July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Visual Acuity and Safety Outcomes 2.5 Years Post-Treatment with rAAV2/2-ND4, an Investigational Gene Therapy for ND4 LHON: Results of a Phase I/II Trial
Author Affiliations & Notes
  • Jose A. Sahel
    UMR-S 968, Institut de la Vision, Paris, France
    Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Barrett Katz
    GenSight Biologics , New Yorik, New York, United States
  • Catherine Vignal-Clermont
    Fondation Ophtalmologique Adolphe de Rothschild, Paris, France
  • Laure Blouin
    GenSight Biologics , New Yorik, New York, United States
  • Footnotes
    Commercial Relationships   Jose Sahel, Banque publique d'Investissement (F), Chronocam (I), Chronolife (I), ERC Synergy "HELMHOLTZ" (F), Foundation Fighting Blindness (F), Genesignal (C), GenSight Biologics (C), GenSight Biologics (I), LabEx LIFESENSES (ANR-10-LABX-65) (F), Pixium Vision (C), Pixium Vision (I), Tilak Healthcare (I); Barrett Katz, GenSight Biologics (E); Catherine Vignal-Clermont, GenSight Biologics (C); Laure Blouin, GenSight Biologics (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4530. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Jose A. Sahel, Barrett Katz, Catherine Vignal-Clermont, Laure Blouin; Visual Acuity and Safety Outcomes 2.5 Years Post-Treatment with rAAV2/2-ND4, an Investigational Gene Therapy for ND4 LHON: Results of a Phase I/II Trial. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4530.

      Download citation file:

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

  • Supplements

Purpose : rAAV2/2-ND4 is an investigational gene therapy enabling allotopic transgene expression. We report visual acuity and safety outcomes 2.5 years post-treatment in a Phase I/II open-label, dose-escalation trial.

Methods : Fifteen LHON subjects with G11778A ND4 mutation received a single intravitreal injection of rAAV2/2-ND4 in their worse seeing eye. Three subjects were included in each dose-escalation cohort (9x109, 3x1010, 9x1010, 1.8x1011 vg/eye) and 3 in an extension cohort (9x1010 vg/eye).

Results : At study entry, mean LogMAR visual acuity in treated eyes was 2.29. Mean of duration of vision loss in treated eyes was 72.3 months.
In subjects with ≤ 2-years vision loss and LogMAR visual acuity <2.79 at baseline (N=5), mean LogMAR acuity changes from baseline to Year 2.5 were: -0.550 in treated eyes vs. -0.250 in untreated eyes. Mean differences in LogMAR acuities in treated vs. untreated eyes, from baseline to Weeks 24, 36, 48, 78, 96, and Year 2.5 were respectively: +0.136, -0.218, -0.338, -0.398, -0.278, -0.300. Three out of 5 of treated eyes (60%) gained ≥15 ETDRS letters by Year 2.5.
No unexpected adverse events (AE) were noted. No systemic AE or any serious AE were related to study drug or procedures. Most frequently reported ocular AEs included anterior and intermediate uveitis and transient IOP elevation, mostly mild and all responsive to treatment.

Conclusions : At 2.5 years, in subjects with ≤ 2 years vision loss, 60% of treated eyes had a clinically meaningful gain in vision (≥15 ETDRS letters). In those subjects, better acuity was seen in treated vs. untreated eyes beginning after Week 36. Intravitreal rAAV2/2-ND4 was safe and well-tolerated. Recent reports of successful gene therapy in adrenoleukodystrophy and hematologic malignancy suggest that subjects treated earlier in the course of their disease demonstrate better clinical outcomes. Our results too suggest that subjects treated sooner following their conversion and with relatively preserved central acuity demonstrate better gains in vision.

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.