Impact of Age and Motor Function in a Phase 1/2A Study of Infants With SMA Type 1 Receiving Single-Dose Gene Replacement Therapy

Pediatr Neurol. 2019 Sep;98:39-45. doi: 10.1016/j.pediatrneurol.2019.05.005. Epub 2019 May 13.


Background: 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).

Methods: 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: (1) early dosing/low motor, dosed age less than three months with scores <20 (n = 3), (2) late dosing, dosed at age three months or greater (n = 6), and (3) early dosing/high motor, dosed age less than three months with scores ≥20 (n = 3).

Results: Early dosing/low motor group demonstrated a mean gain of 35.0 points from a mean baseline of 15.7, whereas the late dosing group had a mean gain of 23.3 from a mean baseline of 26.5. The early dosing/high motor group quickly reached a mean score of 60.3, near the scale maximum (64), from a mean baseline of 44.0. Despite a lower baseline motor score, the early dosing/low motor group achieved sitting unassisted earlier than the late dosing group (mean age: 17.0 vs 22.0 months). The early dosing/high motor group reached this milestone earliest (mean age: 9.4 months).

Conclusions: 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.

Keywords: AVXS-101; CHOP-INTEND; Gene replacement therapy; Onasemnogene abeparvovec; Spinal muscular atrophy.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Dependovirus
  • Female
  • Follow-Up Studies
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • Infant
  • Male
  • Motor Disorders / etiology
  • Motor Disorders / therapy*
  • Outcome Assessment, Health Care*
  • SMN Complex Proteins / therapeutic use*
  • Severity of Illness Index
  • Spinal Muscular Atrophies of Childhood / complications
  • Spinal Muscular Atrophies of Childhood / therapy*


  • SMN Complex Proteins

Associated data