Phase 3 Randomized Double-Masked Study of Vorolanib (EYP-1901) Versus Aflibercept in Patients with Wet Age-Related Macular Degeneration

The primary objective of this study is to evaluate the **efficacy** of EYP-1901, a tyrosine kinase inhibitor, in improving best corrected visual acuity (BCVA) in patients with wet age-related macular degeneration (wAMD) compared to aflibercept treatment. This is clinically relevant as BCVA is a critical measure of visual function and a key indicator of treatment success in wAMD, a condition that can lead to significant vision loss.

Secondary objectives include:

• Evaluating the efficacy of EYP-1901 IVT insert on injection burden through Week 56 and Week 96.
• Assessing the impact on retinal thickness fluctuation.
• Determining the effect on BCVA.
• Evaluating the need for supplemental injection treatment following administration of EYP-1901 IVT insert.
• Assessing the efficacy on retinal function and structure.

The clinical trial involves a total of **257 participants** diagnosed with **wet age-related macular degeneration (wAMD)**. The study population includes both male and female subjects aged 50 years and older. Participants were selected based on their ability to understand and sign informed consent, as well as their willingness to comply with scheduled visits and assessments. The trial includes individuals from a vulnerable population, and both genders are represented. Participants are required to use appropriate contraception if applicable. The study does not specify any particular lifestyle considerations such as diet or physical activity. The sponsor has not provided additional information regarding the general health status or specific lifestyle habits of the participants.

The clinical trial is a **Phase 3**, multicenter, prospective, randomized, double-masked, parallel-group study designed to evaluate the efficacy of EYP-1901, a tyrosine kinase inhibitor, compared to aflibercept in subjects with **wet age-related macular degeneration (wAMD)**. The trial aims to assess the changes in best corrected visual acuity (BCVA) over a period of 56 weeks, with a total study duration of up to 96 weeks. The study involves two main products: EYP-1901, administered as an intravitreal implant, and Eylea, a solution for injection in a pre-filled syringe, both delivered via intravitreal use.

Participants will be randomly assigned to receive either EYP-1901 or aflibercept, with the primary endpoint being the comparison of vision benefits between the two treatments over 56 weeks. Secondary endpoints include the total number of supplemental aflibercept injections required, changes in retinal thickness from Week 12 through Week 56, the number of injections needed up to 96 weeks, and changes in retinal structure and function over the 96-week period.

The trial will commence with a screening visit to determine eligibility based on inclusion criteria, such as age (≥50 years), ability to provide informed consent, and willingness to comply with study requirements. Women of childbearing potential and men with partners of childbearing potential must agree to use contraception. Following the screening, participants will undergo regular follow-up visits to monitor treatment effects and safety, with the final visit marking the end of the study.

Participant involvement is expected to last up to 96 weeks, with conditions for early termination including non-compliance with study protocols or adverse events that may compromise participant safety. The trial is scheduled to start recruitment in August 2025, with an estimated end date in February 2028.

The clinical trial involves the evaluation of **EYP-1901**, an experimental medication developed by EyePoint Pharmaceuticals Inc. EYP-1901 is an **implant** containing the active substance **vorolanib**, a tyrosine kinase inhibitor. The implant is designed for **intravitreal use** and is administered using a single-use syringe-type injector. The injector is equipped with a 22-gauge siliconized stainless-steel needle and is pre-loaded with two EYP-1901 inserts, which are sterilized prior to use. The maximum daily dose of EYP-1901 is 2686 micrograms, with a total maximum dose of 10744 micrograms over a treatment period of 96 weeks. The administration of EYP-1901 is intended to assess its efficacy in improving best corrected visual acuity (BCVA) in subjects with wet age-related macular degeneration (AMD).

The comparator treatment in this study is **Eylea**, a solution for injection containing the active substance **aflibercept**, manufactured by Bayer AG. Eylea is provided as a 40 mg/mL solution in a pre-filled syringe for **intravitreal use**. The maximum daily dose of Eylea is 2 milligrams, with a total maximum dose of 26 milligrams over the same 96-week treatment period. Aflibercept acts as a vascular endothelial growth factor (VEGF) trap, and its efficacy in treating wet AMD is well-documented. The study aims to compare the changes in BCVA between subjects receiving EYP-1901 and those receiving aflibercept, with both treatments administered according to their respective dosing schedules.

The efficacy of the clinical trial will be assessed by evaluating the changes in **best corrected visual acuity (BCVA)** in subjects with wet age-related macular degeneration (AMD). The primary endpoint is to determine whether EYP-1901 can produce the same vision benefits as aflibercept over a period of 56 weeks. Secondary endpoints include the total number of supplemental injections of aflibercept required over the 56 weeks, changes in the thickness of the retina from Week 12 through Week 56, the number of injections needed up to 96 weeks, and changes in the retina's structure and function over the 96 weeks of treatment.

Measurements will be collected at specified timepoints, including Week 12 and Week 56, with additional assessments extending up to 96 weeks. The trial employs a randomized, double-masked, parallel-group design to ensure objective evaluation of the efficacy parameters. The use of validated scales and instruments for measuring BCVA and retinal thickness will be integral to the assessment process. The trial aims to provide comprehensive data on the efficacy of EYP-1901 compared to aflibercept, contributing to the understanding of treatment options for wet AMD.