Impact of age and motor function in a phase 1/2A study of infants with SMA type 1 receiving single-dose gene replacement therapy

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by progressive degeneration of lower motor neurons in the spinal cord, resulting in skeletal muscle atrophy and muscle weakness.

This study characterizes motor function responses after early dosing of AVXS-101 (onasemnogene abeparvovec) in gene replacement therapy in infants with severe spinal muscular atrophy type 1 (SMA1).

This study is a follow-up analysis of 12 infants with SMA1 who received the proposed therapeutic dose of AVXS-101 in a Phase 1 open-label study (NCT02122952). Infants were grouped according to age at dosing and baseline Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores: early dosing/low motor, dosed age less than three months with scores <20 (n = 3), late dosing, dosed at age three months or greater (n = 6), and early dosing/high motor, dosed age less than three months with scores ≥20 (n = 3).

The rapid, significant motor improvements among infants with severe SMA1 treated with AVXS-101 at an early age highlight the importance of newborn screening and early treatment and demonstrate the therapeutic potential of AVXS-101 regardless of baseline motor function.


Impact of Age and Motor Function in a Phase 1/2A Study of Infants With SMA Type 1 Receiving Single-Dose Gene Replacement Therapy. Lowes LP, Alfano LN, Arnold WD, Shell R, Prior TW, McColly M, Lehman KJ, Church K, Sproule DM, Nagendran S, Menier M, Feltner DE, Wells C, Kissel JT, Al-Zaidy S, Mendell J. Pediatr Neurol. 2019 May 13. pii: S0887-8994(19)30280-2. doi: 10.1016/j.pediatrneurol.2019.05.005. [Epub ahead of print]