Safety and tolerability of oral vorolanib for neovascular (wet) age-related macular degeneration: a phase I, open-label study

Objective To evaluate the efficacy and safety of oral vorolanib for the treatment of neovascular (wet) age-related macular degeneration (nAMD). Methods In the dose escalation, participants received ascending doses of oral vorolanib (25–100 mg daily). In the dose expansion, participants received recommended doses (25 and 50 mg daily). Results Between March 15, 2015, and January 23, 2019, 41 participants were enrolled in 6 centres in China. At the data cut-off (November 14, 2019), two dose-limiting toxicities (DLTs) were observed during dose escalation (one in the 75 mg cohort and one in the 100 mg cohort). The maximum tolerated dose was not reached. Treatment-related adverse events (TRAEs) occurred in 33 (80.5%) participants, and grade 3 or higher TRAEs occurred in 12 (29.3%) participants. No fatal TRAEs were observed. Increases in the mean best-corrected visual acuity (BCVA) from baseline to Day 360 of +7.7 letters (range, −5–29; n = 41) were observed in participants who were administered vorolanib. Corresponding reductions in mean central subfield thickness (CST) and choroidal neovascularization (CNV) area at Day 360 were observed in these three groups. Conclusions Oral administration of vorolanib improved visual outcomes in participants with nAMD with manageable systemic safety profiles.