Eyepoint, Inc. recently announced topline results from the pivotal phase 3 LUGANO trial for DURAVYU (EYP-1901; vorolanib intravitreal insert) for the treatment of wet age-related macular degeneration (AMD).
First up: DURAVYU.
What it is: This investigational sustained delivery therapy is under clinical development as a small-molecule, selective, and potent pan-vascular endothelial growth factor (VEGF) receptor inhibitor.
Its composition: encompasses a biodegradable formulation of two key components:
- DURASERT E, an injectable, sustained-delivery system for therapeutics
- See here for a rundown on the proprietary technology
- Vorolanib (a tyrosine kinase inhibitor [TKI])
- Has the potential to provide a mechanism of action (MOA) for treating VEGF-mediated retinal diseases.
And its delivery?
DURAVYU is administered via a single-dose—twice-yearly; at least every 6 months—intravitreal (IVT) injection being evaluated for two indications:
- Wet AMD (our focus for today)
- Diabetic macular edema (DME)
Didn’t I recently hear about Eyepoint?
Indeed. The company announced in March that the first patients had been dosed in two phase 3 global clinical trials (COMO [NCT07449936] and CAPRI [NCT07449923]).
However, those trials were for that second investigational indication: DME.
Ah gotcha. So tell me more about this wet AMD program then.
To start: The phase 1 and 2 DAVIO and DAVIO 2 trials demonstrated statistically positive and clinically meaningful results compared to on-label aflibercept.
Building on this success, the phase 3 pivotal portion (LUGANO [NCT06668064] and LUCIA [NCT06683742]) is evaluating every 6-month dosing of DURAVYU over 2 years, enabling the potential to support a competitive label and advantage for DURAVYU.
- The reason: To potentially provide a meaningful reduction in the treatment burden associated with wet AMD management, as the current standard of care is dosed—on average—every 2 months in the United States under a treat-and-extend protocol.
Back to these phase 3 trials.
Enrollment is complete in LUGANO and LUCIA, with over 900 patients randomized across the identical, randomized, double-masked, aflibercept controlled, non-inferiority studies.
Their purpose: to assess the efficacy and safety of DURAVYU among treatment-naive and -experienced patients with active wet AMD.
Note: The topline data covered below is based on the LUGANO cohort only.
What are the main outcome measures?
The primary endpoint is non-inferiority in the average change in best corrected visual acuity (BCVA) at Weeks 52 and 56 compared to baseline.
Secondary endpoints include:
- Safety
- Reduction in treatment burden
- Percentage of eyes free of supplemental aflibercept injections
- Anatomical results as measured by optical coherence tomography (OCT)
Moving on to the topline data from Lugano…
While the primary endpoint was not achieved in the full dataset, DURAVYU was found to be non-inferior to on-label aflibercept (nominal p-value = 0.0096) in an ad hoc analysis that excluded a 4% asymmetric cohort (9 of 211 patients) who experienced vision loss (≥15 letters) unrelated to wet AMD.
- Conversely: No patients experienced vision loss (≥15 letters) unrelated to wet AMD in the aflibercept control arm.
Anything else to note on this?
In prior reported similar scale phase 3 trials: Approximately 3-5% of aflibercept patients lost ≥15 letters.
This indicated a meaningful overperformance of the on-label aflibercept control group in LUGANO that also contributed to the primary endpoint performance.
Got it. Now dig deeper into the secondary endpoint data.
DURAVYU was reported to be safe and well tolerated with repeat dosing in patients.
No differences were observed in cataracts, elevated intraocular pressure (IOP), or intraocular inflammation (IOI) between the study and control groups.
Moreover: There were also no reported occurrences of:
- Insert migration
- Anterior chamber opacities
- Free-floating drug particles
- Retinal vasculitis
- Severe IOI
Was there a reduction in treatment burden?
Indeed. The company reported a 42% reduction in treatment burden, achieving superiority versus on-label aflibercept (nominal p-value<0.0001) compared to a maximum possible reduction of 60%.
The significance: This reduction translates to two fewer injections on average in DURAVYU patients versus on-label aflibercept up to Week 56.
And how many patients needed supplemental injections in the DURAVYA arm?
- By Week 32:
- 76% of patients were supplement-free
- 94% of patients received zero or one supplement
- By Week 56:
- 54% of patients were supplement-free
- 79% of patients received zero or one supplement
Further: A pre-specified analysis of change in BCVA from baseline to average Week 52/56 in supplement-free patients showed that DURAVYU was non-inferior (nominal p-value= 0.0035) compared to on-label aflibercept.
Anything else?
DURAVYU also demonstrated strong anatomic control with a mean difference of 4 μm versus on-label aflibercept control in central subfield thickness (CST) at Week 56.
The 54% of DURAVYU eyes that were supplement free up to Week 56 showed only a 3-μm difference in CST compared to the on-label aflibercept control
So what did EyePoint have to say about this data?
President and CEO Jay S. Duker, MD, noted that, 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 DURAVYU as a new potential therapeutic option for wet AMD.”
Chief Medical Officer Ramiro Ribeiro, MD, PhD, also highlighted DURAVYU’s durable efficacy in maintaining a stable retinal anatomy through Week 56, which avoided “the sawtooth pattern commonly seen with intermittent anti-VEGF therapy.”
- The significance: This data showcased the “potential for repeat dosing of a tyrosine kinase inhibitor (TKI), a capability unique to our clinical program, coupled with a favorable safety profile.” he added.
And when can we expect further updates from this program?
Eyepoint is still currently on track to report topline data from the second phase 3 LUCIA trial in Q4 2026.
And on a regulatory note: The company anticipates potentially filing a New Drug Application (NDA) for DURAVYU for wet AMD by H1 2027.
… and beyond that? How about for its DME indication?
As we mentioned, the pivotal phase 3 COMO and CAPRI clinical trials for DURAVYU in DME have completed enrollment and officially kicked off patient dosing earlier this year.
- Topline data for both trials is anticipated in Q4 2027.
Also worth noting: In the more immediate future, EyePoint plans to present additional details on the LUGANO dataset— including subgroup analyses—at major retina conferences in the coming months, beginning at the Retina Society 59th Annual Scientific Meeting in September (23-26).