September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Phase I Safety and Tolerability results for RetinoStat®, a Lentiviral Vector Expressing Endostatin and Angiostatin, in Patients with Advanced Neovascular Age-Related Macular Degeneration
Author Affiliations & Notes
  • Andreas K Lauer
    Ophthalmology, Casey Eye Institute - Oregon Health & Science University, Portland, Oregon, United States
  • Peter A Campochiaro
    Ophthalmology, Johns Hopkins University Hospital School of Medicine Wilmer Eye Institute , Baltimore, Maryland, United States
  • Elliott H Sohn
    Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Michelle Kelleher
    Oxford BioMedica, Oxford, United Kingdom
  • Richard Harrop
    Oxford BioMedica, Oxford, United Kingdom
  • Julie Loader
    Oxford BioMedica, Oxford, United Kingdom
  • Scott Ellis
    Oxford BioMedica, Oxford, United Kingdom
  • Kyriacos Mitrophanous
    Oxford BioMedica, Oxford, United Kingdom
  • Footnotes
    Commercial Relationships   Andreas Lauer, AGTC (F), Allergan (F), Genentech (F), NIH (F), Oxford BioMedica (F), SanofiFovea (F); Peter Campochiaro, Advanced Cell Technology (C), Aerpio (C), Alimera Sciences: (C), Applied Genetic Technologies (C), Asclipix (C), Eleven Biotherapeutics (C), Genentech (C), Gene Signal (C), Genzyme (S), GlaxoSmithKline (S), Kala Pharmaceuticals (C), Norvox (C), Oxford BioMedica (S), Regeneron (C), Rixi (C), Roche (C); Elliott Sohn, GlaxoSmithKline (S), Oxford BioMedica (S), Regeneron (S); Michelle Kelleher, Oxford BioMedica (E); Richard Harrop, Oxford BioMedica (E); Julie Loader, Oxford BioMedica (E); Scott Ellis, Oxford BioMedica (E); Kyriacos Mitrophanous, Oxford BioMedica (E)
  • Footnotes
    Support  Oxford BioMedica; Casey NIH Core grant (P30 EY010572) and Unrestricted grant from Research to Prevent Blindness
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Andreas K Lauer, Peter A Campochiaro, Elliott H Sohn, Michelle Kelleher, Richard Harrop, Julie Loader, Scott Ellis, Kyriacos Mitrophanous; Phase I Safety and Tolerability results for RetinoStat®, a Lentiviral Vector Expressing Endostatin and Angiostatin, in Patients with Advanced Neovascular Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):No Pagination Specified.

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

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Purpose : We investigated the safety and tolerability of RetinoStat®, a lentiviral vector-based therapy for the treatment of wet AMD, in a Phase I (GEM) study. The recombinant EIAV-based construct contains cDNAs for secretable endostatin and angiostatin to potentially inhibit angiogenesis in wet AMD subjects for whom anti-VEGF therapy is not sufficient. This is the first time in Man a lentiviral vector has been administered to the eye.

Methods : Twenty-one patients were treated (three dose groups (n=3) and final cohort at highest tolerated dose (n=12)) with active CNV at baseline and a best-corrected visual acuity (BCVA) ≤20/200 (for dose-escalation) or ≤20/80 (final cohort). BCVA in the fellow eye was ≥20/200. All patients had advanced stage disease with central subretinal fibrosis and poor anti-VEGF response despite an initially responsive medical history, the primary endpoint was therefore safety and tolerability. Secondary endpoints to assess signs of clinical benefit were also measured, and aqueous samples, taken throughout the study, were used to quantify transgene expression.

Results : Subretinal administration of RetinoStat® was well-tolerated at all three doses. There were no adverse events or severe adverse events related to drug or procedure. Inflammation, observed only at the highest dose, was graded mild and transient. RetinoStat® rapidly produced substantial, dose-dependent and persistent (out to >4 years so far) levels of both transgenes in the aqueous fluid. To our knowledge this is the first time a gene therapy delivered transgene product has been measured directly following administration to the eye. Vascular leakage, present in all subjects at baseline, was absent in the majority of patients at 6 and 12 months. Visual outcome showed little change across the trial in these advanced patients, potentially indicating disease stabilization.

Conclusions : RetinoStat® met the primary endpoint of the study: it was safe and well tolerated. Patients showed signs of clinical benefit, with visual acuity stabilization and a reduction in vascular leakage consistent with the mechanism of endostatin/angiostatin function in this severe wet AMD population. The data demonstrates that the LentiVector® gene therapy platform safely and efficiently delivers genes to the retina resulting in stable, long-term expression.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.


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