Shares of EyePoint Pharmaceuticals fell on Thursday after the ophthalmic drug developer disclosed that its DURAVYU implant failed to meet its primary endpoint in the Phase III LUGANO trial for neovascular age-related macular degeneration.
The stock dropped $0.22, or 4.61%, to $4.14 at the time of reporting, continuing a steep decline that has erased roughly three-quarters of its value year-to-date. The company's market capitalization stood at approximately $356 million.
Jay Duker, EyePoint's chief executive, did not shy away from the result. "The elephant in the room, obviously, is we missed the primary endpoint," he said during the company's presentation at the 12th Annual Cantor Fitzgerald Global Healthcare Conference.
LUGANO enrolled 432 patients and compared DURAVYU, a vorolanib-based ophthalmic implant, against on-label aflibercept (Eylea) sold by Regeneron. The trial's primary goal was to demonstrate non-inferiority in visual acuity change from baseline to weeks 50 through 56, using a prespecified margin of 4.5 letters. The DURAVYU arm did not clear that bar.
However, a subset of the data offered some reassurance. Four percent of patients in the DURAVYU group lost 15 or more letters of vision, compared with just 0.5% in the Eylea arm. Nine patients in the DURAVYU arm experienced these vision losses, including cases tied to retinal detachment and geographic atrophy. When those nine patients were excluded, the visual acuity difference between arms narrowed to 2.4 letters, which would have met the non-inferiority threshold. Random simulations across both arms produced non-inferiority differences ranging from 1.3 to 2.0 letters.
Duker and his colleagues placed emphasis on secondary measures of treatment burden and anatomical control. After the initial loading phase, DURAVYU reduced treatment burden by 42%, translating to roughly two fewer injections per year compared with Eylea. At six months, 76% of patients were supplement-free; at one year, 54% were supplement-free and nearly 80% required zero or one supplemental injection over the course of the year. Nearly 90% maintained disease control with four or fewer total injections annually, including DURAVYU and supplement doses. Among supplement-free patients, the visual acuity difference versus supplement-free Eylea patients was just 1.4 letters.
Geographic atrophy progression was slower with DURAVYU than with historical benchmarks. The DURAVYU arm recorded a GA progression rate of 1.7 square millimeters per year, below the 2.0-to-2.2 square-millimeter range seen historically; the fellow eye progressed at 1.6 square millimeters per year. By year-end, GA was present in 29% of Eylea patients versus 24% in the DURAVYU group.
Safety observations included floaters occurring at about 2.5 times the rate of the control arm, described as mild to moderate, and one case of intraocular inflammation treated with a topical steroid.
EyePoint confirmed it will proceed with the LUCIA trial, which will enroll 475 patients — 43 more than LUGANO — under an otherwise identical design and including a pre-specified sensitivity analysis. Top-line data from LUCIA is expected in the fourth quarter of 2024, no earlier than late October and potentially into early November. The full dataset will be presented publicly at the FLORetina meeting in the first week of December.
The company also highlighted earlier Phase II DME data from the VERONA trial, which showed a 4-to-5 letter vision improvement and a 40-to-50 micron dryness advantage at week 4 versus Eylea. Other presentations are scheduled for the Retina Society meeting later in September, followed by sessions at the American Academy of Ophthalmology and EURETINA in October.
With the diabetic macular edema market valued at roughly $3 billion, investors are watching to see whether EyePoint can convert its treatment-burden narrative into regulatory traction at the next catalyst.
