PRO2 THE VALUE OF ONASEMNOGENE ABEPARVOVEC GENE-REPLACEMENT THERAPY IN IMPROVING SURVIVAL AND MOTOR FUNCTION AND DECREASING VENTILATORY SUPPORT AND HOSPITALIZATION CONTRASTED TO NATURAL HISTORY FOR SPINAL MUSCULAR ATROPHY TYPE 1

Abstract

Spinal muscular atrophy type 1 (SMA1) is a progressive monogenic neurologic disease causing loss of motor muscle function and bulbar muscle function essential for normal breathing and swallowing. This cross-study comparison highlights the value of onasemnogene abeparvovec (formerly AVXS-101) on survival, motor milestone achievement, ventilatory support, and hospitalizations in SMA1 patients. SMA1 patients (two SMN2 copies) were treated with onasemnogene abeparvovec (CL-101; NCT02122952; Cohort 2; n=12). Event-free survival (EFS; composite endpoint of time to death/permanent ventilation), motor milestone achievement, ventilatory support, and hospitalization were assessed (CL-101, ≥20 months; two natural history studies [untreated patients, 14 months of age: PNCR, ≥50% completing 12 months follow-up, N=23, and NN101, N=16]; sham control group from ENDEAR [NCT02193074]). The proportion of patients achieving EFS at ≥14 months was 30% in PNCR and 50% in NN101, compared with 100% in onasemnogene abeparvovec-treated patients. No patient in either natural history study achieved motor milestones, while 92% of onasemnogene abeparvovec-treated patients sat unassisted, 17% stood with assistance, and 17% walked independently. The proportion of patients surviving but requiring permanent assisted ventilation was 57% in PNCR and 0% in onasemnogene abeparvovec-treated patients. The mean unadjusted annualized rate of hospitalizations (total hospitalizations/total number of subject-years followed) was 4.3 for sham control-treated patients in ENDEAR and 2.1 for onasemnogene abeparvovec-treated patients. A single dose of onasemnogene abeparvovec resulted in dramatic survival and motor milestone achievements with reduced healthcare utilization, which could decrease cost and alleviate patient, caregiver, and societal burden, suggesting an overall improved quality of life compared to natural history.