Safety and Efficacy from the Ongoing Phase 1/2 DELIVER Trial of DYNE-251 in Males with DMD Mutations Amenable to Exon 51 Skipping

Topic:

Clinical Trials

Poster Number: O83

Author(s):

Han Phan, MD, Rare Disease Research, Atlanta, Georgia, USA, Craig Campbell, Dr., London Health Sciences Centre, London, Ontario, Canada, Nicolas Deconinck, Prof. Dr., Neuromuscular Reference Center UZ Gent, Gent, Belgium, Liesbeth De Waele, Prof. Dr., University Hospitals Leuven, Leuven, Belgium, Kevin Flanigan, MD, Nationwide Children's Hospital, Columbus, Michelle Lorentzos, BA MBBS PhD FRACP, Children's Hospital at Westmead, Westmead, New South Wales, Australia, Perry Shieh, MD, UCLA, Chris Mix, MD, Dyne Therapeutics, Soma Ray, PhD, Dyne Therapeutics, Dazhe Wang, Dyne Therapeutics, Inc., Waltham, MA, USA, Ashish Dugar, PhD, MBA, Dyne Therapeutics, Douglas Kerr, MD/PhD/MBA, Dyne Therapeutics, Maria Naylor, PhD, Dyne Therapeutics, Michela Guglieri, MD, Newcastle University, Newcastle upon Tyne, England, UK

DMD is caused by absence of functional dystrophin protein. DYNE-251, an investigational therapeutic for DMD, leverages the transferrin receptor 1 to deliver an exon 51-skipping PMO to affected tissues with the goal of restoring dystrophin expression. Safety and efficacy of DYNE-251 are investigated in the Phase 1/2 DELIVER trial (NCT05524883) in 4-16-year-old males with exon 51-skipping amenable DMD mutations. In the MAD portion of DELIVER, participants are randomized to receive DYNE-251 or placebo Q4W or Q8W for 6 months; participants subsequently enter the OLE/LTE. All 54 enrolled participants are at the 20 mg/kg dose level.

DYNE-251 drove dose-dependent increases in mean PMO muscle concentration and exon skipping, resulting in 3.22% and 3.72% of normal mean dystrophin in the 10 mg/kg and 20 mg/kg cohorts, respectively, at 6 months. The mean corresponding muscle content-adjusted dystrophin levels were 7.64% and 8.72% of normal. DYNE-251 led to improvements across multiple functional endpoints, including the North Star Ambulatory Assessment, Time to Rise from Floor, 10-Meter Walk/Run Test, and Stride Velocity 95th Centile. Improvements were noted as of 6 months in the 10 mg/kg and 20 mg/kg cohorts, with a continued effect through 12 months in the 10 mg/kg cohort. DYNE-251 had a favorable safety profile as of the analysis date with most TEAEs reported as mild or moderate. Three serious TEAEs potentially related to study drug occurred in two participants in a 40 mg/kg Q4W cohort. These events had multiple confounding factors suggestive of infection or background risk that may have contributed to their presentation. Subsequently, all participants in the 40 mg/kg cohorts were lowered to the 20 mg/kg dose level.

DYNE-251 had a favorable safety profile and resulted in early improvements across multiple functional endpoints. Longer-term follow-up data for patients included in this abstract will be presented.