Intravenous (IV) Onasemnogene Abeparvovec-xioi Clinical Development Programs in Spinal Muscular Atrophy (SMA) Type 1 (SMA1): Integrated Safety Report


Gene targeted therapies

Poster Number: 75


Deepa Chand, Richard Finkel, MD, Eugenio Mercuri, MD, Riccardo Masson, Julie Parsons, MD, Aaron Kleyn, Douglas M. Sproule, Douglas E. Feltner, Sitra Tauscher-Wisniewski, MD, Jerry R. Mendell


1. AveXis, Inc., 2. Nemours Children’s Hospital, University of Central Florida College of Medicine, 3. Department of Paediatric Neurology,Catholic University, Rome , 4. Carlo Besta Neurological Research Institute Foundation, Milan, Italy, 5. Children's Hospital of Colorado, University of Colorado School of Medicine, 6. AveXis, Inc., 7. AveXis, Inc., 8. AveXis, Inc., 9. AveXis, Inc., 10. Center for Gene Therapy, Nationwide Children’s Hospital

Background: SMA is a rapidly progressing neurologic disease. IV onasemnogene abeparvovec-xioi (formerly AVXS-101) gene therapy addresses the genetic root cause of SMA, survival motor neuron 1 gene (SMN1) deletion/mutation.
Objective: Assess safety of IV onasemnogene abeparvovec in SMA patients (pts) across 4 clinical trials.
Approach: Pts with symptomatic or pre-symptomatic SMA1 (2–3xSMN2) received a single IV onasemnogene abeparvovec dose. Investigators monitored and reported pt adverse events (AEs) in accordance with study protocols. Treatment-emergent AEs (incidence, severity) were assessed per CTCAE.
Results: As of 8 Mar 2019, 75 pts received IV onasemnogene abeparvovec (therapeutic dose [1.1e14 vg/kg]; mean [SD, range] age: 2.5 [1.8, 0.3–7.9] months [mos]; weight: 5.33 [1.33, 3.0–8.4] kg). As noted in the US package insert (PI), 2 deaths were reported: pt aged 7.8 mos, respiratory arrest 5.7 mos post-treatment (deemed unrelated to treatment); pt aged 6.8 mos, hypoxic/ischemic brain damage and an acute illness including respiratory infection, transaminase elevations, and transient platelet decrease.
Sixty-four (85%) pts reported ≥1 AE; 33 (44%) pts had treatment-related AEs; 29 (39%) pts had serious AEs (death, life-threatening, hospitalization, disability/permanent damage, other important medical event). Pyrexia was reported in 30 (40%) pts (9 pts ≤1 week after dosing); considered treatment-related in 4 (5%) pts. Eight (11%) pts experienced increased liver transaminases (>ULN); these were considered treatment-related AEs, were clinically asymptomatic, and generally resolved with prednisolone (exception: 2 pts described in PI). Transient thrombocytopenia was reported, without clinically significant bleeding/bruising. Anticipated safety update: Q1 2020.
Conclusions: As of 8 Mar 2019, the IV onasemnogene abeparvovec safety profile remains consistent with the PI and continues to be monitored in clinical trials/managed access programs/the post-marketing setting.