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.

 

Comments:

The objective of the study was to evaluate the efficacy and safety of oral vorolanib for the treatment of neovascular (wet) age-related macular degeneration (nAMD). The study employed a two-part design consisting of dose escalation and dose expansion phases.

In the dose escalation phase, participants received ascending doses of oral vorolanib ranging from 25 to 100 mg daily. In the dose expansion phase, participants received the recommended doses of 25 and 50 mg daily.

Between March 15, 2015, and January 23, 2019, a total of 41 participants were enrolled in six centers in China. The data cut-off was on November 14, 2019. During the dose escalation phase, two dose-limiting toxicities (DLTs) were observed—one in the 75 mg cohort and one in the 100 mg cohort. However, the maximum tolerated dose was not reached.

Treatment-related adverse events (TRAEs) occurred in 33 (80.5%) participants, but no fatal TRAEs were observed. Grade 3 or higher TRAEs occurred in 12 (29.3%) participants. These results suggest that while there were adverse events associated with the treatment, they were generally manageable.

The study found that participants who were administered vorolanib experienced increases in mean best-corrected visual acuity (BCVA) from baseline to Day 360. The improvement in BCVA was measured as a mean increase of 7.7 letters, with a range of -5 to 29 letters. Furthermore, reductions in mean central subfield thickness (CST) and choroidal neovascularization (CNV) area at Day 360 were observed in these participants.

Based on these findings, the study concluded that oral administration of vorolanib improved visual outcomes in participants with nAMD, and the systemic safety profiles were manageable. However, it is important to note that these conclusions are based on the specific study conducted in China, and further research may be necessary to validate the findings and assess the generalizability of the results.

Related Products

Cat.No.	Product Name	Information
S6843	Vorolanib	Vorolanib (X-82,CM082) is an oral, multikinase, dual inhibitor of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) with antiangiogenic and antineoplastic activities.

Related Targets

PDGFR VEGFR