdown while also showing functional improvement in myotonia. Key initial findings from ACHIEVE include: Muscle Delivery: Administration of 3.4 mg/kg of DYNE-101 Q4W demonstrated a mean ASO muscle concentration of 21.5 ng/g at 3 months, while administration of 1.8 mg/kg Q4W showed a mean ASO muscle concentration of 10.0 ng/g at 3 months. DMPK Knockdown: Evaluable patients in the 3.4 mg/kg Q4W group had a 40% mean DMPK knockdown from baseline compared to 25% in patients in the 1.8 mg/kg Q4W group at 3 months. Splicing: Evaluable patients treated with 3.4 mg/kg Q4W of DYNE-101 had a 19% mean splicing correction from baseline across a broad, 22-gene panel at 3 months, with all evaluable participants experiencing an improvement. Patients in the 1.8 mg/kg Q4W group at 3 months had a 13% mean splicing correction. Function: Patients treated with 1.8 mg/kg of DYNE-101 Q4W had a mean 3.8 second benefit in myotonia at 6 months as measured by video hand opening time. Myotonia, which is difficulty in relaxing muscles, is a common symptom of DM1 patients. Patient Reported Outcome: Patients in the DYNE-101 1.8 mg/kg Q4W group experienced an overall improvement at 6 months in the Myotonic Dystrophy Health Index, including the fatigue subscale, suggesting potential benefit of DYNE-101 in the CNS.