Pazopanib shows therapeutic potential as treatment for AMD

Oral pazopanib - in a dose of 15 mg/d - is well tolerated and may improve mean best-corrected visual acuity (BCVA), central retinal lesion thickness, and central retinal thickness in as little as 1 month of treatment in some patients with age-related macular degeneration (AMD), according to study results published October 2013 in JAMA Ophthalmology (formerly Archives of Ophthalmology). Further, researchers postulate that the CFH Y402H genotype may predict patient response to pazopanib.

Pazopanib is an antiangiogenic multitargete tyrosine kinase inhibitor of VEFG receptors 1, 2, and 3, platelet-derived growth factor receptors α and β, and the stem cell factor receptor, c-kit. In oncology, pazopanib (Votrient) has been approved for use in doses of 800 mg once daily in certain cancers.

For this study, researchers included 72 healthy subjects in the 14-day, placebo-controlled, dose-rising arm of the study, and 15 patients with subfoveal choroidal neovascularization secondary to AMD in a 28-day phase 2a open-label study. Healthy patients were treated with oral pazopanib tables (5 to 30 mg/d), in either a single dose of 5, 10, 20, or 30 mg (n =6 per cohort), or repeated doses of 5, 10, 20, or 30 mg (n = 9 per cohort), or placebo (n =3 per cohort) once daily for 14 days. In the repeated-dose portion, subjects received either pazopanib or placebo in a 3:1 ratio according to the randomization done prior to study initiation. Patients with AMD received pazopanib in a dose of 15 mg/d.

Both groups tolerated pazopanib well, but 6 of 15 patients received rescue therapy before day 29; all of these patients carried the CFH Y402H CC 'high-risk' genotype for AMD. Nine patients completed the study without rescue, and improved from baseline in BCVA by 8 Early Treatment Diabetic Retinopathy Study letters, in central retinal lesion thickness (-50.94 μm), and central retinal thickness (-50.28 μm).

Researchers found a trend for association between the CFH Y402H T allele, or the 'low risk for AMD' genotype (n = 6) and improvement.

To access the results of this study, click here.

This study was funded by GlaxoSmithKline.