July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Subanalysis of data from rAAV.sFLT-1 phase 1 and 2a randomized gene therapy trials for wet age-related macular degeneration.
Author Affiliations & Notes
  • Elizabeth Rakoczy
    Centre of Ophthalmology and Visual Science, The University of Western Australia, Nedlands, Western Australia, Australia
    Molecular Ophthalmology, Lions Eye Institute, Nedlands, Western Australia, Australia
  • Aaron Magno
    Molecular Ophthalmology, Lions Eye Institute, Nedlands, Western Australia, Australia
  • Chooi-May Lai
    Centre of Ophthalmology and Visual Science, The University of Western Australia, Nedlands, Western Australia, Australia
  • Mariapia Degli-Esposti
    Centre of Ophthalmology and Visual Science, The University of Western Australia, Nedlands, Western Australia, Australia
  • Ian Constable
    Centre of Ophthalmology and Visual Science, The University of Western Australia, Nedlands, Western Australia, Australia
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1448. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Elizabeth Rakoczy, Aaron Magno, Chooi-May Lai, Mariapia Degli-Esposti, Ian Constable; Subanalysis of data from rAAV.sFLT-1 phase 1 and 2a randomized gene therapy trials for wet age-related macular degeneration.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1448.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : To provide the three year follow-up patient focused data analysis of Phase 1 and 2a clinical trials of high dose rAAV.sFLT-1 gene therapy (GT) for wet age-related macular degeneration (wAMD).

Methods : Thirty-seven patients with advanced wAMD were randomized in a 2:1 ratio (GT:control). All patients received intravitreal ranibizumab at baseline and at Day 28. GT patients received rAAV.sFLT-1, 1x1011 vg subretinally at Day 7. All patients were assessed monthly for 12 months, at 18 and 36 months to pre-specified criteria and received retreatment anti-VEGF injections pro re nata.

Results : All procedure-related adverse events were self-resolved by 12 months and there were no GT-related adverse events reported after. Control patients received a median of 7.0 anti-VEGF retreatments and lost a median of 7.0 early treatment diabetic retinopathy study (ETDRS) letters. A previously described, a subgroup of GT patients (HD-1) received a median of 2.5 retreatments over 36 months and lost a median of 4.0 ETDRS letters. The other subgroup of GT patients (HD-2), received 11.0 retreatments over 36 months, and lost a median of 7.0 ETDRS letters. Centre point thickness fluctuated over the 36 months and did not correlate with BCVA changes. At 36 months, 33% of control, and 51% of HD-1 patients showed maintenance/improvement of visual acuity. Only HD-1 patients maintained significant visual improvement at 36 months. Geographic atrophy development was significantly lower in the HD-1 than in control patients.

Conclusions : Conclusions: These results demonstrated that GT was safe and that rAAV.sFLT-1 GT is bioequivalent to traditional anti-VEGF treatments. Those GT patients who responded at year one continued to do well and the presence of neutralising antibodies at base line did not seem to affect outcome. Over the long-term only GT patients maintained meaningful visual improvement, and had a lower tendency of developing geographic atrophy. We propose that increasing the dose of rAAV.sFLT-1 and the selection of treatment naïve patients might further increase the efficacy of GT.

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.

×