Hawaiian Eye Meeting update: TKI therapy may reduce treatment burden in DME and wet AMD
Sumit Sharma, MD, of the Cleveland Clinic, spoke with Ophthalmology 360 about a presentation he gave at the Hawaiian Eye meeting on the latest clinical trial updates on the experimental treatment, vorolanib, for age-related macular degeneration and diabetic macular edema.
Sumit Sharma, MD:
My name is Sumit Sharma. I’m a retina specialist at Cleveland Clinic Cole Eye Institute, and I serve as the vice chair in the department as well. At Hawaiian Eye, I had the opportunity to present on EYP-1901, which is the vorolanib intravitreal insert for retinal exudated diseases. I gave an update on the status of the clinical trial.
EYP-1901 is a bioerodible intravitreal insert that provides sustained release of the tyrosine kinase inhibitor vorolanib over a 6-month period. Vorolanib is very interesting because it has a novel mechanism of action that blocks both VEGF signaling and IL-6 signaling. It has immediate release. You see levels of voralanib at therapeutic levels within hours after injection, and it lasts for at least 6 months with no free-floating drug particles as it releases and no cold storage required, and it ships in a preloaded intravitreal injector.
EYP-1901 or voralanib is very interesting in that it’s different from other anti-VEGFs in that it actually is a tyrosine kinase inhibitor, so it’s a small molecule, that works intracellularly to block VEGF signaling through all of the VEGF receptors. You get pan-VEGF inhibition, but it also blocks JAK1. By blocking the JAK1 receptor, you also block IL-6 signaling. We know in retinal vascular diseases and retinal exudative diseases that IL-6 plays a huge role, especially in those eyes that tend to be poor treatment responders to anti-VEGF alone. By using voralanib, you could potentially target both pathways. This has been looked at in a number of trials in both phase 1 and phase 2. In phase 1, the DAVIO study looked at patients with wet AMD, and then in phase 2, DAVIO-2 looked at patients with wet AMD who had previously been treated. In VERONA, they looked at patients with DME. The phase 3 program is ongoing.
The phase 3 program for EYP-1901, for LUGANO and LUCIA, are 2 paired phase 3 clinical trials that are comparing EYP-1901 to aflibercept. All patients get 3 doses of aflibercept injections run-in, and then they get randomized to either continue on aflibercept every 8 weeks or get 1 EYP-1901 injection every 6 months with a primary endpoint at 1 year. If we look at the phase 2 data in DAVIO-2, we see that with a similar setup after those initial aflibercept run-in injections, once patients got EYP-1901, they maintained the same vision and the same central retinal thickness over that 6-month period despite not needing another treatment compared to the aflibercept arm, which was getting every 8-week injections. The percentage of patients who needed supplemental criteria was fairly low across the board. Then if you look at the tighter supplemental criteria that were used in LUGANO and LUCIA, and you apply those to the phase 2 program that you see, that supplemental injection rate was even lower and would’ve been between 13% and 20% for EYP-1901, depending on which dose you looked at.
But if you look at the phase 3 dose, it’ll be closer to about 13%, which is fantastic because that means that over a 6-month period, only about 1 in 8 to 1 in 10 patients will need a supplement after getting that initial anti-VEGF run-in. We’re excited to see what the phase 3 program will show. We should have results later this year because both of the LUGANO and LUCIA studies are fully enrolled, and we expect top-line results probably in Q3 or Q4 this year.
Then the DME program, VERONA, is kicking off and should be enrolling patients starting this year. Sorry, the phase 2 program is COMO and CAPRI. VERONA was the phase 2, but excited to see the results. Excited to see what happens. I think that there was in the past some trepidation about TKIs, but I think with this formulation, we should see some interesting results moving forward.
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