EyePoint’s DURAVYU Misses Primary Endpoint in Phase III Wet AMD Trial

Key Points

• EyePoint’s DURAVYU missed the primary endpoint in the Phase III LUGANO wet AMD trial, failing to demonstrate non-inferiority to aflibercept in the full analysis population. The company attributed much of the gap to nine DURAVYU patients who suffered significant vision loss from conditions unrelated to wet AMD.
• DURAVYU showed a 42% reduction in treatment burden through week 56, with 54% of treated eyes remaining supplement-free for one year and roughly 90% requiring no more than two supplemental injections. EyePoint also reported similar anatomic control and a favorable safety profile, though floaters were more common than with aflibercept.
• EyePoint remains focused on its second Phase III trial, LUCIA, with results expected in the fourth quarter. If positive, the company expects to discuss its data package with the FDA and potentially file for approval in the first half of 2027.

Eyepoint Pharmaceuticals NASDAQ: EYPT reported topline results from LUGANO, the first of two Phase III trials evaluating DURAVYU, a vorolanib intravitreal insert, in patients with wet age-related macular degeneration, or wet AMD. The study did not meet its primary non-inferiority endpoint in the full analysis population versus on-label aflibercept.

LUGANO enrolled 432 patients, randomized equally to DURAVYU 2.7 mg administered every six months or aflibercept administered every other month after an initial monthly EYLEA loading regimen. The primary endpoint measured non-inferiority in mean change in best-corrected visual acuity from day one through averaged weeks 52 and 56, using a non-inferiority margin of negative 4.5 letters.

Primary Endpoint Missed in Full Population

According to Chief Medical Officer Ramiro Ribeiro, the full analysis set showed an approximately 3.8-letter difference in best-corrected visual acuity between DURAVYU and aflibercept. The lower bound of the confidence interval was approximately 5.7 letters, exceeding the pre-specified non-inferiority margin.

Jay Duker, EyePoint’s president and CEO, said the company attributed the outcome largely to nine patients in the DURAVYU arm who lost more than 15 letters of vision for reasons the company said were unrelated to wet AMD. These cases included six patients with geographic atrophy, two with glaucoma and one following retinal detachment. The company said no patients in the aflibercept control arm experienced a greater-than-15-letter loss from non-wet AMD causes.

When those nine patients were excluded in an ad hoc analysis, DURAVYU demonstrated a 2.4-letter difference versus aflibercept and met the non-inferiority threshold, according to the company. Ribeiro said the lower bound of the confidence interval in that analysis was approximately four letters.

EyePoint said the nine patients had good anatomic control of wet AMD and that supplemental treatment did not improve vision in those who received it. The company also said preliminary analyses did not indicate that adverse events, supplementation criteria or DURAVYU-induced safety issues caused the primary endpoint result.

Secondary Measures Showed Reduced Treatment Burden

While the primary endpoint was not achieved in the full population, EyePoint reported favorable results on several secondary measures. DURAVYU reduced treatment burden by 42% through week 56 compared with aflibercept, which the company said was statistically superior to standard care.

• 76% of DURAVYU-treated eyes were supplement-free through week 32, or six months after the first DURAVYU administration.
• 54% were supplement-free through the end of the first year.
• Nearly 80% received zero or one supplemental injection through week 56.
• Approximately 90% of DURAVYU-treated eyes were stable with two or fewer supplemental injections through week 56.

The company also reported close anatomic control between treatment groups. The difference in central subfield thickness at week 56 was four microns. In a subgroup of patients who did not require supplemental treatment, DURAVYU was non-inferior to aflibercept, with a 1.8-letter difference in visual acuity, according to EyePoint.

Safety Findings and Next Steps

EyePoint characterized the repeat-dose safety profile as favorable. The company reported no cases of insert migration into the anterior chamber, anterior chamber opacities, free-floating drug particles, retinal vasculitis or severe intraocular inflammation. There was one case of intraocular inflammation in each study arm, and the DURAVYU case improved after two weeks of topical treatment.

Rates of retinal detachment and endophthalmitis were each below 1% in both arms, EyePoint said. Floaters occurred at roughly 2.5 times the rate seen with aflibercept, although the company said all reported cases were mild or moderate, required no treatment and did not affect vision. Discontinuation rates were approximately 6% in each arm.

Duker said EyePoint remains confident in its second Phase III wet AMD trial, LUCIA, which has a similar design. LUGANO enrolled patients exclusively in the U.S., while LUCIA enrolled approximately 80% of patients in the U.S. and 20% outside the country, Ribeiro said. EyePoint expects LUCIA data in the fourth quarter of this year.

If LUCIA is positive, Duker said the company expects to discuss its wet AMD data package with the FDA and hopes to submit a new drug application in the first half of 2027. He said prior trial data, including the DAVIO 2 study, could provide supporting safety evidence. EyePoint also said topline results from its two pivotal diabetic macular edema trials, COMO and CAPRI, are expected in the fourth quarter of 2027.

About Eyepoint Pharmaceuticals (NASDAQ:EYPT)

Eyepoint Pharmaceuticals, Inc is a biopharmaceutical company focused on the development and commercialization of therapies for the treatment of ocular diseases. The company's proprietary platform centers on sustained-release formulations designed to improve drug delivery to the posterior segment of the eye, addressing conditions that often require repeated intravitreal injections or intensive topical regimens. Eyepoint's commercial strategy combines in-house sales and marketing capabilities with targeted partnerships to bring its therapies to ophthalmologists and retina specialists across the United States.

Eyepoint's lead products include YUTIQ, a fluocinolone acetonide intravitreal implant indicated for the prevention of relapse in non-infectious uveitis affecting the posterior segment of the eye, and DEXYCU, a dexamethasone intraocular suspension approved for postoperative inflammation following ocular surgery.

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