Onasemnogene abeparvovec gene therapy for spinal muscular atrophy type 1: phase 3 study update (str1ve-eu)

Onasemnogene abeparvovec (formerly AVXS-101), a one-time intravenous AAV9-based gene therapy, addresses the genetic root cause of spinal muscular atrophy type 1 (SMA1). We report preliminary data from the phase 3 STR1VE-EU (2017-000266-29/ NCT03461289 ) study evaluating efficacy and safety of onasemnogene abeparvovec infusion. STR1VE-EU is an ongoing, multicenter, open-label, single-arm, single-dose study in SMA1 patients aged <6 months (biallelicSMN1mutations, 1–2xSMN2). Outcomes: independent sitting ≥10 seconds throughout 18 months; survival (no death/permanent ventilation) at 14 months. Enrollment is complete (31 May 2019; N=33, all 2xSMN2). Mean age at dosing: 4.1 (1.4–6) months. Mean baseline CHOP INTEND score: 28 (14–55). Mean time in study: 4.8 (0.4–9.2) months. At baseline, 9/33 (27%) patients required nutritional support and 7/33 (17%) required ventilatory support. Relative to baseline, mean CHOP INTEND score increased 6.4,10.6, and 12.3 points at 1, 3, and 5 months post-dosing, respectively. Overall, 32 patients were surviving without permanent ventilation, including 9/10 patients who reached 10.5 months of age or experienced an event. One patient died (age 6.8 months, hypoxic- ischemic brain injury secondary to respiratory tract infection due to SMA1). Interim data from the ongoing STR1VE-EU study shows that onasemnogene abeparvovec has therapeutic benefit in patients with SMA1. 1ik4ausar078@avexis.com