July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Three-year update for the phase 3 voretigene neparvovec study in biallelic RPE65 mutation–associated inherited retinal disease
Author Affiliations & Notes
  • Stephen R Russell
    Ophthalmology, Univ of Iowa Hospitals & Clinics, Iowa City, Iowa, United States
    Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States
  • Jean Bennett
    Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
    Children's Hospital of Philadelphia, Pennsylvania, Pennsylvania, United States
  • Jennifer Wellman
    Spark Therapeutics, Philadelphia, Pennsylvania, United States
  • Daniel C Chung
    Spark Therapeutics, Philadelphia, Pennsylvania, United States
  • Katherine High
    Spark Therapeutics, Philadelphia, Pennsylvania, United States
  • Zi-Fan Yu
    Statistics Collaborative, Inc., Washington, District of Columbia, United States
  • Amy Tillman
    Statistics Collaborative, Inc., Washington, District of Columbia, United States
  • Albert M Maguire
    Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
    Children's Hospital of Philadelphia, Pennsylvania, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Stephen Russell, Spark Therapeutics (F), Spark Therapeutics (C); Jean Bennett, Spark Therapeutics (F), Spark Therapeutics (C); Jennifer Wellman, Spark Therapeutics (I), Spark Therapeutics (E); Daniel Chung, Spark Therapeutics (E), Spark Therapeutics (I); Katherine High, Spark Therapeutics (E), Spark Therapeutics (I); Zi-Fan Yu, Spark Therapeutics (C); Amy Tillman, Spark Therapeutics (C); Albert Maguire, Spark Therapeutics (F), Spark Therapeutics (C)
  • Footnotes
    Support  Spark Therapeutics
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3900. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Stephen R Russell, Jean Bennett, Jennifer Wellman, Daniel C Chung, Katherine High, Zi-Fan Yu, Amy Tillman, Albert M Maguire; Three-year update for the phase 3 voretigene neparvovec study in biallelic RPE65 mutation–associated inherited retinal disease. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3900.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : To present data from a phase 3 trial conducted in subjects with biallelic RPE65-mutation–associated inherited retinal disease (IRD) to determine whether improvements observed in functional vision, light sensitivity, and visual field 1 and 2 years after administration of voretigene neparvovec (VN) are maintained at 3 years after administration.

Methods : Twenty-nine subjects with biallelic RPE65 mutation–associated IRD were randomized to either intervention (I; bilateral subretinal VN within 90 days of baseline) or control/intervention (C; VN after 1 year of observation). The primary endpoint was bilateral multi-luminance mobility test (MLMT) at 7 standardized illumination levels. Secondary endpoints included full-field light sensitivity threshold (FST) testing, visual acuity (VA), and Goldmann kinetic visual field (GVF).

Results : MLMT mean (SD) bilateral change score was 1.8 levels (1.0) for I subjects (n=20) at 3 years and 2.1 levels (1.6) for C subjects (n=9) at 2 years, with >70% of all subjects able to pass MLMT at the lowest light level measured at 3 years (I subjects) and 2 years (C subjects). Mean change in white light FST averaged over both eyes was -2.04 log10 (cd.s/m2) (1.43) at 3 years for I subjects (n=19) and -2.69 log10 (cd.s/m2) (1.41) at 2 years for C subjects (n=9). Improvements in FST were >150-fold in light sensitivity for all subjects measured at 3 years (I subjects) and 2 years (C subjects). Mean change (SD) in VA averaged over both eyes was consistent through 3 years for I subjects and 2 years for C subjects. The mean change (SD) in sum total degrees on GVF III4e, averaged over both eyes, was 282 (257) for I subjects at 3 years and 183 (310) in C subjects at 2 years. The safety profile is consistent with vitrectomy and the subretinal injection procedure, and no deleterious immune responses occurred.

Conclusions : Gene augmentation by VN therapy demonstrated a favorable benefit-risk profile with improved functional vision and visual function in subjects with biallelic RPE65 mutation–associated IRD for at least 3 years following administration in the I group. Improvements in MLMT, FST, and GVF in C subjects were consistent with those observed in I subjects. The safety profile is consistent with the administration procedure.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×