EyePoint Pharmaceuticals, Inc. announced the dosing of its first patient in the phase 3 LUGANO clinical trial of DURAVYU (tyrosine kinase inhibitor; formerly known as EYP-1901) for the treatment of wet age-related macular degeneration (AMD).
First, a rundown on DURAVYU.
DURAVYU (vorolanib intravitreal insert) is a small-molecule, selective and potent pan-vascular endothelial growth factor (VEGF) receptor inhibitor in clinical investigation for the treatment of retinal disease.
What it does: Incorporates a bioerodible formulation of EyePoint’s proprietary DURASERT delivery technology (we’ll get to that in a moment) with vorolanib (a tyrosine kinase inhibitor [TKI]).
- To note: Vorolanib is known to provide potent and selective pan-VEGF receptor inhibition by blocking downstream signaling of all three VEGF receptors.
- And per EyePoint: It brings a potential new mechanism of action (MOA) for treating such VEGF-mediated retinal diseases as DME.
Two questions for you: First, can you explain that delivery technology?
Absolutely … EyePoint’s DURASERT technology is designed to be a miniaturized, injectable, sustained-delivery system that provides a continuous and stable release of therapeutics within the eye over an extended period of time (weeks, months, and potentially even years).
Its delivery mechanism: Via a standard, in-office, intravitreal (IVT) injection
- See how it’s utilized for other drugs, operating as DURASERT E (bioerodible) and DURASERT (non-erodible).
Gotcha. Next: What indications is DURAVYU in development for?
Three indications so far, where it’s delivered as a twice-yearly, single-dose IVTi injection:
- Wet AMD: 6-month maintenance therapy
- Diabetic macular edema (DME): 6-month maintenance therapy
- Latest clinical update: The phase 2 VERONA study is evaluating both the safety and efficacy of DURAVYU (study status: active but not currently recruiting, with topline data expected Q1 2025)
- Nonproliferative diabetic retinopathy (NPDR): 9-month maintenance therapy
- Latest clinical update (May 2024): While DURAVYU demonstrated a continued favorable safety profile and tolerability, it failed to meet its primary goal in the phase 2 PAVIA study
Now to this phase 3 trial.
The phase 3 LUGANO trial—as well as its twin LUCIA trial—is a global, randomized, double-masked, aflibercept-controlled study seeking to demonstrate the ability of DURAVYU to achieve similar visual outcomes as aflibercept while also reducing treatment burden in wet AMD patients.
- Participant info: 400 patients, including those previously treated and treatment-naïve
- Across 150+ clinical trial locations
- The design: Patients are being randomized to two arms to receive either:
- 2.7 mg DURAVYU
- Administered every 6 months
- Starting at Month 2 of the trial following three loading doses of aflibercept
- Administered every 6 months
- 2 mg aflibercept on-label (control)
- Administered every 8 weeks (qw8; ie: 2 months)
- 2.7 mg DURAVYU
- Study duration: 1 year
Note: EyePoint stated that LUGANO and LUCIA are “the only sustained-release wet AMD phase 3 trials evaluating re-dosing in both trials.”
Real quick: Why include both previously-treated and treatment-naïve patients?
The intent is to provide a more accurate representation of real-world patient populations as well as build on the success of previously reported wet AMD phase 2 data (more on that later), according to Ramiro Ribeiro, MD, PhD, EyePoint chief medical officer.
What’s being measured?
The primary endpoint is the difference in mean change in best-corrected visual acuity (BCVA) from Day 1 to Week 52 and Week 56 (blended) versus aflibercept.
Secondary endpoints include:
- Safety
- Reduction in treatment burden
- Percentage of supplement-free eyes
- Anatomical stability (as measured via optical coherence tomography [OCT])
And the significance of this LUGANO study?
The first patient dosing is considered “a significant milestone” for the company and its investigational candidate, according to EyePoint President and CEO Jay S. Duker, MD.
He added that both phase 3 trials were “designed for potential global regulatory and commercial success based on our alignment with the FDA, as they follow a proven non-inferiority approval pathway.”
So when is data expected from this?
Topline data is anticipated by Q1 2026, EyePoint reported.
And any update on that LUCIA trial?
The company expects to dose its first patient by the end of 2024.
Nice! And lastly, how has DURAVYU performed for wet AMD so far?
EyePoint previously released positive topline data from its phase 2 DAVIO 2 trial (NCT05381948) in December 2023, where DURAVYU in two doses was evaluated in 150 wet AMD patients (aged 50+).
The crux of those findings: The trial met its primary endpoint, with both doses demonstrating a statistical non-inferiority change in (BCVA) compared to aflibercept control and DURAVYU demonstrating a favorable safety profile.
- See here for more details.