Intrathecal Onasemnogene Abeparvovec for Treatment-Experienced Patients with Spinal Muscular Atrophy: Phase 3b, Open-Label STRENGTH Study

Topic:

Clinical Trials

Poster Number: LB449

Author(s):

Jennifer Kwon, MD MPH, University of Wisconsin School of Medicine and Public Health, Francina Munell, Hospital Vall d’Hebron, Laure Le Goff, Hôpital Femme Mère Enfant - Hospices Civils de Lyon, Kotaro Yuge, Kurume University Hospital, Tamaki Kato, Hospital Clinical Genomics, Tokyo Women’s Medical University, Claude Cances, MD, Toulouse University Hospital Center, Liesbeth De Waele, Prof. Dr., University Hospitals Leuven, Ian R. Woodcock, MBBS, PhD, MSc, The Royal Children’s Hospital, Eugenio M. Mercuri, MD, PhD, Pediatric Neurology Institute, Catholic University and Nemo Pediatrico, Rome, Italy, Crystal Proud, Children’s Hospital of the King’s Daughters, Norfolk, VA, USA, Basil T. Darras, MD, Boston Children’s Hospital, Harvard Medical School, Leslie H. Hayes, MD, Boston Children’s Hospital, Harvard Medical School, Maryam Oskoui, MD, McGill University Health Centre, Jeannie Visootsak, MD, Novartis Pharmaceuticals Corporation, Gemma Williams, Novartis Pharmaceuticals, Andreja Ilic, MA, Novartis Pharmaceuticals, Lina Yang, Novartis Pharmaceuticals Corporation, W. Ludo van der Pol, MD, PhD, University Medical Center Utrecht

Background: Intrathecal onasemnogene abeparvovec (OA) has been studied in treatment-naïve patients with SMA in the phase 1 STRONG (NCT03381729) and phase 3 STEER (NCT05089656) studies. The STRENGTH study evaluated the safety and efficacy of intrathecal OA in treatment-experienced patients with spinal muscular atrophy (SMA).
Objective: STRENGTH (NCT05386680) was a 52-week, phase 3b, single-arm, open-label, multicenter study evaluating safety and efficacy of intrathecal OA for patients with SMA aged 2 to <18 years who were able to sit but never walked independently, and who discontinued nusinersen or risdiplam. The primary objective was to characterize the safety and tolerability of OA. Secondary and exploratory efficacy assessments included motor function (Hammersmith Functional Motor Scale–Expanded [HFMSE], Revised Upper Limb Module [RULM]) and caregiver experience (Assessment of Caregiver Experience in Neuromuscular Disease [ACEND]). Motor milestones were assessed per World Health Organization Multicentre Growth Reference criteria. Results: 27 patients were enrolled (mean [SD] age at OA, 7.4 [3.35] years; n=10, 2–<6 years; n=17, 6–<18 years). Mean duration of prior risdiplam and nusinersen treatment were 3.0 and 4.3 years, respectively. All patients experienced at least one treatment-emergent adverse event (TEAE). The most frequent TEAEs were nasopharyngitis, pyrexia, and vomiting. Serious TEAEs were mostly suggestive of infections. No AEs leading to death or study discontinuation were reported. HFMSE, RULM, and ACEND changes for the overall study population demonstrated stabilization over 52 weeks. The majority of patients demonstrated maintenance of motor milestones or achievement of new milestones. Conclusions: For treatment-experienced patients with SMA who received a one-time intrathecal infusion of OA in STRENGTH, the safety of OA was favorable and consistent with the expected profile. Across motor efficacy assessments, the study population demonstrated stabilization in motor function over 52 weeks.