EyePoint Pharmaceuticals, Inc. reported new topline interim data from its phase 2 PAVIA study assessing its newly-named DURAVYU, an investigational candidate for the treatment of non-proliferative diabetic retinopathy (NPDR).
The results were a mixed bag of positive and negative data—read below for our rundown.
Let’s start with DURAVYU.
DURAVYU (vorolanib intravitreal insert)—formerly named EYP-1901, in case it doesn’t sound familiar to you— is a small-molecule, selective and potent pan-vascular endothelial growth factor (VEGF) receptor inhibitor for the treatment of retinal disease.
What it does: incorporates a bioerodible formulation of EyePoint’s proprietary DURASERT delivery technology (DURASERT E; more on that later) with vorolanib (a tyrosine kinase inhibitor [TKI]).
- Refresh: Vorolanib can provide potent and selective pan-VEGF receptor inhibition by blocking downstream signaling of all three VEGF receptors
What’s it being developed for?
The therapeutic is in clinical development as a twice-yearly, single-dose intravitreal injection for:
- NPDR → 9-month maintenance therapy
- Wet age-related macular degeneration (AMD) → 6-month maintenance therapy
- Diabetic macular edema (DME) → 6-month maintenance therapy
Gotcha. Now explain DURASERT E.
EyePoint’s DURASERT technology is a miniaturized, injectable, sustained-delivery system designed to provide a continuous, stable release of therapeutics within the eye over an extended period of time (weeks, months, and potentially even years).
Moving on to this phase 2 study.
The multicenter, prospective, double-masked, parallel PAVIA phase 2 study (NCT05383209) is assessing the ocular efficacy and safety of EYP-1901 (DURAVYU) as a single intravitreal injection compared to sham.
Study duration: 12 months
The participants: 77 participants (aged 18+) with the following criteria:
- Hemoglobina A1c ≤12%
- Best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) score in study eye of ≥69 letters (approximate Snellen equivalent of 20/40 or better)
And the dosings?
Patients are being randomized to receive either of the following single injected doses every 8 weeks:
- DURAVYU 2,060 µg (2.06 mg; rounded to 2 mg)
- DURAVYU 3,090 µg (3.09 mg; rounded to 3 mg)
- Sham
What’s being measured?
Primary outcome: patients improving ≥2 steps in the Diabetic Retinopathy Severity Scale (DRSS) score in each DURAVYU dose group vs sham group, measured at baseline and Week 36.
Secondary outcomes:
- ≥2 steps in the DRSS score for each DURAVYU dosage vs sham
- Measured at baseline, Week 24, and Week 48
- Patients who developed vision-threatening complication due to DR
- Measured at Weeks 24, 36, and 48
- Rates of ocular and nonocular treatment-emergent adverse events (TEAEs) in the study and fellow eyes
- Measured at Weeks 24, 36, and 48
Didn’t the company already report phase 2 data?
Yes… back in December 2023. However, that was for wet AMD in the DAVIO-2 trial (NCT05381948)So: same drug, different indication. See here for the full rundown.
At last… this new data.
Let’s get the bad news out of the way first: The trial did not meet its primary endpoint.
Despite this, EyePoint’s CEO Jay Duker, MD, noted that the data indicated “DURAVYU continues to be well-tolerated and appears to reduce rates of NPDR progression at 9 months.”
Give me some stats.
At 9 months (36 weeks):
- 86% (3 mg dosed) and 80% (2 mg dosed) of patients demonstrated stable or improved disease vs only 70% of patients in the control arm
In regards to ≥2-step in the DRSS score:
- None of the 3 mg patients and 5% of 2 mg patients worsened vs 10% for control
- 5% of the 3 mg patients and none of the 2 mg achieved improvement vs 5% for control
Any adverse events noted?
No TEAEs (ocular or systemic) were reported. In fact, DURAVYU demonstrated a continued favorable safety and tolerability profile.
Plus: EyePoint noted no occurrences of endophthalmitis or retinal vasculitis.
Gotcha. So what are the company’s next steps?
Dr. Duker noted that EyePoint plans to report full 12-month data on DURAVYU for NPDR following a full review.
Further, the company is also reportedly still on track to reach its additional milestones for the candidate:
- Expected initiation of the phase 3 LUGANO pivotal trial
- Indication: wet AMD
- Timeframe: H2 2024
- Expected initiation of the second global phase 3 LUCIA trial
- Indication: wet AMD
- Timeframe: following H2 2024
- Topline data from the phase 2 VERONE trial
- Indication: DME
- Timeframe: Expected Q1 2025
And for this PAVIA trial, when can we expect that 12-month data?
Likely not until 2025, as the study is slated to conclude in August 2025.