EyePoint’s stock was down more than 70% Monday after its experimental treatment for wet age-related macular degeneration (wAMD) missed on its key goal in the first of two phase 3 readouts slated for this year.
The pharma is testing its drug-device combo, Duravyu, against Regeneron’s Eylea (aflibercept), the current standard of care for wAMD and an enduring blockbuster that grossed $4.4 billion in U.S. sales in 2025. But in results published Monday, EyePoint turned to an ad hoc analysis in an effort to salvage the tyrosine kinase inhibitor’s (TKI’s) performance in a phase 3 trial, in which Duravyu performed worse than the established treatment on a primary endpoint around best-corrected visual acuity (BVCA) at 52 and 56 weeks.
Based on EyePoint’s press release, the major falter appears to be vision loss that was not caused by wAMD.
Nine patients out of a cohort of 211 on Duravyu, or approximately 4%, experienced vision loss unrelated to wAMD over the course of the trial. But there was no such vision loss in the Eylea arm, a finding that Eyepoint CEO Jay Duker, M.D., called “highly unusual” given historical rates of 3% to 5% non-wAMD vision loss in past phase 3 trials, including those for Eylea. The company says these nine patients confounded the trial results, and when removed in an ad hoc analysis, Duravyu proved its non-inferiority to Eylea.
EyePoint’s aim with Duravyu is to offer vision benefits equal to that of anti-VEGFs like Eylea while potentially providing more durable delivery. In place of anti-VEGF injections, Duravyu’s ocular implant delivers the drug vorolanib in a sustained-release manner for at least six months, intended to give patients longer-lasting and more continuous relief.
The phase 3 misstep could undercut EyePoint’s ambition to displace Eylea as the high-value treatment of choice for wAMD, a leading cause of blindness in adults over 50, while putting significant pressure on the company’s identical Lucia trial expected to read out this fall.
But several analysts remain confident that a stronger performance in the second late-stage readout could redeem the company’s chances.
This is not EyePoint’s first run-in with disappointment, either. The treatment has been tested in a range of ophthalmology conditions. While it’s had successes with wAMD and diabetic macular edema (DME), the drug missed the mark in a study of patients with nonproliferative diabetic retinopathy (NPDR) in 2024.
While the findings may represent a strike against the drug’s potential approval, Citi analyst Yigal Nochomovitz said “extremely bad luck” may be a legitimate cause of the study’s poor outcome.
“There is precedent in ophthalmology for one failed trial and one successful trial to be sufficient for approval,” Nochomovitz said in an Aug. 17 note. “While we reflect higher LUCIA risk, we see a possible path forward in wAMD.”
And on secondary endpoints, Duravyu was strong. The TKI medicine exceeded expectations by decreasing injection burden by 42%, equating to two fewer injections on average compared to patients on Eylea. Duravyu also showed a strong safety profile and high supplement-free rates.
William Blair analysists said all the data together still suggest Duravyu offers “clinical benefit,” adding in a note that “one clean positive readout” could be enough to see EyePoint through its FDA green light. The fallout from today’s results, however, has bolstered shares of competitor Ocular Therapeutix by as much as 11% Monday.
Experts appear to agree that the future of Duravyu is now complicated but not finished. The good news: If it was bad luck, that kind of asymmetry is unlikely to repeat itself in another trial. But there are questions that now must be answered, namely what is behind the non-wAMD vision loss. For that, all eyes are on Lucia.
As EyePoint fights to make its case for Duravyu in the indication, Eylea’s reign in the category is being challenged. The anti-VEGF injection was approved for wAMD in 2011 and became an almost immediate blockbuster. While the drug still pulls its weight at Regeneron, biosimilars are crowding out the market. This year, the drug's quarterly sales dropped below $1 billion for the first time in eight years.