September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Systemic Pharmacodynamic Effects of Anti-Vascular Endothelial Growth Factor (VEGF) Agents in Patients With Wet Age-Related Macular Degeneration
Author Affiliations & Notes
  • Peter K Kaiser
    Ophthalmology, Cole Eye Institute, Cleveland, Ohio, United States
  • Laurent Kodjikian
    Hopital de la Croix-rousse, Lyon, France
  • Jean-Francois Korobelnik
    Université de Bordeaux, Bordeaux, France
  • Oliver Zeitz
    Bayer Pharma AG, Berlin, Germany
  • Robert Vitti
    Regeneron Pharmaceutical Inc., Tarrytown, New York, United States
  • Carola Metzig
    Bayer Pharma AG, Berlin, Germany
  • Christiane Ahlers
    Bayer Pharma AG, Berlin, Germany
  • Thomas dicioccio
    Regeneron Pharmaceutical Inc., Tarrytown, New York, United States
  • Joachim Hoechel
    Bayer Pharma AG, Berlin, Germany
  • Footnotes
    Commercial Relationships   Peter Kaiser, Bayer Healthcare (C); Laurent Kodjikian, Bayer Healthcare (C); Jean-Francois Korobelnik, Alcon (C), Alimera (C), Allergan (C), Bayer Healthcare (C), Horus (C), Novartis (C), Roche (C), Thea (C), Zeiss (C); Oliver Zeitz, Bayer Pharma AG (E); Robert Vitti, Regeneron Pharmaceuticals Inc. (E); Carola Metzig, Bayer Pharma AG (E); Christiane Ahlers, Bayer Pharma AG (E); Thomas dicioccio, Regeneron Pharmaceuticals Inc. (E); Joachim Hoechel, Bayer Pharma AG (E)
  • Footnotes
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Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3366. doi:
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      Peter K Kaiser, Laurent Kodjikian, Jean-Francois Korobelnik, Oliver Zeitz, Robert Vitti, Carola Metzig, Christiane Ahlers, Thomas dicioccio, Joachim Hoechel; Systemic Pharmacodynamic Effects of Anti-Vascular Endothelial Growth Factor (VEGF) Agents in Patients With Wet Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3366.

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

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Abstract

Purpose : To evaluate systemic pharmacodynamic effects of intravitreal aflibercept injection (IAI) and intravitreal ranibizumab (RBZ) in patients (pts) with wet age-related macular degeneration (wAMD) enrolled in 3 large Phase 3 studies.

Methods : Data from the 2-year VIEW 1/2 (N=2419) studies and the 1-year SIGHT (N=304) study were included. VIEW 1/2 compared 3 IAI doses (0.5q4, 2q4, and 2q8) and 1 dose of RBZ (R0.5q4); SIGHT compared IAI 2q8 with photodynamic therapy (PDT) (from Week 28 pts on PDT switched to IAI). We investigated changes from baseline to study end in systolic and diastolic blood pressure (S/DBP) and kidney function, a highly sensitive pharmacodynamic marker for potential VEGF inhibition, in these trials.

Results : Across all studies/treatments, there was no meaningful change from baseline in mean (SD) SBP (VIEW 1/2 [R0.5q4, –3.3 mmHg (18.1); 2q4, –2.9 mmHg (17.9); 0.5q4, –2.9 mmHg (18.1); 2q8 –4.2 mmHg (18.3)]; SIGHT [2q8, –0.2 mmHg (12.8); PDT, 0.1 mmHg (12.9)]) and DBP (data not shown) over the course of the studies. Additionally in SIGHT, there was no change in mean SBP and DBP after pts in the PDT arm were switched to IAI 2q8 at Week 28. In IAI-treated pts in VIEW, BP was evaluated relative to free aflibercept in plasma. Maximum plasma concentrations of free aflibercept (systemic Cmax) were low (mean 0.02 μg/mL [0–0.054 within 1–3 days after a 2 mg intravitreal injection]) and undetectable 2 weeks following dosage in most pts. Systemic aflibercept exposure did not correlate with BP changes or with BP-related adverse events (AEs). For all arms, there was no change from baseline in mean (SD) kidney function, as assessed by urine protein-creatinine ratio (VIEW1/2 [R0.5q4, 1.950 mg/mmol (40.401); 2q4, –0.043 mg/mmol (27.081); 0.5q4, 0.899 mg/mmol (29.666); 2q8, 1.977 mg/mmol (28.231)]; SIGHT [2q8, –0.094 mg/mmol (9.930); PDT, 1.329 mg/mmol (7.843)]). The absence of systemic pharmacodynamic effects is consistent with the low number of systemic AEs, including arterial thromboembolic events, showing no difference between IAI and control.

Conclusions : Given the sensitivity of BP changes and kidney function as a proxy for systemic anti-VEGF activity, the data from 3 large Phase 3 studies indicate the absence of systemic pharmacodynamic effects due to exposure to RBZ or IAI.

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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