EyePoint, a Boston-area biotechnology company, lost nearly a billion dollars in market value Monday after its main drug failed to hit the central goal of a key clinical trial.
Titled LUGANO, the trial enrolled roughly 400 people with the less common “wet” form of age-related macular degeneration, meaning they have impaired vision because of abnormal, fluid-leaking blood vessels in their eyes. They received inside-the-eye injections of either “aflibercept,” the active ingredient in Regeneron Pharmaceuticals’ blockbuster medicine Eylea, or EyePoint’s drug, which the company has branded as Durayvu.
Researchers then evaluated these participants for a little over a year, with a particular focus on any changes in average “best-corrected visual acuity” — a measure of how clearly a person, when outfitted with optimal prescription lenses, can read the kind of standard eye chart found in an optometrist office. EyePoint has now revealed that, on that measure, across the trial’s full dataset, its drug didn’t prove “non-inferior” to aflibercept.
The company largely blamed the failure on an “asymmetric cohort” of nine patients in the Durayvu-treated group, who had vision loss — or a dropoff of at least 15 letters on the eye exam — that was “unrelated to wet AMD.” According to EyePoint, an after-the-fact analysis found the drug would have achieved non-inferiority had that group been excluded.
Additionally, no patients in the aflibercept group experienced vision loss that was on that scale and unrelated to wet AMD. EyePoint said this indicates “meaningful overperformance” in the control arm, since other, similarly designed studies have shown around 3-5% of patients on aflibercept losing 15 or more letters when tested.
Those issues aside, EyePoint maintained the trial produced “compelling” data that “represent a meaningful improvement to current wet AMD standard of care.” The company highlighted how Durayvu demonstrated “favorable” safety, reduced the burden of treatment and allowed three-fourths of patients to go about eight months without supplemental injections of “anti-VEGF” therapies — a class of drugs that includes Eylea as well as Lucentis, Vabysmo and Beovu.
“While the primary endpoint result for the full dataset was unexpected, the consistently positive results from the pre-specified secondary endpoints and the ad hoc analysis on the primary endpoint present a compelling case for [our drug] as a new potential therapeutic option for wet AMD,” Jay Duker, EyePoint’s CEO, said in a statement.
Duker added that his company may file for Food and Drug Administration approval in the first half of next year, depending on how a second late-stage trial, “LUCIA,” shakes out. Results from that experiment should come sometime between October and the end of December.
Investors, meanwhile, appear to have lost confidence in EyePoint and its program, as shares were down 70% by mid-morning Monday.
Lisa Walter, an analyst at RBC Capital Markets, wrote in a note to clients that the LUCIA results “will be needed to paint a clearer picture” of EyePoint’s future in wet AMD. Yet, even if the study is successful, “we think it will be more challenging” for the FDA to approve Durayvu without two positive non-inferior trials.
The primary endpoint miss is a “genuine overhang,” Mizuho Securities analyst Graig Suvannavejh wrote in his own note. LUCIA is now the “swing factor,” as a “clean” win would “substantially de-risk” the story and approval plans around Durayvu, whereas a second miss would be “far more problematic.”
To Stifel analyst Annabel Samimy, the findings from LUGANO, while “tricky,” still offer reasons to be optimistic about Durayvu.
“Optically, this imbalance is disappointing given the competitive landscape, but it is clear to us that Duravyu is having clinical benefit and has the potential to extend treatment intervals and reduce injection frequency by a significant amount in a maintenance setting,” Samimy wrote.
