P211 Intravenous and intrathecal onasemnogene abeparvovec gene therapy in symptomatic and presymptomatic spinal muscular atrophy (SMA): long-term follow-up study

We examined the long-term safety and durability of intravenous or intrathecal onasemnogene abeparvovec in symptomatic and presymptomatic patients with SMA in the LT-002 study. Safety was assessed by medical history/record review, physical examination, laboratory evaluation, and pulmonary/cardiac assessments. Efficacy was assessed by developmental milestones and HFMSE. As of May 23, 2022, 81 patients (intravenous, n=63 [symptomatic, n=38; presymptomatic, n=25]; intrathecal, n=18) were enrolled. Mean (range) follow-up was 3.4 (1.0–4.3) and 3.6 (2.6–4.3) years for the intravenous and intrathecal cohorts, respectively. No deaths or treatment-emergent adverse events (TEAEs) causing discontinuation occurred. The most frequently reported TEAEs were gastroenteritis, nasopharyngitis, pneumonia, respiratory distress, and viral infection. All patients survived and maintained developmental milestones. Mean (range) age was 3.7 (2.4–4.7) and 5.3 (3.4–7.5) years for the intravenous and intrathecal cohorts, respectively. One patient required permanent ventilation. Twenty-seven patients achieved new milestones (presymptomatic-intravenous, n=6; symptomatic-intravenous, n=16; intrathecal, n=5); more than half (n=16) did so without add-on therapy. HFMSE improvements were clinically significant (≥3 points; presymptomatic-intravenous, 81.25%; symptomatic-intravenous, 66.7%; 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. Most fed orally (intravenous, 92.1%; intrathecal, 100%). The majority (57/81) never received add-on therapy; of those who did, half did not achieve new milestones. Intravenous/intrathecal onasemnogene abeparvovec demonstrates consistent, substantial, and durable efficacy and no new safety signals in symptomatic and presymptomatic patients with SMA. We examined the long-term safety and durability of intravenous or intrathecal onasemnogene abeparvovec in symptomatic and presymptomatic patients with SMA in the LT-002 study. Safety was assessed by medical history/record review, physical examination, laboratory evaluation, and pulmonary/cardiac assessments. Efficacy was assessed by developmental milestones and HFMSE. As of May 23, 2022, 81 patients (intravenous, n=63 [symptomatic, n=38; presymptomatic, n=25]; intrathecal, n=18) were enrolled. Mean (range) follow-up was 3.4 (1.0–4.3) and 3.6 (2.6–4.3) years for the intravenous and intrathecal cohorts, respectively. No deaths or treatment-emergent adverse events (TEAEs) causing discontinuation occurred. The most frequently reported TEAEs were gastroenteritis, nasopharyngitis, pneumonia, respiratory distress, and viral infection. All patients survived and maintained developmental milestones. Mean (range) age was 3.7 (2.4–4.7) and 5.3 (3.4–7.5) years for the intravenous and intrathecal cohorts, respectively. One patient required permanent ventilation. Twenty-seven patients achieved new milestones (presymptomatic-intravenous, n=6; symptomatic-intravenous, n=16; intrathecal, n=5); more than half (n=16) did so without add-on therapy. HFMSE improvements were clinically significant (≥3 points; presymptomatic-intravenous, 81.25%; symptomatic-intravenous, 66.7%; 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. Most fed orally (intravenous, 92.1%; intrathecal, 100%). The majority (57/81) never received add-on therapy; of those who did, half did not achieve new milestones. Intravenous/intrathecal onasemnogene abeparvovec demonstrates consistent, substantial, and durable efficacy and no new safety signals in symptomatic and presymptomatic patients with SMA.