SMA – THERAPY: P.261 Long-term follow-up of onasemnogene abeparvovec gene therapy in spinal muscular atrophy type 1 (SMA1)

Abstract

Onasemnogene abeparvovec (formerly AVXS-101) is designed to address the genetic root cause of SMA1. In the phase 1 trial (START; NCT02122952), patients who received a one time high-dose (proposed therapeutic dose) infusion (n=12) demonstrated significantly improved outcomes versus untreated natural history. START patients could electively enrol into long-term follow-up (LTFU; NCT03421977). Primary objective: long-term safety. Patients have annual visits (5 years) followed by annual phone contact (additional 10 years). Assessments include medical history/record review, physical examination, clinical laboratory evaluation, pulmonary assessments, and milestone maintenance. As of 31 Dec 2019, 13 patients (low dose, n=3; therapeutic dose, n=10) were enrolled. The oldest patients were aged 6.2 (low dose) and 5.6 (therapeutic dose) years. Serious adverse events (AEs) were reported in 8/13 patients; no new treatment-related AEs have emerged, supporting a favorable risk:benefit profile. All patients who received the therapeutic dose have survived and are free of permanent ventilation (mean [range] age at last datacut: 4.8 [4.3–5.6] years; mean [range] time since dosing: 4.5 [4.1–5.2] years). These patients have either maintained all previously attained milestones or gained new milestones; 2 patients have newly achieved standing with assistance while not receiving concomitant survival motor neuron 2 protein (SMN2) upregulating therapy at any point. Of the 10 enrolled patients who received therapeutic dose, 6 did not require regular, daily respiratory support more than 4 years after dosing. Additionally, 6 have never received concomitant SMN2 upregulating therapy. Data suggest that onasemnogene abeparvovec shows a favorable risk:benefit profile, and continues to demonstrate efficacy with new milestone developments.