June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Rationale for Treating Wet AMD in Human Using an Oral Pill Consisting of a VEGFR/PDGFR Inhibitor X-82
Author Affiliations & Notes
  • Chris Liang
    Xcovery, LLC, West Palm Beach, FL
  • David Brown
    Retina Consultants of Houston, Houston, TX
  • Nauman Chaudhry
    New England Retina Associates, New London, CT
  • Michael Elman
    Elman Retina Group, Baltimore, MD
  • Jeffrey Heier
    Ophthalmic Consultants of Boston, Boston, MA
  • Footnotes
    Commercial Relationships Chris Liang, Xcovery, LLC (E); David Brown, Regeneron Pharmaceuticals, Inc. (F), Regeneron Pharmaceuticals, Inc. (C), Regeneron Pharmaceuticals, Inc. (R), Bayer HealthCare (F), Bayer HealthCare (C), Bayer HealthCare (R), Genentech (C), Roche (C), Alimera (C), Alcon (C), Novartis (C), Thrombogenics (C), Genentech (F), Roche (F), Thrombogenics (F), GSK (F), Alimera (F), Alcon (F), Allergan (F), Eli Lilly (F); Nauman Chaudhry, Genentech (F), Regeneron Pharmaceuticals (F), Xcovery Vision (F), Lpath (F), DRCR network (F); Michael Elman, Genentech (C), Ohr Pharmaceuticals (I), Novartis (F), DRCRnet (F); Jeffrey Heier, Acucela (C), Aerpio (C), Alimera (F), Allergan (C), Bayer (C), Forsight Labs (C), Fovea (F), Genentech (C), Genzyme (C), Genentech (F), Genzyme (F), Thrombogenics (C), Sequenom (C), Notal Vision (F), Novartis (F), Ophthotech (F), Ophthotech (C), Oraya (C), Paloma (F), Regeneron (F), Regeneron (C)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 3272. doi:
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      Chris Liang, David Brown, Nauman Chaudhry, Michael Elman, Jeffrey Heier; Rationale for Treating Wet AMD in Human Using an Oral Pill Consisting of a VEGFR/PDGFR Inhibitor X-82. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3272.

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

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Purpose: To analyze the pre-clinical and clinical safety and biologic activity of X-82, a VEGFR/PDGFR inhibitor.

Methods: X-82 was evaluated in vitro and via oral administration in a rat CNV model, focusing on safety and biologic activity. The safety and pharmacokinetic properties of X-82 in cancer patients were analyzed to define the doses that might be safe and effective in AMD patients.

Results: VEGFR and PDGFR inhibition occurred with <50 nM in the HUVEC tube formation model. In the rat CNV model, 10 mg/kg dosed orally once a day showed >80% inhibition of CNV. Oral administration of X-82 in cancer patients was well tolerated with no Grade 2 or higher toxicities at exposures of 5191 ng.hr/ml and Cmax of 942 nM. At 50mg once a day, the mean AUC, Cmax and Ctrough levels were 1282 ng.hr/ml, 268 nM and 41 nM, respectively.

Conclusions: Oral administration of X-82 at 50mg once a day achieved exposures well above the concentration required to inhibit new blood vessel formation; this level was < ¼ of the well tolerated exposure noted in cancer patients, suggesting that the dose should be well tolerated and could be efficacious in treating wet AMD patients. A pilot clinical study of X-82 in patients with wet AMD has started.

Keywords: 412 age-related macular degeneration • 453 choroid: neovascularization • 748 vascular endothelial growth factor  

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