Opthea Limited today announced it will discontinue development of sozinibercept for neovascular (“wet”) age-related macular degeneration (nAMD) after its phase 3 trials failed to meet primary endpoints. The decision follows negative results from the COAST and ShORe studies, which evaluated the drug in combination with 2 standard nAMD treatments.
Sozinibercept is an Fc-fusion protein designed to inhibit VEGF-C and VEGF-D after intravitreal injection. The ShORe trial, which compared sozinibercept plus ranibizumab 0.5 mg (Lucentis; Genentech) to ranibizumab alone, did not show a statistically significant improvement in best-corrected visual acuity (BCVA) over 52 weeks. Patients receiving the combination therapy had mean BCVA gains of 12.6 to 13.3 Early Treatment Diabetic Retinopathy Scale (ETDRS) letters, compared to 14.3 letters with ranibizumab monotherapy.
Last week Opthea reported top-line data from COAST, which evaluated sozinibercept in combination with aflibercept 2 mg (Eylea; Regeneron). The data show no significant improvement in BCVA compared to aflibercept alone, with nAMD patients achieving a mean change in BCVA of 13.2 or 13.2 ETDRS letters from baseline to week 52, respectively, vs 13.8 letters with aflibercept monotherapy.
“We are disappointed that COAST and ShORe did not demonstrate the improvements in vision with sozinibercept combination therapy compared to standard of care that we had hoped for,” said Frederic Guerard, PharmD, Opthea’s chief executive officer. “We are grateful to all patients, clinical investigators and their staff around the world who participated in the sozinibercept phase 3 clinical program, and for their contributions in investigating new treatments for wet AMD.”
Opthea and its Development Funding Agreement (DFA) investors have agreed to terminate both trials, the company said. While this decision does not immediately trigger financial penalties, Opthea’s obligations under the DFA could impact the company’s solvency. Opthea estimates it will have $100 million in cash reserves at the end of March but acknowledged uncertainty about its ability to continue operations. Trading of Opthea’s securities has been suspended, pending further announcements regarding its financial position and discussions with DFA investors. RP