Abstract Details

Title Event-Free Survival and Motor Milestone Achievement Following AVXS-101 and Nusinersen Interventions Contrasted to Natural History for Type I Spinal Muscular Atrophy Patients

Topic Child Neurology and Developmental Neurology

Presentation(s) S25 - Child Neurology: Spinal Muscular Atrophy: Treatments and Outcomes (1:44 PM-1:55 PM)

Poster/Presentation
Number 005

Background SMA1 is a rapidly progressing, debilitating neurodegenerative disease resulting from bi-allelic survival motor neuron 1 (SMN1) gene deletion/mutation and subsequent motor neuron loss, muscle weakness, respiratory failure, and early death.

Objective

To describe the impact of onasemnogene abeparvovec (AVXS-101) on survival and motor milestone achievement in spinal muscular atrophy type 1 (SMA1) patients (CL-101 study) contrasted with response to nusinersen (ENDEAR study) and untreated patients in natural history studies.

Design/Methods

SMA1 patients (two SMN2 copies) were treated with AVXS-101 (CL-101; NCT02122952; cohort 2; N=12) or nusinersen (ENDEAR; NCT02193074; N=80). Event-free survival (EFS, composite endpoint of time to death or permanent ventilation), motor milestone achievement, and nutritional/ventilatory support (CL-101, ≥20 months; ENDEAR, ≥14 months of age) were contrasted with those from two comparable natural history studies (up to 14 months of age): Pediatric Neuromuscular Clinical Research network (PNCR; N=23) and NN101 (NCT01736553; N=16).

Results The proportion of patients achieving EFS at ≥14 months was 30% in PNCR, 50% in NN101, 66% in nusinersen-treated patients, and 100% in AVXS-101-treated patients. No patient in either natural history study achieved motor milestones. In nusinersen-treated patients, 8% sat independently and 1% stood; 92% of AVXS-101-treated patients sat unassisted, 17% stood with assistance, and 17% walked independently. Achievement of additional milestones in long-term follow-up demonstrated the durability of AVXS-101. Seventy percent of PNCR study patients received nutritional support. In contrast, 86% of AVXS-101-treated patients who were independent of nutritional support at baseline continued to eat exclusively by mouth, and 92% of all AVXS-101-treated patients achieved the ability to speak or had stable/improved swallowing function.

Conclusions

A single intravenous infusion of AVXS-101 in the CL-101 study resulted in unprecedented clinical outcomes, including improved survival, motor milestone achievement, and reduced ventilatory/nutritional support, relative to nusinersen in the ENDEAR study and in contrast to natural history cohorts.

Authors/Disclosures
Omar Dabbous PRESENTER	Omar Dabbous has received personal compensation for serving as an employee of Novartis Gene Therapies. Omar Dabbous has received stock or an ownership interest from Novartis Gene Therapies.
	No disclosure on file
Douglas Feltner	No disclosure on file
	No disclosure on file
	No disclosure on file
Marcus Droege	No disclosure on file
	No disclosure on file
Khan Farid	No disclosure on file
Ramesh Arjunji	No disclosure on file

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