June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Effects of the multi-kinase inhibitor regorafenib on ocular neovascularization
Author Affiliations & Notes
  • Juergen Klar
    Ophthalmology, BAYER Pharma AG, Wuppertal, Germany
  • Michael Karl Boettger
    Clinical Sciences Experimental Medicine, BAYER Pharma AG, Wuppertal, Germany
    Ophthalmology, BAYER Pharma AG, Wuppertal, Germany
  • Julia Freundlieb
    BAYER Pharma AG, Wuppertal, Germany
  • Joerg Keldenich
    BAYER Pharma AG, Wuppertal, Germany
  • Pierre-Paul Elena
    IRIS Pharma, Nice, France
  • Georges von Degenfeld
    Ophthalmology, BAYER Pharma AG, Wuppertal, Germany
  • Footnotes
    Commercial Relationships Juergen Klar, Bayer (E), Bayer (P); Michael Boettger, Bayer (E), Bayer (P); Julia Freundlieb, Bayer (E), Bayer (P); Joerg Keldenich, Bayer (E), Bayer (P); Pierre-Paul Elena, IRIS Pharma (E); Georges von Degenfeld, Bayer (E), Bayer (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 246. doi:
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      Juergen Klar, Michael Karl Boettger, Julia Freundlieb, Joerg Keldenich, Pierre-Paul Elena, Georges von Degenfeld; Effects of the multi-kinase inhibitor regorafenib on ocular neovascularization. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):246.

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

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Purpose: Regorafenib is a multi-kinase inhibitor that potently blocks VEGF receptor signaling. Here, we investigated the efficacy of regorafenib on ocular neovascularization in two disease-relevant models of wet AMD in two species.

Methods: Different doses of regorafenib administered p.o. or topically in early and delayed treatment regimens were tested regarding the reduction of vascular leakage and/or neovascularization in the rat laser-induced choroidal neovascularization (CNV) model. As a second disease-relevant model, the oxygen induced mouse retinopathy (OIR) model was employed.

Results: Regorafenib showed dose-dependent reduction of vascular leakage and neovascularization in the rat CNV model. The mean angiography score in the control group was 2.4±0.8 (all data presented as mean±SD; n=8) and was reduced to 2.4±0.7, 2.2±0.8 and 1.5±0.8 (n= 8) by Regorafenib at 1, 3 and 8 mg/kg, respectively. The volume of choroidal neovascularization was likewise reduced from 210209±52055 μm³ (n= 8) in the untreated rats to 192662±52055 μm³, 182360±97054 μm3 and 114256±37265 μm³ (n= 8) compared to the rats dosed with 1, 3 and 8 mg/kg Regorafenib PO, respectively. Regorafenib at 8mg/kg also significantly reduced vascular leakage and neovascular volume at day 21 when treatment start was delayed to 7 days after laser injury. In this delayed setup the mean score in the control group was 1.96±0.55 (n=6) and reduced to 1.1±0.28 by 8mg/kg Regorafenib (n=8; p=0.0012). The volume of choroidal neovascularization was 366729±76875 μm³ (n=6) in the vehicle group and reduced to 143234±114156 μm³ (n=8; p=0.0025) by 8 mg/kg Regorafenib.<br /> In addition, Regorafenib formulated as an eye drop suspension at 20 mg/mL, administered twice daily, reduced vascular leakage and neovascularization by 30.6% and 34.0% (p<0.0001), respectively, when compared to controls in the rat laser CNV model.<br /> In the OIR model the retinal vessel area was 45.3% ± 7.0% (mean±SD; n=19) for the control group and reduced by Regorafenib (2.5 mg/kg) or Regorafenib (10 mg/kg) administered IP once daily to 29.0% ± 11.1% (n=17; p<0.0001) or 17.9% ± 6.0% (n=17; p<0.0001), respectively.

Conclusions: Currently available treatment options require injection(s) into the eye by a physician. An eye drop formulation would be non-invasive and self-administered by patients. Regorafenib shows efficacy in two different rodent models of ocular neovascularisation.


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