Voretigene neparvovec-rzyl for treatment of RPE65-mediated inherited retinal diseases: a model for ocular gene therapy development

Thomas A. Ciulla, Rehan M. Hussain, Audina M. Berrocal, Aaron Nagiel

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Introduction: Over a decade of research and development culminated in the 2017 United States (US) Food and Drug Administration (FDA) approval of voretigene neparvovec-rzyl (VN) for RPE65 mutation-associated inherited retinal disease (IRD), the first approved gene therapy for a hereditary genetic disease in the US, and the first and only pharmacologic treatment for an IRD. Areas covered: VN serves as a model for ocular gene therapy development, while RPE65 mutation-associated IRD serves as an example of a well-suited candidate disorder. This review also discusses development considerations for viral vector gene augmentation, and, studies that led to VN’s FDA approval. Subretinal injection of VN resulted in improved performance on the novel multi-luminance mobility test (MLMT), light sensitivity, and visual fields in patients with RPE65 mutation-associated IRD, which predominantly impairs rod function. Additionally, the dosage, administration technique, pharmacokinetics, and safety data of VN are reviewed. Expert Opinion: As a model for development, special challenges associated with the introduction of this first ocular gene therapy include limited genetic testing in clinical practice, novel surgical complexity of ocular gene therapy administration, new functional vision endpoints, as well as unique development, launch, and reimbursement considerations associated with orphan therapies and one-time gene therapies.

Original languageEnglish (US)
Pages (from-to)565-578
Number of pages14
JournalExpert Opinion on Biological Therapy
Issue number6
StatePublished - Jun 2 2020


  • Gene therapy
  • Leber’s congenital amaurosis
  • RPE65
  • adeno-associated virus
  • inherited retinal disease
  • luxturna
  • retinitis pigmentosa
  • voretigene neparvovec-rzyl

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry


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