June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Phase I/IIa Visual Acuity Outcomes 1.5-Years Post-Treatment with rAAV2/2-ND4, an Investigational Gene Therapy for ND4 LHON
Author Affiliations & Notes
  • Scott Uretsky
    Clinical, GenSight Biologics, Paris, France
  • Nitza Thomasson
    Clinical, GenSight Biologics, Paris, France
  • Celine BOUQUET
    Clinical, GenSight Biologics, Paris, France
  • Anne Galy
    Clinical, GenSight Biologics, Paris, France
  • Jean Philppe Combal
    Clinical, GenSight Biologics, Paris, France
  • Serge Fitoussi
    Clinical, GenSight Biologics, Paris, France
  • Jose Alain Sahel
    UPMC Univ Paris 06, INSERM U968, CNRS UMR 7210, Sorbonne Universités, Paris, France
    Institut de la Vision, Paris , France
  • Catherine Vignal
    Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris , France
    Foundation Rothschild , Paris , France
  • Footnotes
    Commercial Relationships   Scott Uretsky, GenSight Biologics (E); Nitza Thomasson, GenSight Biologics (E); Celine BOUQUET, GenSight Biologics (E); Anne Galy , GenSight Biologics (E); Jean Philppe Combal, GenSight Biologics (E); Serge Fitoussi , GenSight Biologics (E); 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), GenSight Biologics (F), LabEx (F), LIFESENSES (ANR-10-LABX-65) (F), Pixium Vision (C), Pixium Vision (I); Catherine Vignal, GenSight Biologics (C)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4681. doi:
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      Scott Uretsky, Nitza Thomasson, Celine BOUQUET, Anne Galy, Jean Philppe Combal, Serge Fitoussi, Jose Alain Sahel, Catherine Vignal; Phase I/IIa Visual Acuity Outcomes 1.5-Years Post-Treatment with rAAV2/2-ND4, an Investigational Gene Therapy for ND4 LHON. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4681.

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

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Abstract

Purpose : rAAV2/2-ND4 is an experimental gene therapy enabling allotopic transgene expression. We report visual acuity (VA) outcomes 1.5-years post-treatment in a Phase I/IIa (NCT02064569) open-label, dose-escalation safety study.

Methods : LHON patients with G11778A-ND4 mutation with stable vision loss received a single intravitreal injection of rAAV2/2-ND4 in their worst-seeing eye. Three patients were included in each dose-escalation cohort (9x109, 3x1010, 9x1010, 1.8x1011 vg/eye) and the extension cohort (9x1010 vg/eye) for a total of 15 patients. Post-hoc analysis of patient groups with ≤2-years vs. >2-years of vision loss at treatment and excluding the worst baseline VA (LogMAR>2.79) was performed.

Results : At baseline (N=15) mean/median (range) LogMAR in treated-worst and untreated-best eyes was 2.29/2.79 (1.10-3.01) and 2.03/2.01 (1.00-3.18) respectively; the difference between means is 0.265 (p=0.0342). Mean (range) vision loss duration was 72.3 months (8-271; median 22). All patients completed 48-week follow-up; one patient withdrew consent and 14 patients have completed 1.5-year follow-up. Mean LogMAR changes from baseline to 1.5-years post-treatment are as follows: For all patients (N=14): treated-worst eyes -0.612 vs. untreated-best eyes -0.308; mean difference -0.304. Excluding patients with baseline LogMAR>2.79: group with ≤2-years vision loss (N=5) treated-worst eyes -0.632 vs. untreated-best eyes -0.234; mean difference -0.398. In comparison, for this group, mean differences at weeks 24, 36 and 48 were: +0.136, -0.218, -0.338. In the >2-year vision loss group (N=6) treated-worst eyes -0.451 vs. untreated-best eyes +0.071; mean difference -0.523 with VA change of 3/6 patients driving results.

Conclusions : Mean LogMAR change at 1.5-years improved in treated-worst and untreated-best eyes; there is a sustainable, clinically relevant, greater improvement of ≥0.3LogMAR in treated-worst versus untreated-best eyes. For patients with ≤2-years vision loss, mean differences favoring treated-worst eyes are noted at 36-weeks and increase in magnitude at subsequent follow-up. Those affected >2-years show a clinically relevant (≥0.3LogMAR) mean difference for the first time at 1.5-years post-treatment.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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