Intrathecal onasemnogene abeparvovec for treatment-experienced patients with spinal muscular atrophy: a phase 3b, open-label trial
Jennifer M. Kwon, Francina Munell, Laure Le Goff, Kotaro Yuge, Tamaki Kato, Claude Cancés, Liesbeth De Waele, Ian Woodcock, Eugenio Mercuri, Crystal M. Proud, Basil T. Darras, Leslie H. Hayes, Maryam Oskoui, Jeannie Visootsak, Gemma Williams, Andreja Ilić, Lina Yang, W. Ludo van der Pol
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 .