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.