In the Phase I trial (START; NCT02122952), SMA type 1 patients who received a one-time high-dose (proposed therapeutic dose) infusion (n=12) demonstrated significantly improved outcomes versus untreated natural history. Patients from five intravenous and intrathecal studies may enroll in LT-002.

Evaluate long-term safety/efficacy of patients previously treated in the onasemnogene abeparvovec (formally AVXS-101) clinical development program who electively enrolled into LTFU studies LT-001 (NCT03421977) and LT-002 (NCT04042025).

Primary objective: long-term safety. Patients have annual visits (five years) followed by annual phone contact (ten years). Assessments include medical history/record review, physical examination, laboratory evaluation, pulmonary assessments, and milestone maintenance. LT-002 is an additional LTFU study with 308 participants planned from other onasemnogene abeparvovec clinical trials. Enrollment is ongoing.

As of 11 June 2020, 13 patients (low dose, n=3; therapeutic dose, n=10) were enrolled in LT-001. The oldest patients were aged 6.7 (low dose) and 6.1 (therapeutic dose) years. Serious adverse events were reported in 8/13 patients; however, none were considered related to treatment or led to study discontinuation. All patients who received the therapeutic dose have survived and are free of permanent ventilation (mean [range] age at last datacut: 5.2 [4.7–6.1] years; mean [range] time since dosing: 5.2 [4.6–6.2] years). These patients have either maintained all previously attained milestones or gained new milestones; two have newly achieved standing with assistance while not receiving concomitant nusinersen at any point. Of the ten enrolled patients who received the therapeutic dose, six did not require regular, daily respiratory support more than four years after dosing. Nusinersen treatment was ongoing in seven of 13 patients. As of 11 June 2020, six patients were enrolled in LT-002 with minimal follow-up.

Data suggest that onasemnogene abeparvovec shows a favorable risk:benefit profile, and continues to demonstrate durable efficacy.