Opthea Limited reported that top-line data from its phase 3 COAST trial indicates that sozinibercept (OPT-302), a treatment for wet age-related macular degeneration (AMD), did not meet its primary endpoint. The study, which evaluated sozinibercept in combination with aflibercept 2 mg (Eylea; Regeneron), showed no significant improvement in best-corrected visual acuity (BCVA) compared to aflibercept alone.

In wet AMD patients, participants receiving sozinibercept combination therapy with a dosing regimen of every 4 weeks (n=296) or every 8 weeks (n=297) achieved a mean change in BCVA of 13.2 or 13.2 Early Treatment Diabetic Retinopathy Scale (ETDRS) letters from baseline to week 52, respectively, vs 13.8 letters with aflibercept monotherapy (n=299, P-values of 0.59 and 0.62, respectively). In the overall population, participants receiving sozinibercept combination therapy with a dosing regimen of every 4 weeks (n=333) or every 8 weeks (n=330) achieved a mean change in BCVA of 13.5 and 12.8 letters from baseline to week 52, respectively, vs 13.7 letters with aflibercept monotherapy (n=330, P-values of 0.86 and 0.42, respectively). There was no numerical difference observed in the key secondary endpoints, and sozinibercept combination therapy was well tolerated.

Following these trial results, Opthea is assessing its financial position under its Development Funding Agreement (DFA). The company may be required to repay up to $680 million to its investors, which could affect its solvency. Discussions with DFA investors are ongoing. Opthea has suspended trading on ASX and Nasdaq while evaluating its options. The company holds $113.8 million in cash as of February 28, but material uncertainty remains regarding its ability to continue operations.

Sozinibercept is an Fc-fusion protein designed to inhibit VEGF-C and VEGF-D after intravitreal injection. It is also being evaluated in the phase 3 ShORe trial as a combination treatment with ranibizumab (Lucentis; Genentech); results are expected later in 2025.