Onasemnogene Abeparvovec-xioi: Gene Therapy for Spinal Muscular Atrophy

Ann Pharmacother. 2020 Oct;54(10):1001-1009. doi: 10.1177/1060028020914274. Epub 2020 Mar 23.

Abstract

Objective: To review the efficacy and safety of onasemnogene abeparvovec-xioi (Zolgensma) in the treatment of spinal muscular atrophy (SMA).

Data sources: An English-language literature search of PubMed, MEDLINE, and Ovid (1946 to December 2019) was completed using the terms onasemnogene, AVXS-101, and spinal muscular atrophy. Manufacturer prescribing information, article bibliographies, and data from ClinicalTrials.gov were incorporated in the reviewed data.

Study selection/data extraction: All studies registered on ClinicalTrials.gov were incorporated in the reviewed data.

Data synthesis: Onasemnogene is the first agent for SMA utilizing gene therapy to directly provide survival motor neuron 1 (SMN1) gene to produce SMN protein. Four publications of 1 clinical trial, 1 comparison study of treatment effects, and 1 combination therapy case series have been published.

Relevance to patient care and clinical practice: Onasemnogene is a one time dose approved by the Food and Drug Administration for SMA patients <2 years old who possess mutations in both copies of the SMN1 gene.

Conclusion: Onasemnogene appears to be an efficacious therapy for younger pediatric patients with SMA type 1. Concerns include drug cost and potential liver toxicity. Long-term benefits and risks have not been determined.

Keywords: AVXS-101; Zolgensma; onasemnogene; spinal muscular atrophy.

Publication types

  • Review

MeSH terms

  • Biological Products / therapeutic use*
  • Child, Preschool
  • Drug Approval
  • Female
  • Genetic Therapy / methods*
  • Humans
  • Mutation
  • Recombinant Fusion Proteins / therapeutic use*
  • Spinal Muscular Atrophies of Childhood / genetics
  • Spinal Muscular Atrophies of Childhood / therapy*
  • Survival of Motor Neuron 1 Protein / biosynthesis
  • Survival of Motor Neuron 1 Protein / genetics*
  • United States
  • United States Food and Drug Administration

Substances

  • Biological Products
  • Recombinant Fusion Proteins
  • Survival of Motor Neuron 1 Protein
  • Zolgensma