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Positive topline data reported in EyePoint's phase 2 wet AMD trial

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EyePoint Pharmaceuticals, Inc. announced positive topline data from the phase 2 DAVIO 2 trial on EYP-1901 for the treatment of wet age-related macular degeneration.

Refresh me on EYP-1901.

EYP-1901 is an investigational, selective and potent pan-vascular endothelial growth factor (VEGF) receptor inhibitor for retinal disease that incorporates a bioerodible formulation of EyePoint’s proprietary Durasert delivery technology (Durasert E; more on that below) with vorolanib (a tyrosine kinase inhibitor [TKI]).

And this Durasert technology?

The Durasert technology is designed as a miniaturized, injectable, sustained-delivery system that can provide a continuous, stable release of therapeutics within the eye over the course of weeks to months, or even years.

Two versions of the platform are available: Durasert E (bioerodible, used for EYP-1901) and Durasert (non-erodible). Click here for further details.

Gotcha. So EYP-1901 is being evaluated for …

The small-molecule, anti-vascular endothelial growth factor (VEGF) therapy is in clinical development as a twice-yearly, single-dose intravitreal injection for the three ocular conditions:

  • Wet AMD → 6-month maintenance therapy
  • Non-proliferative diabetic retinopathy (NPDR) → 9-month maintenance therapy (see here for phase 2 trial details)
  • Diabetic macular edema (DME) → 6-month maintenance therapy

Let’s talk clinical data now.

Sure, but before we get to this DAVIO 2 data, we'll need to know what happened in the phase 1 DAVIO trial (NCT04747197).

The prospective, multicenter, dose-escalation, open-label study evaluated EYP-1901 at three dose levels (440 µg, 2060 µg and 3090 µg) as a possible six-month treatment for previously-treated wet AMD.

EYP-1910 demonstrated a favorable safety and efficacy profile at 12 months, with no dose-limiting toxicities, ocular serious adverse events (SAEs), or drug-related systemic SAEs, and the potential to maintain the majority of patients for up to 6 months with no supplemental anti-VEGF therapy.

Alrighty, I’m ready for phase 2.

The phase 2 DAVIO 2 trial (NCT05381948) is a multicenter, prospective, randomized, double-masked, and parallel study comparing the efficacy of EYP-1901 for wet AMD at two single doses—2060 µg (2 mg) and 3090 µg (3 mg)—against aflibercept (2 mg) injected every 8 weeks.

To note, the new data is based on 6-month (up to 32 weeks) data from the study.

And the patients?

A total of 160 wet AMD patients (ages 50+) were enrolled with the following inclusion criteria:

  • Previously treated with at least two anti-VEGF intravitreal injections for wet AMD within 6 months prior to screening.
  • Best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) score of 35 letters (20/200 Snellen equivalent) to 85 letters (20/20 Snellen equivalent) in the study eye at screening and Day 1.

See here for exclusion criteria.

What was measured?

Primary outcomes included the average BCVA at Week 28 and Week 32.

Secondary outcomes included:

  • Change in BCVA at baseline and Week 56
  • Mean change in central retinal thickness (CRT) on optical coherence tomography (OCT) at baseline and Week 56.
  • Number of rescue injections at Week 56

And the findings?

Per EyePoint, the trial met its primary endpoint, “with both EYP-1901 doses demonstrating statistical non-inferiority change in (BCVA) compared to aflibercept control.”

Both 2 mg and 3 mg doses were only -0.3 and -0.4 letters different, respectively, when compared to aflibercept, and a 89% (2 mg) and 85% (3 mg) reduction in treatment burden were noted.

Any adverse events?

Nope. In fact, a favorable safety profile and no related ocular or systemic serious adverse events (SAEs) were reported.

What about secondary outcomes?

Both doses achieved secondary endpoints with the following stats:

  • Over 80% reduction in treatment burden
  • 65% (2 mg) and 64% (3 mg) of EYP-1910 eyes went supplement-free for up to 6 months
  • Over 80% received zero or just one supplement up to 6 months

The company also reported a “strong anatomical control with both EYP-1901 cohorts” as measured by optical coherence tomography (OCT).

Significance?

Per EyePoint President and CEO Jay S. Duker, MD, PhD, the DAVIO 2 trial was designed to support the initiation of phase 3 trials (based on FDA feedback from a Type C meeting with the agency in 2022).

“The 32-week topline DAVIO 2 data strongly supports our planned phase 3 non-inferiority design, consistent with the FDA’s recent guidance for wet AMD clinical trials,” Dr. Duker stated.

So what’s next?

The company is planning to continue phase 3 trial plans with the FDA while also preparing to launch its first pivotal trial for wet AMD in the second half of 2024, according to Dr. Duker.