Eyepoint, Inc. released topline results from the phase 3 LUCIA study evaluating DURAVYU (EYP-1901; vorolanib intravitreal insert) for the treatment of wet age-related macular degeneration (AMD).
Hold up — didn’t the company just report phase 3 data for wet AMD?
Yes … just a couple months ago, in fact (our coverage here).
However, that data readout was based on the LUGANO trial (NCT06668064)—the first phase 3 study evaluating DURAVYU for its wet AMD indication.
Gotcha. Well, before we talk data, let’s get a refresher on DURAVYU.
What it is: DURAVYU (vorolanib intravitreal insert) is a small-molecule, selective, and potent pan-vascular endothelial growth factor (VEGF) receptor inhibitor.
- Its clinical status: The therapy is currently under clinical investigation for two potential retinal disease indications: wet AMD and diabetic macular edema (DME).
- To note: Phase 3 dosing is currently underway for its DME indication.
And how does it work?
By pairing vorolanib, a selective tyrosine kinase inhibitor (TKI), with EyePoint’s proprietary, bioerodible Durasert E delivery technology, which is designed to release drugs for at least 6 months.
- According to EyePoint, vorolanib acts intracellularly to inhibit all VEGF receptors and PDGFR, while also suppressing inflammation through inhibition of interleukin 6 (IL-6)/JAK1 signaling.
As for its delivery: DURAVYU is administered via a single-dose, intravitreal (IVT) injection at least every 6 months.
Alrighty, now to its clinical performance thus far.
Before we talk phase 3 data, we’ve got to call out the prior clinical evaluations conducted on DURAVYU: the phase 1 and 2 DAVIO and DAVIO 2 trials.
- In those studies, DURAVYU demonstrated statistically positive and clinically meaningful results compared to on-label aflibercept.
And in this phase 3 wet AMD program?
The phase 3 pivotal portion—LUGANO (NCT06668064) and LUCIA (NCT06683742)—is evaluating the efficacy and safety of DURAVYU when administered:
- As an every-6-month dosing injection
- Among 900+ treatment-naive and -experienced patients with active wet AMD
- Over a 2-year period
The potential: to support a competitive label and advantage for DURAVYU. See here for why.
Before we look at the LUCIA data, recap the LUGANO findings.
It was a mixed bag, to say the least. The study fell short of meeting its primary endpoint (non-inferiority in the average change in best corrected visual acuity [BCVA] at Weeks 52 and 56 compared to baseline).
But in an ad hoc analysis: DURAVYU was found to be non-inferior to on-label aflibercept (nominal p-value = 0.0096) after the exclusion of a 4% asymmetric cohort involving patients who experienced vision loss (≥15 letters) unrelated to wet AMD.
- See here for more findings from this data readout, including its secondary outcomes.
Now to this new reporting.
To note: Both trials have the same primary and secondary outcomes.
And in this latest data readout, topline results from the LUCIA trial followed a similar trend to LUGANO: Despite demonstrating visual improvement, “DURAVYU did not achieve the primary endpoint.”
How about secondary endpoints?
Consistent with its performance in the LUGANO trial, DURAVYU achieved these.
Specifically, the therapy demonstrated “a continued favorable safety profile with redosing” along with:
- A meaningful reduction (38%) in treatment burden (nominal p-value <0.0001)
- Durability (as demonstrated by supplement-free rates)
- 52% of eyes were supplement-free
- 71% of eyes received zero or one supplement (up to week 56)
- Strong anatomical control at week 56
Noted. So what’s next for this indication?
EyePoint plans to conduct additional analyses from the LUCIA trial as well as pooled phase 3 datasets to “further assess next steps” for DURAVYU’s potential wet AMD indication.
Interesting … any other feedback from the company?
While the wet AMD phase 3 program fell short in meeting its primary goals, President and CEO Jay S. Duker, MD, noted that the studies actually supported DURAVYU’s therapeutic potential for its second investigational indication: DME.
The reasoning: Both LUGANO and LUCIA “demonstrated DURAVYU’s ability to control fluid and reduce the treatment burden for patients with wet AMD.”
And this could be beneficial for DME patients?
That’s the thinking. Also keep in mind that DURAVYU has performed far more favorably in its DME clinical evaluations.
Case in point: The phase 2 VERONA trial met both its primary and secondary endpoints.
- In fact, Dr. Duker referenced DURAVYU’s performance in the VERONA trial as supporting the therapy’s position to “potentially deliver stable vision with fewer injections” than the current standard of care for DME.
Tell me more.
As a follow-up to its wet AMD data readout, the company also announced a new strategic prioritization (alignment) that will “reduce operating expenses” and allow its resources to focus on its DME program.
Specifically: EyePoint’s Board of Directors have approved a plan to:
- cut its employee workforce by an estimated 53%
- conclude its phase 3 wet AMD trials early (without fully completing the second year for each)
How much is this supposed to save on costs?
The expectation: an estimated annualized savings of around $30 million.
Wow. Okay, so what’s the latest for that clinical program?
The pivotal phase 3 COMO (NCT07449936) and CAPRI (NCT07449923) clinical trials have completed enrollment and officially kicked off patient dosing earlier this year.
See here for details on the studies’ participants, setup, and outcome measures.
And what’s the next milestone target date?
With a renewed focus on its DME indication, EyePoint is planning for a pivotal phase 3 data readout from both trials in Q4 2027.