S61 Onasemnogene abeparvovec gene-replacement therapy (GRT) for spinal muscular atrophy type 1 (SMA1): preliminary pulmonary and ventilatory findings from the phase 3 study (STR1VE)

Introduction and objectives SMA1 is a rapidly progressing neurologic disease caused by biallelic loss/mutation of the survival motor neuron 1 gene (SMN1). Onasemnogene abeparvovec (formerly AVXS-101) is a one-time GRT designed to treat the genetic root cause of SMA by providing immediate, sustained neuronal SMN protein expression. In the phase 1/2a study (NCT02122952), symptomatic SMA1 infants treated with onasemnogene abeparvovec demonstrated exceptional permanent ventilation-free survival, motor milestone achievements, and increased independence from ventilatory and nutritional support. Here we report study design and preliminary pulmonary and bulbar function data from the STR1VE study (NCT03306277). Methods STR1VE is a phase 3, multicenter, open-label, single-arm study in SMA1 patients aged Results Enrollment is complete (N=22 dosed patients). Mean (range) age at symptom onset, genetic diagnosis, and enrollment: 1.9 (0–4.0), 2.6 (0–5.4), and 3.7 (0.5–5.9) months. At baseline, no patient required ventilatory/nutritional support; all exclusively fed by mouth. As of 8 March 2019, 1 patient died due to causes unrelated to onasemnogene abeparvovec (May 2018); 1 withdrew consent. Eighteen of 22 patients had not had any bilevel positive airway pressure (BiPAP) support during the study. All 20 (100%) continuing patients had functional/normal swallowing. Two patients had gastrostomy tubes; 1 who discontinued the study. Eleven of 22 patients achieved independent sitting (mean, 8.2 months post-treatment); 19/20 patients ≥10.5 months of age or who discontinued the study prior to 10.5 months were surviving without permanent ventilation. The discontinued patient met the ventilatory support endpoint by clinical report, but this was not verified by download of ventilator usage from the BiPAP machine. Conclusions Preliminary data from STR1VE parallel the phase 1/2a study findings and may be associated with future survival, as well as pulmonary and bulbar function improvements.