EyePoint Pharmaceuticals announced positive results from its Phase II DAVIO 2 trial of EYP-1901 (vorolanib) for the treatment of wet age-related macular degeneration (wAMD) at the American Academy of Ophthalmology (AAO) 2024 meeting in Chicago. The study demonstrated that EYP-1901, an intravitreal tyrosine kinase inhibitor (TKI), was non-inferior to aflibercept in improving visual acuity, while significantly reducing the treatment burden for patients.
The DAVIO 2 trial (NCT05381948) enrolled 161 patients with wAMD who had previously responded to anti-VEGF therapy. Participants were randomized to receive either EYP-1901 2mg (n=53), EYP-1901 3mg (n=54), or aflibercept 2mg every eight weeks (q8W; n=54). Patients in the EYP-1901 arms received a single injection at week 8.
Efficacy and Safety Results
The primary endpoint of the study was met, with EYP-1901 demonstrating comparable efficacy to aflibercept q8W in terms of best corrected visual acuity (BCVA) change from baseline. At months 7 and 8, the blended average BCVA change from baseline was +1.0 letters for the EYP-1901 2mg group, +0.9 letters for the EYP-1901 3mg group, and +1.3 letters for the aflibercept q8W group. Optical coherence tomography (OCT) results showed that at month 8, the central subfield thickness (CST) change from baseline was +17.8 μm for EYP-1901 2mg, +10.6 μm for EYP-1901 3mg, and +5.4 μm for aflibercept q8W. By month 12, CST changes were +21.2 μm, +11.1 μm, and +11.2 μm, respectively.
Reduced Treatment Burden
EYP-1901 demonstrated a significant reduction in treatment burden. Patients receiving aflibercept q8W averaged 6.1 injections over 12 months, compared to an average of 1.8 injections for the EYP-1901 2mg group and 1.9 injections for the EYP-1901 3mg group, representing a 70% and 69% reduction, respectively. Furthermore, 43% of patients in the EYP-1901 2mg group and 46% in the EYP-1901 3mg group were injection-free up to month 14, reflecting an 81% and 80% reduction compared to pre-trial treatment.
The safety profile of EYP-1901 was favorable, with no ocular or systemic severe adverse events (SAEs) reported. While adverse events (AEs) were reported in 97% of participants, they were predominantly mild to moderate and anticipated due to the intravitreal route of administration. There were no treatment-related discontinuations, retinal occlusive vasculitis, or insert migrations into the anterior chamber.
Mechanism of Action and Future Directions
EYP-1901 contains vorolanib, a potent receptor tyrosine kinase inhibitor (TKI) that selectively inhibits VEGF receptors 1, 2, and 3. It is delivered via the Bioerodible Durasert E intravitreal insert, providing sustained drug release for over six months. The positive results from the DAVIO 2 trial support the initiation of Phase III trials, LUGANO and LUCIA, scheduled to begin later this year. These trials will further evaluate the efficacy and safety of EYP-1901 and its potential to compete with existing anti-VEGF therapies in the wAMD market.
