Ranibizumab Combined With Low-Dose Sorafenib for Exudative Age-Related Macular Degeneration

Diago, Teresa; Pulido, José S.; Molina, Julian R.; Collet, Lucienne; Link, Thomas P.; Ryan, Edwin H.

doi:10.4065/83.2.231

Cited by 16 publications

(4 citation statements)

References 8 publications

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“…There are a number of approved orally administered VEGFR-2 inhibitors for oncology indications and several have been investigated in wet AMD. − In a published case study, treatment with oral sorafenib correlated with reduced retinal edema and increased visual acuity. , More recently, orally dosed pazopanib is reported to improve vision, reduce edema, and reduce neovascularization in wet AMD patients . Despite the fact the doses used were markedly less than those in oncology indications, systemic side effects were still observed.…”

Section: Introductionmentioning

confidence: 99%

Discovery of Oral VEGFR-2 Inhibitors with Prolonged Ocular Retention That Are Efficacious in Models of Wet Age-Related Macular Degeneration

Meredith¹,

Mainolfi²,

Poor³

et al. 2015

J. Med. Chem.

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The benefit of intravitreal anti-VEGF therapy in treating wet age-related macular degeneration (AMD) is well established. Identification of VEGFR-2 inhibitors with optimal ADME properties for an ocular indication provides opportunities for dosing routes beyond intravitreal injection. We employed a high-throughput in vivo screening strategy with rodent models of choroidal neovascularization and iterative compound design to identify VEGFR-2 inhibitors with potential to benefit wet AMD patients. These compounds demonstrate preferential ocular tissue distribution and efficacy after oral administration while minimizing systemic exposure.

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Section: Introductionmentioning

confidence: 99%

Discovery of Oral VEGFR-2 Inhibitors with Prolonged Ocular Retention That Are Efficacious in Models of Wet Age-Related Macular Degeneration

Meredith¹,

Mainolfi²,

Poor³

et al. 2015

J. Med. Chem.

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“…This patient experienced improvement of exudative AMD after use of a standard dose of sorafenib for the cancer. In addition, Diago et al 35 described two patients with exudative AMD who needed multiple ranibizumab injections and who elected to receive an off-label sorafenib added to the standard treatment in an attempt to decrease the number of intraocular injections. Marked improvement of macular oedema was noted in both patients based on the use of optical coherence tomography.…”

Section: Discussionmentioning

confidence: 99%

Effect of sorafenib on experimental choroidal neovascularization in the rat

Park¹,

Roh

Lee³

2010

Clinical Exper Ophthalmology

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Purpose: This study was designed to evaluate the effect of sorafenib administration on laser-induced experimental choroidal neovascularization (CNV) in rats.Methods: A total of 36 rats were divided into three groups. Sorafenib, an oral, multitargeted receptor tyrosine kinase inhibitor, was administered at a dose of 10 mg/kg per day (n = 12) or 30 mg/kg per day (n = 12) for 1 day before the laser induction of CNV. Rats continued to receive the drug for 14 days. Fluorescein angiograms were analysed for CNV dye leakage and the thickness of CNV was assessed by histology. The levels of vascular endothelial growth factor, platelet-derived growth factor, monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 mRNA were measured by the use of real-time quantitative reverse-transcription polymerase chain reaction.Results: Sorafenib-treated rats had significantly less fluorescence leakage as compared with vehicletreated rats (P < 0.05), The CNV thickness in sorafenib-treated rats was significantly reduced as compared with vehicle-treated rats in a dosedependent manner (P = 0.00163 for 10 mg/kg and P < 0.00001 for 30 mg/kg). After sorafenib (30 mg/ kg) administration, expression of the vascular endothelial growth factor and intercellular adhesion molecule-1 genes was significantly decreased (P < 0.05 and P = 0.00802). Conclusion:These results suggest that sorafenib may be potentially beneficial for the treatment of CNV in human; further studies on this subject are warranted.

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“…Diago et al also described two patients with neovascular AMD whose ranibizumab therapies were combined with oral sorafenib. 38 Both patients experienced stability or improvement in vision and a marked improvement on optical coherence tomography. One of the patients showed a marked improvement in intraretinal oedema after taking sorafenib.…”

Section: Baselinementioning

confidence: 90%

Effect of cediranib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a mouse model of choroidal neovascularization

Kang

Park

Yang

et al. 2012

Clinical Exper Ophthalmology

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Ranibizumab Combined With Low-Dose Sorafenib for Exudative Age-Related Macular Degeneration

Cited by 16 publications

References 8 publications

Discovery of Oral VEGFR-2 Inhibitors with Prolonged Ocular Retention That Are Efficacious in Models of Wet Age-Related Macular Degeneration

Discovery of Oral VEGFR-2 Inhibitors with Prolonged Ocular Retention That Are Efficacious in Models of Wet Age-Related Macular Degeneration

Effect of sorafenib on experimental choroidal neovascularization in the rat

Effect of cediranib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a mouse model of choroidal neovascularization

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