Intrathecal onasemnogene abeparvovec for treatment-experienced patients with spinal muscular atrophy: a phase 3b, open-label trial

Intrathecal onasemnogene abeparvovec (OAV101 IT) may enable a one-time gene transfer therapy, addressing an unmet need across the broader spinal muscular atrophy (SMA) population. STRENGTH ( NCT05386680 ) was a 52-week, phase 3b, single-arm, open-label, multicenter study evaluating OAV101 IT in participants with SMA aged 2 to <18 years who discontinued nusinersen or risdiplam. The primary objective was safety/tolerability. Twenty-seven participants were enrolled (mean (s.d.) age at OAV101 IT, 7.4 (3.35) years; range, 2.4-17.7 years) with prior nusinersen or risdiplam (mean (s.d.) duration of 4.3 (1.07) years; range, 1.86-6.18 years or 3.0 (2.02); range, 0.39-6.28 years). All (n = 27) experienced at least one adverse event (AE), most frequently nasopharyngitis (n = 15, 55.6%), pyrexia (n = 14, 51.9%) and vomiting (n = 13, 48.1%). Thirteen participants (48.1%) experienced treatment-related AEs, most frequently vomiting (n = 6, 22.2%), headache (n = 4, 14.8%) and pyrexia (n = 3, 11.1%). Serious adverse events (SAEs) were reported for four participants (n = 4, 14.8%) (mostly respiratory infection related). No AEs leading to death or study discontinuation were reported. Adverse events of special interest (AESI) reported were in categories of transient thrombocytopenia (n = 8, 29.6%), hepatotoxicity (n = 4, 14.8%) and signs and symptoms that may be suggestive of dorsal root ganglia toxicity (n = 2, 7.4%). The OAV101 IT safety profile was consistent with findings in treatment-naïve patients. Trial registration: ClinicalTrials.gov identifier: NCT05386680 .

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Publication Details

Journal
Nature Medicine
Published
2025-12-08
DOI
https://doi.org/10.1038/s41591-025-04119-2
Citations
4
Primary Topic
Neurogenetic and Muscular Disorders Research
Type
article
Field-Weighted Citation Impact
6.50

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article

Intrathecal onasemnogene abeparvovec for treatment-experienced patients with spinal muscular atrophy: a phase 3b, open-label trial

Francina Munell, Claude Cancés, W. Ludo van der Pol, Jeannie Visootsak et al.
4 citations
Nature Medicine
Neurogenetic and Muscular Disorders Research
6.50
article

Intrathecal onasemnogene abeparvovec for treatment-experienced patients with spinal muscular atrophy: a phase 3b, open-label trial

Francina Munell, Claude Cancés, W. Ludo van der Pol, Jeannie Visootsak, Leslie H. Hayes, Liesbeth De Waele, Maryam Oskoui, Eugenio Maria Mercuri, Aleksandra Ilić, Tamaki Kato, Laure Le Goff, Gemma Williams, Kotaro Yuge, Crystal M. Proud, Jennifer M. Kwon, Basil T. Darras, Ian R. Woodcock, Lina Yang
article en
4 citations

Abstract

Intrathecal onasemnogene abeparvovec (OAV101 IT) may enable a one-time gene transfer therapy, addressing an unmet need across the broader spinal muscular atrophy (SMA) population. STRENGTH ( NCT05386680 ) was a 52-week, phase 3b, single-arm, open-label, multicenter study evaluating OAV101 IT in participants with SMA aged 2 to <18 years who discontinued nusinersen or risdiplam. The primary objective was safety/tolerability. Twenty-seven participants were enrolled (mean (s.d.) age at OAV101 IT, 7.4 (3.35) years; range, 2.4-17.7 years) with prior nusinersen or risdiplam (mean (s.d.) duration of 4.3 (1.07) years; range, 1.86-6.18 years or 3.0 (2.02); range, 0.39-6.28 years). All (n = 27) experienced at least one adverse event (AE), most frequently nasopharyngitis (n = 15, 55.6%), pyrexia (n = 14, 51.9%) and vomiting (n = 13, 48.1%). Thirteen participants (48.1%) experienced treatment-related AEs, most frequently vomiting (n = 6, 22.2%), headache (n = 4, 14.8%) and pyrexia (n = 3, 11.1%). Serious adverse events (SAEs) were reported for four participants (n = 4, 14.8%) (mostly respiratory infection related). No AEs leading to death or study discontinuation were reported. Adverse events of special interest (AESI) reported were in categories of transient thrombocytopenia (n = 8, 29.6%), hepatotoxicity (n = 4, 14.8%) and signs and symptoms that may be suggestive of dorsal root ganglia toxicity (n = 2, 7.4%). The OAV101 IT safety profile was consistent with findings in treatment-naïve patients. Trial registration: ClinicalTrials.gov identifier: NCT05386680 .

Nature MedicineVol. 32(2)
Università Cattolica del Sacro Cuore (IT), Kurume University (JP), Novartis (Switzerland) (CH), Boston Children's Hospital (US), Royal Children's Hospital (AU), Harvard University (US), Université Fédérale de Toulouse Midi-Pyrénées (FR), McGill University Health Centre (CA), University Medical Center Utrecht (NL), Hôpital Femme Mère Enfant (FR), Centro Clinico Nemo (IT), Novartis (United States) (US), Vall d'Hebron Hospital Universitari (ES), Novartis (United Kingdom) (GB), Tokyo Women's Medical University (JP), University of Wisconsin American Family Children's Hospital (US), Children's Hospital of The King's Daughters (US), Murdoch Children's Research Institute (AU), McGill University (CA), KU Leuven (BE)
Novartis Pharma
Openalex Percentile: Top 3%
Neurogenetic and Muscular Disorders Research
6.50
DOIOpen Access PDFOpenAlex
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