DAVIO 2: Dr. Regillo outlines the findings of EYP-1901 versus aflibercept in wet AMD
Carl Regillo, MD, Director of the Retina Service at Wills Eye Hospital in Philadelphia, gave an overview of a study he presented at the 2024 AAO Annual Meeting, titled “EYP-1901 for the Treatment of Neovascular AMD: Phase 2 DAVIO2 End-of-Study 12-Month Results.”
Carl Regillo, MD:
At this year’s American Academy of Ophthalmology Retina sub-day meeting, I presented for the first time to the podium, the end-of-study results to the DAVIO 2 phase 2 clinical trial. A little bit about what EYP-1901 is. That’s the product that was tested at both phase 1, that was the original DAVIO study, and this is the phase 2 DAVIO 2 clinical trial with EYP-1901.
EYP-1901 is vorolanib, a potent pan-VEGF tyrosine kinase inhibitor (TKI) molecule incorporated or combined with a completely bioerodible intravitreal insert. It’s a polymer. It’s injected intravitreally, and it’s designed to deliver the product vorolanib, the TKI, in a controlled release fashion, over a period of at least 6 months. Intravitreal injected sustained release of a TKI, or sustained delivery of the therapeutic. It was put to the test in a massed control prospective clinical trial, a Phase 2 study called DAVIO 2.
This clinical trial enrolled previously treated wet AMD patients and compared EYP-1901 to standard dosing aflibercept. It enrolled previously treated… Patients had to have at least 2 injections in the previous 6 months, and also a demonstrated response to anti-VEGF therapy. They were frequently treated but responsive, and they also had a certain range of visual acuity and OCT criteria. In the clinical trial, it’s a 3-arm study, randomized into 1 of these 3 arms. There are 2 doses of EYP-1901, and then the control arm was aflibercept; 161 patients were enrolled, so a little bit more than 15 each arm, and all arms received 3 monthly loading doses of standard dose aflibercept 2 mg and then EYP was injected at the third dose of aflibercept, the end of the loading phase. That’s week 8. One injection of EYP for the entire study.
In the aflibercept control arm, patients continue to get aflibercept on a frequent and regular basis every 2 months. Now, designed to release drug over at least 6, even 9 or more months, the primary endpoint of this clinical trial was mean change in BCVA from baseline to about seven7months or so, so that’s about 6 months after the EYP injection of that product. It was a non-inferiority trial and total timeframe in the clinical trial was 58 weeks, which is 14 months, which is what we’re presenting today for the first time. That’s end-of-study, and that represents 12 months from the point at which EYP-1901 was injected. As you would expect in a randomized, controlled study, all the arms were well-balanced. Patients had relatively good vision because they had been previously treated with anti-VEGF therapy, and mean visual acuity baseline was around 20/32. They were very high-need patients in terms of anti-VEGF therapy before enrollment. They averaged about 10 injections in the previous 12 months, and that was all 3 arms.
What did the study show? We had known previously that the trial was successful in reaching or meeting the primary endpoint of mean change in BCVA being statistically non-inferior at both doses compared to aflibercept at around that 6-month timeframe, 6 months after EYP was injected. Nearly equivalent types of BCVA readings we detected, and then we carried on in the study out to month 12 in the study, still looking nearly identical in terms of the BCVA vision curves, and then all the way out to month 14. Again, that represents 12 months from the time of the last EYP injections. Again, vision held up very well, and essentially the same between all three arms. Looking at OCT outcomes, very similar. The CST, central subfield thickness, was very stable in both EYP arms and comparable to aflibercept up to the primary endpoint, then to month 12, and again right out to the end of the study, month 14.
It’s also interesting to see, when you look at OCT, you see very steady curves in the 2 EYP arms. No significant fluctuation, but we’ve come to expect, and we do see, fluctuation or that so-called sawtooth pattern in the every-other-month aflibercept arm, indicative of activity in these patients. We also looked at the proportion of eyes not meeting supplemental criteria. In this clinical trial, it’s unique that all three arms, even the control arm, could get supplemented with aflibercept injections over time if they met criteria. What this study showed is even in the Q8 week aflibercept control arm, about a third of those patients by the end of the study actually met supplemental criteria. Many of these eyes, of course, therefore got extra doses of aflibercept through the course of the study. What about the EYP doses? Both, again, performed very well.
The proportion of patients not meeting supplemental criteria was up around two-thirds, 62% at month 8, and then right about 50% or so at month 12 in the study. Then, the final month 14, just about 40% or so. About half of the patients made it about 10 months from the last EYP injection, or the only EYP injection, without needing a supplement, which is pretty impressive. Treatment burden was greatly reduced in the clinical trial when you compared how many injections the aflibercept arm got versus the 2-way EYP arms. It was a 70% reduction in treatment burden. We look at treatment burden of these patients, each of the patients in the EYP, before they were enrolled. They’re again, very frequently treated. Over the course of the clinical trial, up to the end of the study at month 14, it was an 80% to 81% reduction in treatment burden compared to the prior 12 months. Again, also about 42%, 46% of patients were supplemental free over the 14 months.
Important to talk about safety. This is a new product. It is an intravitreal injection. They were minor AEs, mild, transient-related to the active injection, but EYP was really well-tolerated. There were no EYP-related ocular SAEs or systemic SAEs, no migration of the implant in the angioid chamber, no cases of retinal vasculitis or vascular occlusions, and no discontinuations in the arms for the EYP related to EYP, so really well-tolerated. What we learned is that now in summary, we have the DAVIO 2, which is the largest individual TKI trial to date. This is for the previously treated wet AMD patient population, and both doses showed very stable visual acuity and very strong anatomical outcomes over the entire course of 14 months in this phase 2 trial. In both arms combined that got EYP, about 63% at 6 months, 44% at 12 months, were supplemental injection-free, could go just with EYP to control disease adequately.
This effectively also translated into about an 80% reduction in treatment burden compared to pre-trial treatment, and all this was with a product that was really very well tolerated. With those results, a very favorable efficacy and safety results from the phase 2 and phase 1 programs, we’re now on the cusp of launching the pivotal phase 3 program, LUGANO and LUCIA phase 3 clinical trials. This is EYP at the higher dose used in DAVIO 2 compared to aflibercept head-to-head, large scale, global, non-inferiority clinical trials. Three loading doses, combination of previously treated and treatment-naive wet AMD patients. The big difference here, it’s a longer term, larger study of course, but it’s also multiple dosing of EYP at an interval of every 6 months compared to aflibercept dosed in the usual fashion every eight weeks. Really exciting to see the product go into phase 3 after a very successful phase 2 program. Thank you very much.
