EyePoint shares plummeted more than 84% Monday morning after the company announced that its phase 3 Lucia trial—its final holdout in wet age-related macular degeneration (wet AMD) following a previous miss in August—failed to meet its primary endpoint.
Lucia tested EyePoint’s drug-device combo Duravyu against the current standard of care for wet AMD, Regeneron’s blockbuster Eylea, in hopes of demonstrating equal treatment benefit with fewer ocular injections.
But in new topline results, EyePoint disclosed that its tyrosine kinase inhibitor performed worse than Eylea in the primary endpoint of improved best-corrected visual acuity (BCVA)—with the study in turn failing to meet its non-inferiority goal.
The results could mark the final straw for Duravyu’s wAMD program. In an attempt to sooth investors and preserve capital, EyePoint said it plans to reduce its workforce by 53% and cut both Lucia and its companion phase 3 Lugano short without completing their planned second year.
The rapid restructuring is expected to save the drugmaker $30 million that it can reallocate to its diabetic macular edema (DME) pipeline, which EyePoint has named its new priority.
Just two months ago, Lucia was a beacon of hope after the twin Lugano trial miss was attributed to “bad luck." Unusual rates of non-wet AMD vision loss were believed to confound the trial and keep it from meeting its primary endpoint.
Jefferies analysts were inclined to see the “bad luck explanation as legit,” leaving room for hope that Lucia would right the ship. “LUCIA feels like a coin flip but we lean pos given how close LUGANO was to a win,” the Jefferies team said at the time.
But in the topline readout, Duravyu improved BVCA by only 2.5 letters over 52 weeks to Eylea’s 6-letter improvement—a 3.7 difference which fell outside of the non-inferiority margin.
“I want to reiterate that we continue to believe TKIs have the potential to be the next phase of retinal disease innovation. Today’s data reinforces our fundamental conviction in Duravyu,” said EyePoint CEO Jay Duker, M.D., on a Monday conference call discussing the results.
The aim of Duravyu is to provide vision benefits equal to traditional anti-VEGF treatments but with more durable delivery. Duravyu’s ocular implant delivers a sustained release of the drug vorolanib for at least six months, potentially giving patients more continuous relief with fewer interventions.
On the investor call, Duker emphasized Duravyu’s success across multiple secondary endpoints in Lucia, including a significant improvement in fluid control and a 38% decrease in number of injections, while safety data remained favorable.
He said EyePoint will also be doing additional analysis on the Lucia and Lugano trials to “assess the next steps for Duravyu as a potential treatment for wAMD.”
But DME will become the company’s new top priority. EyePoint finished enrolling the Como and Capri phase 3 trials testing Duravyu in that indication in July. Both are set to readout in the fourth quarter of 2027.
In an attempt to bolster investor confidence in the DME pipeline, Duker reviewed the data from Duravyu’s phase 2 DME win on the call. In the midstage trial, Duravyu sustained visual acuity, and more than 70% of patients on the drug remained supplement-free for six months. The drug also showed potential for a more rapid reduction in fluid and improvement in vision compared to Eylea—with benefits seen as early as week 4.
Based on the drug’s mechanism of action and the phase 2 findings, EyePoint is “confident that Duravyu is positioned well to deliver potentially earlier benefits with fewer injections versus the standard of care,” Duker said.
Eyepoint estimates it had $118 million in cash and equivalents as of Sept. 30. The pharma said it expects the majority of the workforce reduction to be done by end of year and finish in the fist half of 2027.
The reorganization is expected to cost the company roughly $9 million in severance and separation benefits, according to EyePoint.