Announcement • May 22
Dyne Therapeutics Announces Initiation of Phase 3 Forzetto Trial of Z-Rostudirsen in Duchenne Muscular Dystrophy
Dyne Therapeutics, Inc. announced the initiation of the Phase 3 FORZETTO trial of zeleciment rostudirsen (z-rostudirsen, also known as DYNE-251), in individuals with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping. The design of the FORZETTO trial will be presented at the 19th International Congress on Neuromuscular Diseases (ICNMD) being held July 7-11, 2026, in Florence, Italy. FORZETTO is a global, randomized, placebo-controlled, double-blind, confirmatory Phase 3 trial designed to assess the efficacy, safety, and tolerability of z-rostudirsen administered intravenously to ambulatory male participants with DMD amenable to exon 51 skipping. The trial will enroll approximately 90 participants 4 to 18 years of age who will be randomized 1:1 to receive 20 mg/kg of z-rostudirsen or placebo every four weeks. The first trial site is activated and open to enrollment. The primary endpoint is the change from baseline in rise from floor (RFF) velocity, also referred to as time to rise (TTR) velocity, at Week 73. RFF velocity is a clinically meaningful measure of muscle strength and motor coordination commonly assessed in DMD clinical trials. In the registrational expansion cohort of the Phase 1/2 DELIVER trial, treatment with z-rostudirsen 20 mg/kg every four weeks (n=21) led to an improvement in RFF velocity at 6 months of 0.04 rise/sec compared to pooled placebo (n=18; nominal p1, exceeding the published minimal clinically important difference (MCID)2, along with a favorable safety profile. Secondary endpoints in the FORZETTO trial include changes from baseline in stride velocity 95th centile (SV95C), North Star Ambulatory Assessment (NSAA) total score, 10-meter walk/run (10MWR) velocity, four-stair climb (4SC) velocity and forced vital capacity percent predicted (FVC%p), as well as additional functional and patient-reported outcome measures. Following the 72-week double-blind placebo-controlled treatment period, participants will be eligible to enroll in a 96-week open-label long-term extension. Dyne has aligned with the U.S. Food and Drug Administration (FDA) on the FORZETTO Phase 3 trial design and protocol. FORZETTO is intended to serve as a confirmatory trial to support the potential conversion of Accelerated Approval to traditional approval in the U.S. and to support ex-U.S. marketing applications. The FORZETTO Phase 3 study design reflects the company's commitment to patient-centered drug development, with the goal of delivering functional improvement for people living with genetically driven neuromuscular diseases. The poster presentation will be available in the Scientific Publications & Presentations section of Dyne’s website at the commencement of the poster session. FORZETTO is a global, randomized, placebo-controlled, double-blind, confirmatory Phase 3 clinical trial evaluating the efficacy, safety and tolerability of zeleciment rostudirsen (z-rostudirsen, also known as DYNE-251) in ambulatory male participants with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping. The trial will enroll approximately 90 participants 4 to 18 years of age who will receive 20 mg/kg of z-rostudirsen or placebo once every four weeks for 72 weeks. Participants who complete the placebo-controlled period may enter a long-term extension and receive 20 mg/kg of z-rostudirsen once every four weeks for up to an additional 96 weeks. The primary endpoint of FORZETTO is the change from baseline in rise from floor (RFF) velocity at Week 73. RFF velocity is a clinically meaningful measure of muscle strength and motor coordination commonly assessed in DMD clinical trials. Secondary endpoints include changes from baseline in stride velocity 95th centile (SV95C), North Star Ambulatory Assessment (NSAA) total score, 10-meter walk/run (10MWR) velocity, four-stair climb (4SC) velocity and forced vital capacity percent predicted (FVC%p), as well as additional functional and patient-reported outcome measures. Z-rostudirsen is an investigational therapeutic for individuals with DMD who have mutations in the DMD gene that are amenable to exon 51 skipping. The registrational expansion cohort of the global Phase 1/2 DELIVER clinical trial of z-rostudirsen met its primary endpoint. Data from the DELIVER trial will serve as the basis for a planned Biologics License Application (BLA) for potential U.S. Accelerated Approval. Z-rostudirsen continues to be evaluated in the long-term extension portion of the DELIVER trial and in the global confirmatory Phase 3 FORZETTO clinical trial. Z-rostudirsen consists of a phosphorodiamidate morpholino oligomer (PMO) conjugated to an antigen-binding fragment (Fab) that binds to the transferrin receptor 1 (TfR1). It is designed to enable the production of near full-length dystrophin in muscle and the central nervous system (CNS) to provide functional improvement. Z-rostudirsen has received Breakthrough Therapy, Fast Track and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA), as well as Orphan Drug designation from the FDA, European Medicines Agency (EMA) and the Ministry of Health, Labour and Welfare (MHLW) in Japan for the treatment of individuals with DMD amenable to exon 51 skipping. In addition to z-rostudirsen, Dyne is building a DMD franchise and has preclinical programs targeting other exons, including DYNE-253, DYNE-245, DYNE-244 and DYNE-255. Duchenne muscular dystrophy (DMD) is a rare X-linked progressive neuromuscular disorder caused by mutations in the DMD gene. These mutations result in a complete or near-complete absence of dystrophin, a protein critical for maintaining muscle structure and function. DMD is the most common form of childhood-onset muscular dystrophy, affecting approximately 12,000 individuals in the U.S. and 16,000 in the EU. Symptoms typically emerge between ages 3 and 5, beginning with muscle weakness in the upper arms, thighs and pelvic region, and progressively impacting the lower limbs, forearms, neck and trunk. In addition to physical decline, individuals may experience cognitive impairment and neuropsychiatric challenges such as intellectual disabilities, learning difficulties and behavioral disorders. Despite existing therapies, there remains a significant unmet need for new treatment options that deliver functional improvement.
