Intravenous and Intrathecal Onasemnogene Abeparvovec Gene Therapy in Symptomatic and Presymptomatic Spinal Muscular Atrophy: Long-Term Follow-Up Study


Clinical Trials

Poster Number: 153


Anne Connolly, Center for Gene Therapy, Nationwide Children’s Hospital, Eugenio Mercuri, MD, PhD, Department of Paediatric Neurology and Nemo Clinical Centre, Catholic University, Kevin A. Strauss, MD, Clinic for Special Children, John Day, MD, PhD, Stanford University, Yin-Hsiu Chien, MD, National Taiwan University Hospital, Riccardo Masson, MD, Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy, Melissa Wigderson, Novartis Gene Therapies, Inc., Iulian Alecu, Novartis Pharmaceuticals, Nicolas Ballarini, Novartis Pharmaceuticals, Lesa Mehl, Novartis Institutes for BioMedical Research, Jonathan Marra, Novartis Pharmaceuticals, Basil Darras, MD, Department of Neurology, University of Pittsburgh, Pittsburgh, PA

Objective: Examine the long-term safety and durability of intravenous or intrathecal onasemnogene abeparvovec in symptomatic and presymptomatic patients with spinal muscular atrophy (SMA) who enrolled into the LT-002 study (NCT04042025).
Background: Patients who received intravenous (STR1VE-US; STR1VE-EU; STR1VE-AP; SPR1NT) and intrathecal (STRONG) onasemnogene abeparvovec demonstrated improved survival and motor function versus natural history.
Methods: Long-term safety was assessed by medical history/record review, physical examination, laboratory evaluation, and pulmonary/cardiac assessments. Efficacy was assessed by developmental milestones and Hammersmith Functional Motor Scale Expanded (HFMSE).
Results: As of May 23, 2022, 81 patients (intravenous, n=63 [symptomatic, n=38; presymptomatic, n=25]; intrathecal, n=18) were enrolled in LT-002, with a mean (range) follow-up of 3.4 (1.0–4.3) and 3.6 (2.6–4.3) years for the intravenous and intrathecal cohorts, respectively. There were no deaths or treatment-emergent adverse events (TEAEs) resulting in discontinuation. The most frequently reported TEAEs were gastroenteritis, nasopharyngitis, pneumonia, respiratory distress, and viral infection. All patients survived and maintained developmental milestones with a mean (range) age at cutoff of 3.7 (2.4–4.7) and 5.3 (3.4–7.4) years for the intravenous and intrathecal cohorts, respectively. Only one patient required permanent ventilation. Twenty-seven patients achieved new developmental milestones (presymptomatic-intravenous, n=6; symptomatic-intravenous, n=16; intrathecal, n=5); more than half (n=16) did so without add-on therapy. Improvements in HFMSE were clinically significant (≥3 points; presymptomatic-intravenous, 81.25%; symptomatic-intravenous, 66.6%; intrathecal, 50%). No patients treated presymptomatically required ventilatory/nutritional support; few symptomatic patients required ventilatory (intravenous-symptomatic, 32%; intrathecal, 5.6%) or feeding (intravenous-symptomatic, 20%; intrathecal, 0%) support at cutoff. Most patients fed orally (intravenous, 95%; intrathecal, 100%). The majority (57/81) never received add-on therapy. Of those receiving add-on therapy, half did not achieve a new developmental milestone after initiation of add-on therapy.
Conclusions: Intravenous/intrathecal onasemnogene abeparvovec demonstrates consistent, substantial, and durable efficacy and no new safety signals in symptomatic and presymptomatic patients with SMA.