TY - JOUR T1 - 250 AVXS-101 phase 3 study in spinal muscular atrophy type 1 JF - Journal of Neurology, Neurosurgery & Psychiatry JO - J Neurol Neurosurg Psychiatry SP - e60 LP - e60 DO - 10.1136/jnnp-2019-ABN-2.202 VL - 90 IS - 12 AU - John W Day AU - Claudia A Chiriboga AU - Thomas O Crawford AU - Basil T Darras AU - Richard S Finkel AU - Anne M Connolly AU - Susan T Iannaccone AU - Nancy L Kuntz AU - Loren DM Peña AU - Meredith Schultz AU - Perry B Shieh AU - Edward C Smith AU - Imran Kausar AU - Douglas E Feltner AU - Francis G Ogrinc AU - Haojun Ouyang AU - Thomas A Macek AU - Elaine Kernbauer AU - Lynlee M Muehring AU - James L’Italien AU - Douglas M Sproule AU - Brian K Kaspar AU - Jerry R Mendell Y1 - 2019/12/01 UR - http://jnnp.bmj.com/content/90/12/e60.2.abstract N2 - Background Onasemnogene abeparvovec (AVXS-101), a one-time intravenous gene-replacement therapy, treats the genetic root cause of spinal muscular atrophy (SMA). In the phase 1 study, AVXS-101 dramatically improved survival, motor function, and motor milestone achievement in SMA type 1 (SMA1) patients.Methods STR1VE is a phase 3, multicenter, open-label study (NCT03306277) in SMA1 patients <6 months (bi-allelic survival motor neuron 1 gene [SMN1] mutations/deletions, 2 SMN2 copies). Primary outcomes are independent sitting ≥30 seconds at 18 months of age, and survival (no death/permanent ventilation) at 14 months. Secondary outcomes include ability to thrive and ventilatory support at 18 months. Exploratory outcomes include CHOP-INTEND and Bayley-III.Results Enrollment is complete (22 patients dosed). Mean age at symptom onset, genetic diagnosis, and enrollment was 1.9 (0–4.0), 2.1 (0.5–4.0), and 3.7 (0.5–5.9) months. At baseline, no patient required ventilatory/nutritional support. Mean baseline CHOP-INTEND: 32.6 (17.0–52.0) points; increased by 6.9 (-4.0–16.0), 9.2 (0–18.0), and 11.7 (-3.0–23.0) points at 1, 2, and 3 months; independent sitting: 11/22 patients; survival at 13.6 months: 13/15 (87%) (8 March 2019 datacut).Conclusions Preliminary data from the AVXS-101 phase 3 study show rapid motor function improvements in SMA1 patients, paralleling phase 1 findings. ER -