No added benefit with pazopanib over ranibizumab for neovascular AMD

By Lucy Piper, Senior medwireNews Reporter

Pazopanib eye drops do not enhance visual outcomes in patients with neovascular age-related macular degeneration (AMD) beyond those achieved with ranibizumab alone, study findings indicate.

Pazopanib, a multitarget tyrosine kinase inhibitor, not only inhibits vascular endothelial growth factor (VEGF) receptors 1, 2 and 3, but also the pro-angiogenic platelet-derived growth factor pathway, an important target in preventing angiogenesis, an key factor in the progression of AMD.

Researchers John Wurzelmann (GlaxoSmithKline, Research Triangle Park, North Carolina, USA) and colleagues therefore considered whether daily eye drops of the drug could reduce the need for intravitreal injections of the VEGF inhibitor ranibizumab while still maintaining or improving vision.

A total of 510 patients with active subfoveal choroidal neovascularisation secondary to AMD who had previously managed their condition with anti-VEGF treatment, were randomly assigned to one of seven treatment groups.

The treatment regimens received were: placebo eye drops four times a day (n=73); pazopanib 5 mg/mL eye drops three (n=72) or four (n=74) times a day; pazopanib 10 mg/mL two (n=73), three (n=73) or four (n=72) times a day; or ranibizumab injection administered once every 4 weeks (n=73). All the patients were able to receive open-label ranibizumab as needed.

At week 52 of follow-up, the patients receiving pazopanib eye drops had a mean best-corrected visual acuity gain of 0.3 to 1.8 letters from baseline. This compared with a gain of 0.2 letters for those given placebo and as-needed ranibizumab and 1.4 letters for patients given ranibizumab injections.

Each dosing regimen of pazopanib eye drops plus as-needed ranibizumab was therefore non-inferior to monthly ranibizumab plus as-needed ranibizumab alone, the researchers report.

They add in Ophthalmology that pazopanib also did not significantly reduce the need for ranibizumab injections, failing to meet the pre-specified criterion of at least a 50% reduction. The average annual injection rate was 8.5 for the placebo eye drop group and between 7.2 and 8.6 for the pazopanib groups.

The lack of additional benefit with pazopanib was not explained by the AMD risk genotype, complement factor H Y402H, which had no effect on treatment response. This is consistent with findings from the recent Comparison of AMD Treatments Trials reports, notes the team.

These reports also found no difference between as-needed and monthly injections, leading Wurzelmann and team to conclude that together with their findings, “[t]hese data collectively suggest that as-needed treatment, accompanied by continuing observation, is a reasonable approach relative to monthly injections recommended for bevacizumab and ranibizumab.”

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