Acrizanib Shows No Benefit for Neovascular Age-Related Macular Degeneration

Topical acrizanib (LHA510), a small molecule vascular endothelial growth factor (VEGF) receptor inhibitor, failed to suppress the need for anti-VEGF therapy in patients with neovascular age-related macular degeneration (AMD) compared with placebo, according to study findings published in the American Journal of Ophthalmology.

“Despite a multi-year program of medicinal chemistry optimization for topical delivery, impressive topical ocular exposure, and efficacy in preclinical models, topical LHA510 had no demonstrable benefit reducing neovascular AMD disease activity in patients,” wrote lead and corresponding author Stephen H Poor, PhD, of the Novartis Institutes for Biomedical Research, and coauthors.

The phase 2 study included 90 patients with active choroidal neovascularization due to neurovascular AMD under anti-VEGF treatment. Patients received intravitreal ranibizumab at baseline and were retreated at evidence of disease recurrence. Patients were randomized to receive topical LHA510 or placebo for 12 weeks. For the first 8 weeks, drops were administered twice a day. During the last 4 weeks, administration increased to 3 times a day.

Compared with 67.6% of the placebo group, 75.8% of patients in the LHA510 group required ranibizumab rescue for evidence of disease recurrence by week 12, according to study authors.

Key secondary efficacy endpoints, including time to first rescue, total number of ranibizumab injections, and changes in central subfield thickness and visual acuity, did not suggest benefit with LHA510 over placebo either.

Furthermore, 21 of 46 patients who received LHA510 developed a reversible corneal haze. The haze resolved with treatment cessation and did not recur in participants who restarted drops at a reduced once-daily frequency.

“Given the large number of trials of topical therapies for neurovascular AMD that have failed, and given that topical efficacy in standard preclinical VEGF dependent ocular models does not predict human efficacy, topical VEGF therapy targeting retinal cells may be beyond reach,” wrote researchers. “Perhaps the best chance to improve patient compliance and real-world efficacy would be to develop therapies that more directly target chorioretinal tissues and/or show prolonged durability, many of which are in clinical development.”

Reference:
Poor SH, Weissgerber G, Adams CM, et al. A randomized, double-masked, multicenter trial of topical acrizanib (LHA510), a tyrosine kinase VEGF-receptor inhibitor, in treatment-experienced subjects with neovascular age-related macular degeneration. Am J Ophthalmol. Published online March 2, 2022. doi:10.1016/j.ajo.2022.02.019