Safety results for DAVIO trial: Positive outcomes for EYP-1901 for wet AMD

Reviewed by Dr Jay S. Duker.

An EYP-1901 implant in the vitreous cavity of a patient from the DAVIO trial. (Image courtesy of Dr Jay S. Duker)

Positive safety results from the Phase 1 DAVIO clinical trial were seen for the DuraSert implant (EYP-1901, Vorolanib, EyePoint Pharma), a bio-erodible implant for previously treated wet age-related macular degeneration (AMD), according to Dr Jay S. Duker, Chief Operating Officer, who reported the 8-month results at the Angiogenesis, Exudation, and Degeneration 2022 Conference.

“The major unmet need in current wet AMD therapy is longer term therapies, in that the currently approved therapies typically need to be reinjected very 1 to 2 months in most patients,” Dr Duker explained. EYP-1901, is an anti-vascular endothelial growth factor (VEGF) treatment that may meet that need. It is delivered as an in-office intravitreal injection with the potential for every six month dosing intervals in most patients.

The key safety findings with EYP-1901, a tyrosine kinase inhibitor (vorolanib) in a bio-erodible form of DuraSert, with a minimum of 8 months of follow-up of all eyes were that no ocular serious adverse events (SAEs) were reported in any eyes. The majority of ocular AEs were mild and to be expected from intravitreal injections.

“Specifically, there were no reported SAEs related to significant intraocular inflammation, best-corrected visual acuity [BCVA] reduction, intraocular pressure elevation, and no endophthalmitis, vitritis, retinal detachment, migration of the inserts into the anterior chamber, or retinal vasculitis,” he commented. In addition, there were no drug related systemic SAEs reported

The results also showed stable VA and central subfield thickness (CST) on optical coherence tomography (OCT) over 8 months. The median time to the first supplemental anti-VEGF treatment after EYP-1901 was 6 months. Specifically, the study showed that 76% of eyes did not require a supplemental anti-VEGF treatment up to 4 months, 53% of eyes did not require a supplemental anti-VEGF treatment up to 6 months, and 41% of eyes did not require a supplemental anti-VEGF treatment up to 9 months, Dr Duker reported.

These results lead to clinically significant reductions in treatment burden: a 79% reduction in treatment burden at 6 months and a 75% reduction at 8 months.

DAVIO trial design

This is a Phase 1, open-label, dose-escalation, clinical trial of EYP-1901 that enrolled 17 patients all of whom had previously treated wet AMD. One week after screening and a standard-of-care anti-VEGF injection, the patients received 1 injection of EYP-1901. No retreatments with EYP-1901 occurred in this trial.

The primary study endpoint was safety; the secondary endpoints were BCVA and CST measured by OCT.

The investigators also looked at both the number of eyes that did not require rescue treatment at various time points and the degree to which the anti-VEGF treatment burden was reduced after administration of EYP-1901.

The study included four dosing cohorts: low dose (440 ug, single dose), low medium dose (1,030 ug, single dose), mid dose (2,060 ug, single dose), and high-dose (3,090 ug, single dose).

The patients included in this study had diagnosed wet AMD in the study eye for at least 4 months prior to the screening visit. All patients had to have received at least 3 previous injections with an anti-VEGF product in the study eye, such as bevacizumab (Avastin, Genentech), ranibizumab, (Lucentis, Genentech), or aflibercept (Eylea, Regeneron) during the previous 6 months and a BCVA between 25 letters (20/320 Snellen equivalent) and 75 letters (20/32 Snellen equivalent).

The future for EYP-1901 includes advancing into three Phase 2 clinical trials by 2023, start of a wet AMD Phase 2 trial expected in the third quarter of 2022 (3 arms: 3 mg EYP-1901, 2 mg EYP-1901; Eylea control), start of a study to treat diabetic retinopathy expected in the second half of 2022, and a study to treat retinal vein occlusion beginning expected by Q1 2023.

“With EYP-1901, the sustained, stable release over 6 months or longer may lead to fewer patient visits, fewer injections, and possibly better visual outcomes through uninterrupted receptor blockade. In addition, EYP-1901 has the potential for up to every 6-month dosing, which would address adherence issues and, therefore, possibly treat wet AMD more effectively,” Dr Duker concluded.