Despite anti-VEGF advancements, durable therapies are needed to improve long-term outcomes.
Wet AMD and DME are complex diseases that require more than VEGF suppression.
TKIs work intracellularly to inhibit the key receptors and pathways involved in wet AMD and DME pathogenesis.
EYP-1901 (vorolanib intravitreal insert), a sustained-release TKI, uniquely inhibits all VEGF receptors, PDGFR, and pro-inflammatory IL-6 signaling.
It is designed to deliver a continuous daily dose for at least 6 months.
EYP-1901 was well tolerated and met primary and key secondary endpoints in wet AMD/DME phase 2 trials.
It is currently in phase 3 for wet AMD and DME.
EYP-1901 combines vorolanib with the Durasert E technology to deliver a continuous daily dose for at least 6 months. It is currently being investigated in pivotal phase 3 trials for the treatment of wet AMD and DME.
To date, EYP-1901 has been studied in >190 patients across four phase 1 and 2 clinical trials, with a favorable safety profile. A recent independent review of the phase 3 LUGANO/LUCIA masked safety data showed that the observed safety profile is consistent with previous EYP-1901 clinical trials.
Blocks signaling from all VEGF isoforms and PDGF at the receptor level and uniquely inhibits IL-6 pro-inflammatory signaling
Therapeutic levels of vorolanib reached within hours*
Consistent daily dosing for ≥6 months
No free-floating drug particles
Preloaded sterile IVT syringe injector; to be shipped and stored at an ambient temperature
*Data from preclinical studies. Following a single EYP-1901 900-µg dose in Dutch-Belted rabbits, vorolanib reached concentrations exceeding IC50 in the choroid and retina within hours of administration.
Vorolanib intracellularly binding to VEGFR
*Data from preclinical studies. Following a single EYP-1901 900-µg dose in Dutch-Belted rabbits, vorolanib reached concentrations exceeding IC50 in the choroid and retina within hours of administration.
Vorolanib, a small molecule TKI, works intracellularly, binding to key receptors involved in wet AMD and DME pathogenesis, while anti-VEGFs act extracellularly binding to select VEGF ligands.
Vorolanib is a TKI that uniquely binds to VEGFR-1/2/3, PDGFR, and JAK-1, to inhibit angiogenic and IL-6 pro-inflammatory signaling.
PDGF contributes to pathological fibrosis and pericyte recruitment, potentially leading to treatment resistance.
Vorolanib acts within endothelial cells to inhibit the downstream activation of VEGFR-1/2/3, PDGFR, and IL-6 pro-inflammatory signaling.
Vorolanib has been shown to:
Site of Action
Intracellular
MOA
A small molecule that binds to receptor tyrosine kinases
Target Profile
Delivery and Durability
Sustained release: a continuous daily dose for at least 6 months
Site of Action
Extracellular
MOA
Biologics bind to VEGF ligands, thereby preventing the receptor from being activated
Target Profile
Primarily targeting VEGF-A†
Delivery and Durability
Rapid vitreous clearance limits durability and requires frequent injections, 4-16 weeks
†Anti-VEGFs with additional targets: aflibercept binds placental growth factor (PlGF); faricimab-svoa binds angiopoietin-2 (Ang2).
Durasert E™ is an investigational next-generation bioerodible intravitreal insert that delivers a continuous daily dose of vorolanib over the course of 6 months.
Durasert® technology, the predecessor to Durasert E, has been proven safe following use in thousands of eyes across 4 FDA-approved products: Vitrasert®, Retisert®, ILUVIEN®, and YUTIQ®.
For illustrative purposes only. Insert not to scale.
Each insert is:
For illustrative purposes only.
EYP-1901 combines vorolanib with next-generation Durasert E technology to deliver a continuous daily dose for at least 6 months.
AMD, age-related macular degeneration; DME, diabetic macular edema; FDA, US Food & Drug Administration; IC, inhibitory concentration; IVT, intravitreal; MOA, mechanism of action; PDGFR, platelet-derived growth factor receptor; PEG, polyethylene glycol; PLGA, poly lactic-co-glycolic acid; TKI, tyrosine kinase inhibitor; VEGF, vascular endothelial growth factor.
EYP-1901 is an investigational medicinal product and is not authorized for sale in any country at the time of this publication. FDA approval in the US, Marketing Authorization in any other country, and the timeline for potential approval or authorization is uncertain. DURAVYU has been conditionally accepted by the US FDA as the proprietary name for EYP-1901 (vorolanib intravitreal insert).
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