Retina Society 2023: Antiangiogenic Profile of Various Tyrosine Kinase Inhibitors

Jonathan Lin, MD, PhD
Mass Eye & Ear

At the 56th Annual Scientific Meeting of the Retina Society, Dr. Sophie Bakri from the Mayo Clinic shared her work titled “Comparison of the Antiangiogenic Profile of Tyrosine Kinase Inhibitors Vorolanib, Axitinib, and Sunitinib.” Therapies targeting vascular endothelial growth factor (VEGF) have been revolutionary for treating pathological angiogenesis as seen in many blinding diseases such as wet age-related macular degeneration.

Despite these successes, not all patients respond to anti-VEGF therapies, and these therapies can be a burden for patients and their caregivers since they sometimes require treatments as frequently as every 4-6 weeks.

One novel approach is the use of tyrosine kinase inhibitors (TKI). Instead of binding to VEGF in the extracellular space, TKIs bind to the VEGF receptor (VEGFR) and other receptor tyrosine kinases that may play a role in pathologic angiogenesis. In addition to having a broader potential therapeutic benefit, TKIs may also have a longer duration of effect, decreasing treatment burden.

Using the chorioallantoic membrane (CAM) assay for evaluation of angiogenesis, Dr. Bakri and colleagues confirmed that the TKIs vorolanib, axitinib, and sunitinib all effectively and similarly blocked angiogenesis.

However, Dr. Bakri emphasized that these three TKIs are not identical. Based on in vitro studies, axitinib was a potent inhibitor of the TIE-2 receptor (angiopoietin-1 receptor), and sunitinib was found to bind avidly to melanin. This may yield undesired off-target effects.

Given these in vitro and in vivo findings, Dr. Bakri hypothesized that vorolanib may be the optimal TKI. Additional studies are now underway.