TY - JOUR
T1 - Voretigene neparvovec-rzyl for treatment of RPE65-mediated inherited retinal diseases
T2 - a model for ocular gene therapy development
AU - Ciulla, Thomas A.
AU - Hussain, Rehan M.
AU - Berrocal, Audina M.
AU - Nagiel, Aaron
N1 - Publisher Copyright:
© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2020/6/2
Y1 - 2020/6/2
N2 - 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.
AB - 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.
KW - Gene therapy
KW - Leber’s congenital amaurosis
KW - RPE65
KW - adeno-associated virus
KW - inherited retinal disease
KW - luxturna
KW - retinitis pigmentosa
KW - voretigene neparvovec-rzyl
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U2 - 10.1080/14712598.2020.1740676
DO - 10.1080/14712598.2020.1740676
M3 - Article
C2 - 32149547
AN - SCOPUS:85082443196
VL - 20
SP - 565
EP - 578
JO - Expert Opinion on Biological Therapy
JF - Expert Opinion on Biological Therapy
SN - 1471-2598
IS - 6
ER -