Late Breaking: Interim Analysis of Evolve: Evaluating Eteplirsen, Golodirsen, or Casimersen Treatment in Patients <7 Years Old in Routine Clinical Practice



Poster Number: 211


Shannon Grabich, PhD, MS, Sarepta Therapeutics, Inc., Sourav Santra, Sarepta Therapeutics, Inc., Megan Waldrop, MD, Center for Gene Therapy, Nationwide Children's Hospital and Ohio State University Wexner Medical Cen, Katherine Mathews, MD, FAAN, The University of Iowa, Farida Abid, MD, Texas Children’s Hospital, Leigh Maria Ramos-Platt, MD, Children’s Hospital Los Angeles and Keck School of Medicine University of Southern California, Rebecca Scharf, UVA Children's Hospital, Craig Zaidman, MD, Washington University School of Medicine, Ihor Sehinovych, PharmD, Sarepta Therapeutics, Inc., Craig McDonald, MD, University of California, Davis

Current clinical recommendations for Duchenne muscular dystrophy (DMD) emphasize the importance of early diagnosis and treatment. Study 4658-102 (NCT03218995) demonstrated the safety and tolerability of eteplirsen in the youngest population of patients with DMD (6 to 48 months) in a clinical trial. Here, patients’ (<84 months old) experience with phosphorodiamidate morpholino oligomer (PMO) treatment (eteplirsen, golodirsen, or casimersen) in routine clinical practice is described for the first time from the ongoing phase 4, observational, EVOLVE study. Methods Patients were stratified by age at PMO treatment initiation: <24, 24 to <48, and 48 to <84 months. The interim analysis included steroid use, treatment duration, safety, and loss of ambulation. Results As of December 2021, 32 patients <84 months were enrolled; eteplirsen-treated (n=30): mean (SD) age (years) at treatment initiation was 1.8 (0.05), 3.3 (0.42), and 5.7 (0.74), and mean (SD) treatment duration (years) was 2.5 (1.45), 2.8 (1.66), and 4.6 (1.54) for the <24, 24 to <48, and 48 to <84-month-old groups, respectively. Steroid usage before eteplirsen initiation was 0/3, 1/7 (14%), and 12/20 (60%) for the 3 age groups. Three serious adverse events (SAEs) occurred in 2/30 (6.7%) eteplirsen-treated patients; none were determined to be treatment related. Eteplirsen was well tolerated with no treatment-related discontinuations or treatment interruptions. Two patients, 1 golodirsen-treated and 1 casimersen-treated patient, were enrolled (ages 6.4 and 6.2 at treatment initiation, respectively; treatment duration was 0.7 years for each). Neither had prior steroid use or SAEs reported. Conclusion These real-world data are consistent with the safety of previous clinical studies and add to the body of evidence supporting the early initiation of treatment with PMO therapy in patients <7 years old.