LB: Zeleciment rostudirsen led to trends in long-term improvement in clinical outcomes including cardiopulmonary function: Additional data from DELIVER

Topic:

Clinical Trials

Poster Number: 476 LBT

Author(s):

Chamindra Laverty, MD, UC San Diego Health, Susan Apkon, Children’s Hospital Colorado, Liesbeth De Waele, MD PhD, University Hospitals Leuven, Kevin Flanigan, MD, Nationwide Children's Hospital, Hugh McMillan, MD, Children's Hospital of Eastern Ontario, Marika Pane, MD, Fondazione Policlinico Universitario A. Gemelli, 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, Prashant Bansal, Dyne Therapeutics, 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 

DMD is a multisystem disease that affects skeletal, pulmonary, and cardiac muscles as well as the brain and GI tract. Individuals with DMD exhibit progressive muscle weakness and loss of ambulation, ultimately succumbing to cardiorespiratory failure. Therefore, preserving cardiopulmonary function is necessary for prolonging survival in DMD.

Zeleciment rostudirsen (z-rostudirsen, also known as DYNE-251) leverages TfR1 to deliver an exon 51 skipping PMO to muscle with the goal of producing near-full length functional dystrophin. In the MAD portion of the 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. After the placebo-controlled period, participants entered an OLE/LTE and transitioned to 20 mg/kg Q4W, as applicable.

Data from the LTE portion of DELIVER showed sustained improvements from baseline through 24 months in multiple clinical endpoints of muscle function, including TTR velocity, 10MWR velocity, NSAA, SV95C, and PUL2.0. Improvement over 24 months was also noted in FVC%p, suggesting long-term benefit in lung function with z-rostudirsen. Cardiac magnetic resonance (CMR) measurement of circumferential strain, a sensitive marker of myocardial fiber shortening, showed consistent improvement over 24 months and may serve as an early signal of preserved contractile quality. CMR-based left ventricular ejection fraction showed trends toward stabilization at 12 months followed by a modest gain through month 24. 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.

Long-term data from the DELIVER trial suggest trends in improvement in muscle function and potential preservation of cardiopulmonary function upon treatment with z-rostudirsen. Additional long-term data are needed to confirm the cardiopulmonary effects.