DYNE-251 for DMD Yields Promising Biomarker, Functional Results in Early-Stage Trial

Patients with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping demonstrated unprecedented dystrophin expression and functional improvement with the investigational therapeutic DYNE-251, according to clinical data from an ongoing phase 1/2 trial announced by Dyne Therapeutics Inc.

“In DELIVER, DYNE-251 achieved the highest level of dystrophin expression reported for an exon 51 skipping therapy and improvement in multiple functional endpoints across multiple cohorts that continued with time on therapy,” said Wildon Farwell, MD, MPH, chief medical officer of Dyne.

The update included 6-month biomarker and functional data for 8 patients in a 20 mg/kg cohort and 12-month functional data for 6 patients in a 10 mg/kg cohort. According to the company, DYNE-251 demonstrated dose-dependent exon skipping and dystrophin expression and improvement in multiple functional endpoints in both cohorts.

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Among the findings, the mean absolute dystrophin expression among patients treated with 20 mg/kg every 4 weeks (Q4W) was 3.71% of normal without adjustment for muscle content. The finding was 10-fold higher than the 0.3% reported with the weekly standard-of-care eteplirsen, Dyne noted. After adjustment for muscle content, patients treated with DYNE-251 achieved mean absolute dystrophin of 8.72%.

Additionally, patients in both the 20 mg/kg and 10 mg/kg Q4W groups showed meaningful gains in multiple functional endpoints, including North Star Ambulatory Assessment, 10-Meter Walk/Run Time, Time to Rise from Floor, and the Stride Velocity 95th Centile (SV95C). SVC95C is a digital outcome measure of ambulatory performance in a patient’s normal daily environment used as a primary endpoint for DMD clinical trials in Europe.

The drug also demonstrated a favorable safety profile, with most treatment-emergent adverse events being mild or moderate. At the 40 mg/kg dose level, 2 participants did experience serious treatment-emergent adverse events potentially related to the treatment. Both patients have recovered, according to Dyne.

“With these exciting data, we are moving quickly to initiate registrational cohorts in DELIVER,” Dr Farwell said, “and we continue to pursue expedited approval pathways and plan to provide an update on our path to registration by the end of this year.”

Reference

Dyne Therapeutics announces new clinical data from phase 1/2 DELIVER trial of DYNE-251 in Duchenne muscular dystrophy demonstrating unprecedented dystrophin expression and functional improvement in multiple cohorts. News release. Dyne Therapeutics Inc.; September 3, 2024. Accessed September 9, 2024.