Interim analysis of EVOLVE: Evaluating eteplirsen treatment in nonambulatory patients in routine clinical practice from a phase 4 observational study


Clinical Trials

Poster Number: M180


Shannon Grabich, PhD, MS, Sarepta Therapeutics, Megan A. Waldrop, MD, Nationwide Children's Hospital and Ohio State University Wexner Medical Center, Sourav Santra, PhD, Serepta Therapeutics, Inc., Shane Hornibrook, Sarepta Therapeutics, Inc., Ihor Sehinovych, PharmD, Sarepta Therapeutics, Rebecca J. Scharf, MD, University of Virginia, Katherine Mathews, MD, FAAN, University of Iowa

Progressive muscle damage in Duchenne muscular dystrophy (DMD) leads to decline in upper limb strength and function. Although eteplirsen has been shown to attenuate ambulatory and pulmonary decline vs external controls, accumulation of data in more advanced patient populations allows further understanding of treatment impact. Here, safety and clinical outcomes, including upper limb function in eteplirsen-treated nonambulatory patients with DMD, are described from the ongoing real-world, phase 4, multicenter, observational EVOLVE study.
This interim analysis included patients who were nonambulatory at eteplirsen treatment initiation or became nonambulatory after eteplirsen initiation. Treatment duration, safety, and Brooke upper extremity scores are described.
Of 123 eteplirsen-treated patients enrolled in EVOLVE as of December 2021, 41 (33%) were nonambulatory at treatment initiation (mean age: 18.4 [range, 10.628.6] years; mean [SD] duration of treatment: 4.2 [1.2] years). Thirty-one (25%) patients lost ambulation after eteplirsen initiation (mean age: 14.7 [range, 7.223.2] years; mean [SD] duration of treatment: 6.1 [1.9] years). At the time of the analysis, all patients that either were nonambulatory at treatment initiation or lost ambulation after eteplirsen initiation (n=72), persisted on eteplirsen (mean [SD] duration of treatment: 5.0 [1.8] years; mean duration of follow-up in EVOLVE: 1.1 [0.8] years). Upper limb function in patients with ≥2 Brooke score evaluations suggested a maintenance of function in 14/18 (78%) of nonambulatory patients and maintenance/improvement of function in 12/15 (80%) of patients who lost ambulation after eteplirsen initiation. The safety profile in nonambulatory patients was consistent with that observed in clinical trials; no treatment-related serious adverse events were observed.
Interim real-world data from a subgroup analysis of nonambulatory EVOLVE patients show persistence of treatment effect and support the safety of eteplirsen. EVOLVE will continue to describe long-term safety and clinical outcomes.