2025 Interim Analysis of EVOLVE: A Long-term Observational Study Evaluating Eteplirsen, Golodirsen, or Casimersen in Routine Clinical Practice

Topic:

Other

Poster Number: 25 S

Author(s):

Cuixia Tian, MD, Cincinnati Children’s Hospital Medical Center, Ashutosh Kumar, MD, Penn State Health Milton S. Hershey Medical Center, Katherine Mathews, MD, University of Iowa, Iowa City, Iowa, USA, Sourav Santra, PhD, Sarepta Therapeutics, Inc., Shane Hornibrook, Sarepta Therapeutics, Inc., Kerri Drummond, RN, Sarepta Therapeutics, Inc., Jessica Wise, MPH, Sarepta Therapeutics, Inc., Shannon Grabich, PhD, Sarepta Therapeutics, Inc., Seth J. Perlman, MD, Seattle Children's, Rebecca J. Scharf, MD, MPH, University of Virginia (UVA) Children’s Hospital, Craig McDonald, MD, University of California Davis Health

Background: EVOLVE (NCT06606340)—a phase 4, multicenter, observational study—is prospectively assessing long-term functional and clinical outcomes of patients with Duchenne muscular dystrophy treated with phosphorodiamidate morpholino oligomers (PMOs) including eteplirsen, golodirsen, or casimersen, which received accelerated FDA approval in 2016, 2019, and 2021, respectively.

Objectives: To present safety and loss of ambulation (LOA) data as observed in EVOLVE.

Methods: Treatment-emergent serious adverse events (TESAEs) and LOA were reported for patients receiving eteplirsen, golodirsen, or casimersen. Adverse events and patients’ ambulatory status were summarized descriptively; Kaplan-Meier (KM) curves were used to assess time to LOA from treatment initiation. Treatment discontinuation was defined by the number of patients that stopped treatment as of last available visit.

Results: As of February 2025, 173 patients were enrolled in EVOLVE with mean (SD) age (y) by PMO: eteplirsen, 14.0 (5.5; n=126); golodirsen, 13.4 (4.2; n=25); and casimersen, 16.4 (5.9; n=22). At the time of the interim analysis, the mean (SD) duration of treatment was 7.1 (2.2) y for eteplirsen, 3.2 (1.5) y for golodirsen, and 2.9 (0.9) y for casimersen. All PMOs showed favorable safety profiles and were well tolerated; no TESAEs were deemed treatment related. Overall exposure-adjusted incidence rates among all TESAEs per 100 patient-years (PY) were as follows: eteplirsen, 10.5 PY; golodirsen, 4.0 PY; casimersen, 23.0 PY. Of the 126 eteplirsen patients, 85 (67%) were ambulatory at initiation and 38 (30%) lost ambulation after starting treatment, with a median age at LOA of 15.8 y and median time to LOA of 9.1 y. In the golodirsen group, 13 of 25 patients (52%) were ambulatory at treatment initiation and 6 (24%) lost ambulation after treatment initiation. Of the 22 casimersen patients, 8 (36%) were ambulatory at treatment initiation and none lost ambulation after treatment initiation. KM analyses for golodirsen and casimersen were not reported due to limited follow-up and ongoing enrollment. Treatment discontinuation was low across all groups (eteplirsen, 6.3%; golodirsen, 28%; casimersen, 0%).

Conclusions: This interim analysis supports real-world safety of PMOs and high rate of continuation over time. EVOLVE continues to observe the potential impact eteplirsen, golodirsen, and casimersen have on meaningful clinical outcomes, such as LOA.