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

: 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 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.: VN serves as a model for ocular gene therapy development, while 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 mutation-associated IRD, which predominantly impairs rod function. Additionally, the dosage, administration technique, pharmacokinetics, and safety data of VN are reviewed.: 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.