Eyepoint Pharmaceuticals (NASDAQ:EYPT) reported that its Phase III LUCIA trial of DURAVYU in wet age-related macular degeneration did not meet its primary non-inferiority endpoint against aflibercept, despite showing visual improvement, reduced treatment burden and what the company described as strong anatomic control.
Jay S. Duker, EyePoint’s president and chief executive officer, said the company was “deeply disappointed” by the result. The randomized, double-masked trial enrolled 475 patients with active wet AMD, including both previously treated and treatment-naïve patients. Participants were randomized one-to-one to receive DURAVYU 2.7 mg every six months or on-label 2 mg aflibercept every two months after a loading phase.
The study’s primary endpoint was the mean change in best-corrected visual acuity from baseline, measured as a blend of results at weeks 52 and 56. The trial used a non-inferiority margin of minus 4.5 letters.
Primary Endpoint Missed Despite Visual Gains
At the end of the trial, patients receiving DURAVYU gained an average of 2.5 letters in best-corrected visual acuity. However, the difference versus the aflibercept control arm was minus 3.7 letters, which was outside the study’s non-inferiority margin, according to Duker.
“LUCIA did not meet the primary endpoint of mean change in best-corrected visual acuity despite visual improvements,” Duker said. The company said it will conduct additional analyses of the LUCIA data, as well as data from its other wet AMD Phase III trial, LUGANO, to determine next steps for DURAVYU in wet AMD.
DURAVYU is a sustained-release tyrosine kinase inhibitor, or TKI, delivered through a standard intravitreal injection. EyePoint said the treatment was designed to provide VEGF receptor blockade, anti-inflammatory IL-6/JAK1 activity and potential anti-fibrotic benefits related to PDGF.
Reduced Injection Burden and Anatomic Results
EyePoint highlighted a reduction in treatment burden among DURAVYU-treated patients. After the loading phase, patients in the DURAVYU arm received an average of 3.3 injections, including two DURAVYU doses and 1.3 supplemental injections. Patients in the aflibercept arm received an average of 5.3 injections after loading, representing a 38% reduction in treatment burden, according to the company.
Through week 32, approximately six months after the first DURAVYU dose, 70% of DURAVYU patients did not require supplemental aflibercept injections. By the primary endpoint, 52% remained supplement-free, while 71% received zero or one supplemental injection.
The company also reported an approximately 16-micron difference in optical coherence tomography measurements between DURAVYU and aflibercept at the end of LUCIA. Duker said that difference would likely not be considered clinically significant in practice. In pooled data from LUCIA and LUGANO, EyePoint reported a 40% reduction in treatment burden and an approximately 10-micron difference in anatomic results.
Safety Findings and DME Focus
EyePoint said no cases of insert migration into the anterior chamber, anterior chamber opacities, free-floating drug particles or retinal vasculitis were reported in LUCIA. Intraocular inflammation and endophthalmitis occurred in less than 1% of patients in both study arms. Vitreous floaters were more common in the DURAVYU arm, although the company said most cases were mild.
Patient discontinuation rates were approximately 8% in both trial arms, and none of the discontinuations were attributed to the study or treatment, according to the company.
Following the LUCIA outcome, EyePoint said it is now focused on its Phase III diabetic macular edema, or DME, program. Its COMO and CAPRI trials are identical Phase III studies evaluating DURAVYU in DME. More than 550 patients have been enrolled across the two trials, with first patients dosed in February and full enrollment completed in July.
The company expects topline data from COMO and CAPRI in the fourth quarter of 2027. Duker said EyePoint believes DURAVYU’s potential anti-inflammatory properties and results from the Phase II VERONA DME trial support continued development in the indication.
“We plan on continuing to review the data from LUGANO and LUCIA to determine the appropriate next steps for DURAVYU in wet AMD,” Duker said, while reiterating that the company remains focused on advancing the DME Phase III program.
About Eyepoint Pharmaceuticals (NASDAQ:EYPT)
EyePoint Pharmaceuticals, Inc is a biopharmaceutical company focused on developing and commercializing therapies for serious eye diseases. The company specializes in sustained-release drug delivery technologies designed to provide extended treatment in the eye and potentially reduce the frequency of injections or other interventions.
EyePoint’s commercial products include YUTIQ, an intravitreal implant that delivers fluocinolone acetonide for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye, and DEXYCU, an intraocular suspension of dexamethasone used to treat postoperative inflammation following ocular surgery.
