June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Preliminary Results from a First-in-human Phase I/II Gene Therapy Study (FOCUS) of Subretinally Delivered GT005, an Investigational AAV2 Vector, in Patients with Geographic Atrophy Secondary to Age-related Macular Degeneration
Author Affiliations & Notes
  • Jared Nielsen
    Wolfe Eye Clinic PC, West Des Moines, Iowa, United States
  • Robert E MacLaren
    Oxford University Hospitals NHS Foundation Trust, Oxford, Oxfordshire, United Kingdom
  • Jeffrey S Heier
    OCB, Boston, Massachusetts, United States
  • David Steel
    Sunderland Eye Infirmary, Sunderland, Tyne and Wear, United Kingdom
  • Tsveta Ivanova
    Manchester University NHS Foundation Trust, Manchester, Greater Manchester, United Kingdom
  • Sobha Sivaprasad
    Moorfields Eye Hospital NHS Foundation Trust, London, London, United Kingdom
  • Paulo Stanga
    The Retina Clinic London, London, United Kingdom
  • Clare Bailey
    Bristol Eye Hospital, Bristol, Bristol, United Kingdom
  • Peter Charbel Issa
    Oxford University Hospitals NHS Foundation Trust, Oxford, Oxfordshire, United Kingdom
  • Luisa Mendonca
    Gyroscope Therapeutics, United Kingdom
  • James Francis
    Gyroscope Therapeutics, United Kingdom
  • Darin Curtiss
    Gyroscope Therapeutics, United Kingdom
  • Jane Hughes
    Gyroscope Therapeutics, United Kingdom
  • Nadia K Waheed
    Gyroscope Therapeutics, United Kingdom
  • Footnotes
    Commercial Relationships   Jared Nielsen Genentech, Regeneron, Iveric Bio, Novartis, Kodiak Scientific, Code C (Consultant/Contractor), Kodiak Scientific, Genentech/Roche, Iveric Bio, Regeneron, Gyroscope Therapeutics, Novartis, GrayBug, Gemini, Ophtea, Aerpio, Alimera, Alcon, Digital Diagnostics, Novo Nordisk, Code F (Financial Support); Robert MacLaren Gyroscope Therapeutics, Code C (Consultant/Contractor), Gyroscope Therapeutics, Code F (Financial Support); Jeffrey Heier Gyroscope Therapeutics, Code C (Consultant/Contractor); David Steel Gyroscope Therapeutics, Roche, BVI, Alcon, Code C (Consultant/Contractor), Gyroscope Therapeutics, Alcon, Bayer, DORC, Boehringer , Code F (Financial Support); Tsveta Ivanova None; Sobha Sivaprasad Bayer, Novartis, Allergan, Roche, Boehringer Ingelheim, Optos, Oxurion, Oculis, Biogen, Apellis, Heidelberg Engineering, Code F (Financial Support); Paulo Stanga None; Clare Bailey Bayer, Novartis, Roche, Jansen, Boehringer Ingelheim, Alimera sciences, Code C (Consultant/Contractor); Peter Charbel Issa None; Luisa Mendonca Gyroscope Therapeutics, Code C (Consultant/Contractor); James Francis Gyroscope Therapeutics, Code E (Employment); Darin Curtiss Gyroscope Therapeutics, Code E (Employment); Jane Hughes Gyroscope Therapeutics, Code E (Employment); Nadia Waheed Nidek Medical Products, Boehringer Ingelheim, Topcon, Code C (Consultant/Contractor), Gyroscope Therapeutics, Code E (Employment), Carl Zeiss Meditec, Heidelberg, Nidek Medical Products, Topcon, Code F (Financial Support), Gyroscope Therapeutics, Ocudyne, Code I (Personal Financial Interest)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1504. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Jared Nielsen, Robert E MacLaren, Jeffrey S Heier, David Steel, Tsveta Ivanova, Sobha Sivaprasad, Paulo Stanga, Clare Bailey, Peter Charbel Issa, Luisa Mendonca, James Francis, Darin Curtiss, Jane Hughes, Nadia K Waheed; Preliminary Results from a First-in-human Phase I/II Gene Therapy Study (FOCUS) of Subretinally Delivered GT005, an Investigational AAV2 Vector, in Patients with Geographic Atrophy Secondary to Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1504.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : To investigate safety and dose response of subretinally delivered GT005, an investigational recombinant adeno-associated viral (AAV2) vector encoding Complement Factor I (CFI), for treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Methods : FOCUS (NCT03846193) is an open-label multicenter study consisting of 4 parts: dose-escalation of GT005 delivered via transvitreal subretinal injection (TVSI), dose-expansion with TVSI, dose-escalation of GT005 delivered using the Orbit subretinal delivery system (Orbit SDS), dose-expansion with the Orbit SDS. All patients had bilateral GA at baseline and received a single subretinal administration of GT005 in the study eye. Primary endpoint is safety of GT005 over 48 weeks, with secondary endpoints including anatomical/functional outcomes and changes in complement protein expression in the vitreous humor. Part 1 explored 3 GT005 dose levels (2E10, 5E10 and 2E11 vector genomes [vg]) delivered via TVSI, Part 2 further explored dose-levels that were shown to be safe and tolerable in Part 1. Interim data from the TVSI cohorts are presented herein

Results : On December 2021, enrolment was complete for Parts 1 and 2 and 31 patients had received GT005 via TVSI, 11 in Part 1 and 20 in Part 2, with a mean follow-up of 51.8 weeks (range: 2.3 to 144.3). At baseline, the mean age was 80.3 years (68 to 93), 71.0% (22/31) were women, and 96.8% (30/31) were white. All 3 dose levels of GT005 delivered via TVSI were well-tolerated, with no dose-related trends in the frequency and type of reported adverse events (AEs) to date. Of the 48 treatment-emergent ocular AEs in 21 patients, 29 occurred in the study eye only and 10 were bilateral. From the AEs affecting the study eye, majority were mild (30/39) and considered unrelated to GT005 (37/39). From the moderate AEs affecting the study eye (9/39), 5 were related to worsening of cataracts, and 1 described the conversion to choroidal neovascularization. No severe or serious ocular AEs were reported. There were no signs of GT005-related inflammation. Biomarker analysis of vitreous including complement factors at baseline and follow-up will be presented.

Conclusions : GT005 had a positive safety profile at 2E10 to 2E11vg with no signs of GT005-related inflammation.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

×
×

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.

×