On this episode of Evidence Based Retina, Rishi Singh, MD, FASRS, is joined by and Murtaza Adam, MD, to discuss how tyrosine kinase inhibitors (TKIs) could revolutionize treatment options for retinal conditions like neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).
Dr. Adam, a vitreoretinal specialist at Colorado Retina Associates, also acted as a principal investigator in clinical trials such as LUCIA and subinvestigator in COMO, focusing on nAMD and DME.
Tyrosine kinase inhibitors: A brief overview
TKIs target enzymes critical to cellular processes such as growth and angiogenesis. In nAMD and DME, TKIs inhibit vascular endothelial growth factor (VEGF) receptors, which are key in pathological vascular growth.1
“But with TKIs, they are a small molecule. They work on the JAK pathway, so they inhibit IL-6, and on pan-VEGF suppression by inhibiting the VEGF 1 through 3 receptors and they work intracellularly. So, I think this class of drug may provide a bridge between steroid and anti-VEGF in getting a little bit more durability and again less saw toothing in those central subfield thickness (CST) fluctuations,” explained Dr. Adam.
TKIs in retinal disease management
Dr. Singh and Adam discussed central macular edema and noted that in patients with increased CST, greater CST fluctuations are associated with a higher likelihood of fibrosis and atrophy.
Although second-generation anti-VEGF drugs such as faricimab (VABYSMO, Genentech, a member of Roche) and aflibercept 8mg (EYLEA HD, Regeneron) extend treatment intervals, fluctuations persist in both clincial trial and real-world datasets. TKIs may smooth the CST trajectory for patients and help reduce the long-term visual decline observed in nAMD with established treatment options.
As Dr. Adam outlined, “We're looking for other ways to deliver improved durability and sustained control without the complications of surgery, without the risks of an implanted device, without the potential issues related to gene therapy and long-term expression and secondary inflammation. So TKIs, I think, have a lot of potential to really change expectations for patients and providers because of this multifaceted approach.”
DAVIO phase II clinical trial data on EYP-1901
Vorolanib targets multiple VEGFR isoforms and inhibits receptors such as the platelet-derived growth factor receptor (PDGFR) and the fibroblast growth factor receptor (FGFR), offering broad anti-angiogenic effects and reducing choroidal neovascularization. Delivered via a bioerodible system (Durasert) with consistent zero-order kinetics, it aims to maintain therapeutic levels in ocular tissues and reduce treatment frequency.1
In the DAVIO I and II trials, EYP-1901 was integrated with the Durasert drug delivery system to deliver sustained-release vorolanib directly to the posterior segment of the eye. The DAVIO phase II trial demonstrated that EYP-1901 reduced injection frequency by 85% in patients with nAMD, with >64% of eyes remaining supplemental-injection-free.1
Additionally, EYP-1901 is statistically non-inferior to the standard of care (SoC) in maintaining BCVA over 32 weeks. CST measurements for EYP-1901 were comparable to SoC, with 2mg increasing by 9.7μm and 3mg increasing by 5.2μm relative to the control.1
No EYP-1901-related serious ocular or systemic adverse effects, endophthalmitis, or retinal vasculitis were reported in DAVIO I and II.1 Moreover, “From a safety standpoint, preliminarily speaking, we have a lot of excitement and hope that this therapy will combine excellent outcomes visually and anatomically with premier safety,” Dr. Adam highlighted.
Treatment outlook
Clinical trials like DAVIO I and II show TKIs, such as EYP-1901, are effective and safe, reducing treatment burden and maintaining vision with fewer injections than standard anti-VEGF therapies.
The decreased treatment frequency has potential benefits for chronic nAMD and DME patients by improving adherence and quality of life, lessening logistical and psychological burdens.
