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  • Topical VEGFr antagonist does not reduce need for intravitreal ranibizumab

    Retina/Vitreous

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    Review of: 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

    Poor S, Weissgerber G, Adams C, et al. American Journal of Ophthalmology, March 2022

    This multicenter, phase 2 randomized, double-masked study examined the efficacy of topical acrizanib in reducing the need for intravitreal anti-VEGF therapy in patients with neovascular AMD (nAMD).

    Study design

    This phase 2 randomized, double-masked study evaluated whether topical acrizanib (LHA510) could reduce the need for intravitreal ranibizumab in patients with nAMD during a 12-week interval. Acrizanib is a topical VEGF receptor (VEGFr) inhibitor. Eyes were treated with intravitreal ranibizumab, and then randomized 1:1 to either topical acrizanib (twice daily for 8 weeks, then 3 times daily over the last 4 weeks) or vehicle control. Outcome measures were the number of eyes needing additional intravitreal ranibizumab injections during the12-week period, the number of injections needed, time to next injection, and change in visual acuity and central subfield thickness (CSFT).

    Outcomes

    In the analyzed efficacy dataset, 25 patients in the acrizanib group (75.8%) and 25 patients in the vehicle group (67.6%) required additional intravitreal ranibizumab injections in the 12-week study period. Additionally, no significant differences between acrizanib and vehicle were observed with regard to the number of injections, time to next injection, CSFT reduction, or change in visual acuity.

    Limitations

    This study recruited patients who were dependent on intravitreal anti-VEGF treatment at least every 8 weeks, and who had a mean of 24 months since initial nAMD diagnosis. Thus, this treatment-dependent population may have limited the ability to show efficacy of acrizanib. Only ranibizumab-treated patients were included. Also of note, 21 of 46 patients treated with acrizanib developed a reversible corneal haze during the treatment course.

    Clinical significance

    In this phase 2 study, acrizanib did not suppress the need for intravitreal ranibizumab in eyes with nAMD. At this time, topical therapy for nAMD, despite promising data from pre-clinical studies and animal models, has not yet demonstrated efficacy in human trials. Surface-related adverse events would be of interest in future studies of topical therapies for nAMD.