Long-Term Follow-Up of Onasemnogene Abeparvovec Gene Therapy in Patients with Spinal Muscular Atrophy Type 1


Clinical Trials

Poster Number: 98


Jerry Mendell, Center for Gene Therapy, Nationwide Children’s Hospital, Melissa Wigderson, Novartis Gene Therapies, Inc., Iulian Alecu, Novartis Pharmaceuticals, Lina Yang, Novartis Pharmaceuticals, Lesa Mehl, Novartis Institutes for BioMedical Research, Anne Connolly, MD, Nationwidechildren's Hospital

Background: In the Phase I trial (START; NCT02122952), spinal muscular atrophy type 1 (SMA1) patients who received the proposed therapeutic dose of onasemnogene abeparvovec (n=12) demonstrated substantially improved outcomes versus natural history. _x000D_
Objective: Evaluate long-term safety and efficacy of onasemnogene abeparvovec in patients with SMA1 (biallelic SMN1 mutations/deletions and two SMN2 copies) who enrolled into the LT-001 study (NCT03421977)._x000D_
Methods: The primary objective was to evaluate long-term safety assessed by medical history/record review, physical examination, laboratory evaluation, and pulmonary assessments. Efficacy was evaluated by assessing developmental milestones. _x000D_
Results: As of May 23, 2022, 13 patients (low-dose, n=3; therapeutic dose, n=10) were enrolled and followed for a mean of 95.1 (low-dose) and 83.5 (therapeutic dose) months. The oldest patient was 8.5 years of age (8.0 years post-dosing). In five patients, respiratory events and dehydration were reported. No deaths, serious treatment-emergent adverse events related to treatment, or any late-onset treatment events were reported. All patients who received the therapeutic dose survived, were free of permanent ventilation (mean [range] age at last data cut, 7.1 [6.6–7.9] years), and have maintained achieved developmental milestones. Three have achieved a new developmental milestone of standing with assistance (two without add-on therapy and one with nusinersen add-on). One patient in the low-dose cohort also achieved new developmental milestones (head control, sitting with support). Only three of 10 patients receiving the therapeutic dose required respiratory support, a decrease from five of 10 in December 2019. Four of 10 patients did not require any non-mechanical feeding support; all 10 fed orally. Four of 10 patients receiving the therapeutic dose never received add-on therapy. Of the six remaining, two started risdiplam, three switched from nusinersen to risdiplam, and one discontinued nusinersen. _x000D_
Conclusions: Onasemnogene abeparvovec continues to demonstrate a favorable risk-benefit profile and durable efficacy up to 8 years post-dosing.