EyePoint Pharmaceuticals Announces Positive Topline Data from the Phase 2 DAVIO 2 Trial of EYP-1901 in Wet AMD

In a phase 2 study, EyePoint Pharmaceuticals’ wet AMD drug candidate demonstrated noninferiority to Eylea—with a less frequent dosing regimen. EyePoint leadership said the sustained-release implant could represent a 'paradigm-altering maintenance treatment' for patients with wet AMD.

EyePoint announced positive topline results of its phase 2 DAVIO 2 trial of EYP-1901, an investigational sustained delivery maintenance treatment for wet age-related macular degeneration (AMD) combining vorolanib, a selective tyrosine kinase inhibitor, with bioerodible Durasert E. The clinical trial met its primary endpoint with both EYP-1901 doses demonstrating statistical noninferiority change in best corrected visual acuity (BCVA) compared to aflibercept control and a favorable safety profile with no EYP-1901-related ocular or systemic serious adverse events (SAEs). The trial also achieved key secondary endpoints with both EYP-1901 doses, including an over 80% reduction in treatment burden, nearly two-thirds of eyes supplement-free up to 6 months, and over 80% receiving only zero or one supplement up to 6 months. Additionally, there was strong anatomical control with both EYP-1901 cohorts as measured by optical coherence tomography (OCT), according to Eyepoint. 

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“We are incredibly pleased by these highly positive phase 2 results which underscore EYP-1901’s potential as a paradigm-altering maintenance treatment for patients with wet AMD, with a positive safety profile. Since EYP-1901 achieved statistical noninferiority to the aflibercept control in this trial, there is potential for meaningfully lower sized and lower cost pivotal phase 3 trials,” Jay S. Duker, MD, President and Chief Executive Officer of EyePoint Pharmaceuticals, said in a company news release. “I would like to thank the patients and the investigators who participated in the DAVIO 2 trial as well as our employees who helped advance us to this important milestone.”

"The DAVIO 2 clinical trial was designed to support the initiation of phase 3 clinical trials based on feedback received from the U.S. Food and Drug Administration (FDA) at a Type C meeting last year," Dr. Duker said. "The 32-week topline DAVIO 2 data strongly supports our planned phase 3 noninferiority design, consistent with the FDA’s recent guidance for wet AMD clinical trials. We look forward to continuing our dialogue regarding our phase 3 plans with the FDA as we prepare to initiate our first pivotal trial for wet AMD in the second half of 2024.”

DAVIO 2 topline interim results include:

• Both EYP-1901 doses (2mg and 3mg) achieved all primary and secondary endpoints.
• Statistical noninferiority in change in BCVA (at a confidence interval of 95%) compared to aflibercept control, at weeks 28 and weeks 32 combined. The 2mg and 3mg doses were -0.3 and -0.4 letters different, respectively, versus on-label aflibercept. The lower limit of the noninferiority margin is defined as a -4.5 letters by the FDA with 5 letters representing 1 line on the eye chart.
• Continued positive safety and tolerability profile with no EYP-1901-related ocular or systemic SAEs.
• 89% and 85% reduction in treatment burden, respectively, for the 2mg and 3mg EYP-1901 doses.
• 65% and 64% of eyes were supplement free up to 6 months, respectively, for the 2mg and 3mg doses of EYP-1901.
• Both EYP-1901 doses demonstrated strong anatomic control with OCT difference below 10 microns at week 32 compared to the aflibercept control.
• Patient discontinuation up to week 32 was low at 4%.

“Wet AMD is a prevalent and progressive lifetime disease. With frequent treatment, patients can maintain their visual acuity, but the unfortunate reality is that many patients end up undertreated due to the burden of dosing of the currently available, short-acting anti-VEGF therapies,” said Carl Regillo, MD, Chief of Retina Service at Wills Eye Hospital. “I am very encouraged by the data generated from both the Phase 1 DAVIO and Phase 2 DAVIO 2 trials with the latter showing essentially no difference in visual outcome at the blended 6-month endpoint from a single injection of EYP-1901 compared to on-label, bimonthly aflibercept injections. Based on the meaningful reduction in treatment burden and supplement-free rates observed, along with the consistently favorable safety profile, I believe that EYP-1901 could be a paradigm shift in how patients with wet AMD are treated.”

DAVIO 2 is a randomized, controlled phase 2 clinical trial of EYP-1901 in previously treated patients with wet AMD. Originally designed to enroll 144 patients, the trial enrolled 160 patients in total due to strong investigator and patient interest. All enrolled patients were previously treated with a standard-of-care anti-VEGF therapy and were randomly assigned to one of two doses of EYP-1901 (approximately 2 mg or 3 mg) or an aflibercept control. EYP-1901 is delivered with a single intravitreal injection in the physician's office, similar to current FDA approved anti-VEGF treatments. The primary noninferiority efficacy endpoint is change in BCVA compared to the aflibercept control, approximately 6 months after the EYP-1901 injection. Secondary endpoints include safety, change in CST as measured by OCT, the number of eyes that remain free of supplemental anti-VEGF injections, and number of aflibercept injections in each group. More information about the trial is available at clinicaltrials.gov (identifier: NCT05381948).

EyePoint plans to present the DAVIO 2 dataset at Angiogenesis, Exudation, and Degeneration 2024 in February.

The company remains on track to reach additional clinical milestones with EYP-1901 with the initiation of the phase 2 VERONA trial in diabetic macular edema (DME) anticipated in the first quarter of 2024 and the readout of topline data from the phase 2 PAVIA trial in non-proliferative diabetic retinopathy (NPDR) anticipated in the second quarter of 2024.