Design and function of EYP-1901, a sustained-release platform for retinal/choroidal diseases: pan–vascular endothelial growth factor receptor inhibitor vorolanib in a bioerodible intravitreal insert

Abstract

Purpose : Therapies are needed to lower treatment burden for vascular endothelial growth factor (VEGF)–driven ocular diseases such as wet age-related macular degeneration (wAMD). Such therapies need to address safety, efficacy, and durability of treatment. EYP-1901 is a bioerodible, intravitreal (IVT), extended-release insert designed to deliver vorolanib, a pan–VEGF receptor (VEGFR) inhibitor, over a period of ~9 months. The insert is a bioerodible version of the Durasert® platform that is safely used in multiple FDA-approved IVT insert products. EYP-1901 is a novel approach being studied to reduce treatment burden vs standard of care while maintaining vision in eyes with wAMD.

Methods : EYP-1901 was studied in phase 1 (DAVIO) and phase 2 (DAVIO 2) clinical trials in wAMD. The vorolanib mechanism of action was studied in vitro and in vivo. EYP-1901 pharmacokinetics were studied in rabbit eyes.

Results : EYP-1901 was well tolerated in DAVIO and DAVIO 2, with no EYP-1901–related serious ocular or systemic adverse events. In DAVIO 2 a single injection of EYP-1901 was noninferior to on-label aflibercept over 6 months with respect to BCVA. Positive anatomic findings and treatment burden reduction were seen. Nearly 2/3 of eyes treated with EYP-1901 were injection-free up to 6 months (Fig 1). Vorolanib inhibited all VEGFRs in vitro and blocked VEGF-induced angiogenesis more effectively than the anti-VEGF antibody bevacizumab in vivo. In preclinical PK studies, EYP-1901 showed drug release with zero-order kinetics, exposure of target ocular tissues to near steady state levels within 4 hours, and stable therapeutic levels through 8 months (Fig 2). Reinjection at month 4 showed stable kinetics over 12 months. Plasma was below its half-maximal inhibitory concentration for VEGFR2, supporting the systemic safety observed in clinical trials.

Conclusions : EYP-1901 is a maintenance therapy for VEGF-driven ocular diseases that may provide safe, rapid, and durable IVT delivery of a pan-VEGFR inhibitor with no evidence of compromise of vascular stability. EYP-1901 is also being studied in nonproliferative diabetic retinopathy and diabetic macular edema, and a phase 3 trial in wAMD is planned.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Fig 1 Injection-free rates in eyes with no excess fluid at screening in DAVIO

 

Fig 2 Vorolanib levels in eyes injected with EYP-1901