Zeleciment rostudirsen significantly increased dystrophin protein levels and led to functional improvement in clinical measures in the DELIVER trial

Topic:

Clinical Trials

Poster Number: 442 O

Author(s):

Kevin Flanigan, MD, Nationwide Children's Hospital, Nicolas Deconinck, Neuromuscular Reference Center, Liesbeth De Waele, MD PhD, University Hospitals Leuven, Chamindra Laverty, MD, UC San Diego Health, Jeehun Lee, Samsung Medical Center and Sungkyunkwan university, Hugh McMillan, MD, Children's Hospital of Eastern Ontario, Stefano C. Previtali, IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Perry Shieh, MD, University of California Los Angeles, Ian Woodcock, MD, PhD, Murdoch Children’s Research Institute, Parkville, Victoria and The Royal Children’s Hospital, Soma Ray, PhD, Dyne Therapeutics, Dazhe Wang, Dyne Therapeutics, Douglas Kerr, MD/PhD/MBA, Dyne Therapeutics, Maria Naylor, PhD, Dyne Therapeutics, Michela Guglieri, MD, Newcastle University, Newcastle upon Tyne, England, UK 

Individuals with DMD pathogenic variants amenable to exon 51 skipping have significant unmet needs, despite approved treatments. Zeleciment rostudirsen (z-rostudirsen, also known as DYNE-251) leverages the transferrin receptor, TfR1, to deliver an exon 51 skipping PMO to muscle with the goal of producing near-full length functional dystrophin.
In the Multiple Ascending Dose (MAD) portion of the Phase 1/2 DELIVER trial (NCT05524883), 54 participants received z-rostudirsen or placebo every 4 or 8 weeks for 6 months. Following dose selection, 32 participants were randomized 3:1 to receive 20 mg/kg Q4W z-rostudirsen or placebo for 6 months in a registrational expansion cohort (REC). After the placebo-controlled period, participants entered an OLE/LTE and transitioned to 20 mg/kg Q4W, as applicable.
The REC met its primary endpoint, demonstrating a statistically significant increase in mean muscle content-adjusted dystrophin at 6 months compared to baseline (5.46% vs. 0.83% of normal, respectively, p<0.0001). Trends in functional improvement were observed across multiple clinical endpoints at 6 months including TTR velocity, 10MWR velocity, NSAA, SV95C, PUL2.0, and FVC%p. Sustained improvements from baseline in these measures were also observed through 18 months of treatment in participants who enrolled in the MAD at 20 mg/kg Q4W and through 24 months of treatment in participants who enrolled in the MAD at 10 mg/kg Q4W and transitioned to 20 mg/kg Q4W in the OLE/LTE. As of August 19, 2025, z-rostudirsen had a favorable safety and tolerability profile based on data from 86 participants enrolled in DELIVER and followed for up to 36 months. Data from the DELIVER trial, including robust dystrophin expression, trends in functional improvement, favorable safety profile, and convenient dosing support the potential of z-rostudirsen to address the unmet needs of individuals with DMD pathogenic variants amenable to exon 51 skipping.