Phase 3 COAST trial fails to meet primary endpoints for wet AMD, Opthea reports

the trial did not meet its primary endpoint of mean change in best corrected visual acuity from baseline to week 52. Image credit: ©Matthew Benoit – stock.adobe.com

Opthea announced results from COAST, its phase 3 clinical trial, in patients with wet age-related macular degeneration (wet AMD). According to the company, the trial did not meet its primary endpoint of mean change in best corrected visual acuity (BCVA) from baseline to week 52.

COAST (Combination OPT-302 with Aflibercept Study) evaluated sozinibercept (2 mg) every 4 or 8 weeks in combination with aflibercept (2 mg), as per label, every 8 weeks after a loading phase for the treatment of wet AMD.

In wet AMD patients with minimally classic and occult lesions, 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 letters from baseline to week 52, respectively, compared to 3.8 letters with aflibercept monotherapy (n=299).

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, compared to 13.7 letters with aflibercept monotherapy (n=330).

In a press release, Opthea noted that, following the negative results, the company has been assessing its rights and obligations under its Development Funding Agreement (DFA) with investors and other stakeholders. Opthea stated that under the DFA, it is possible that a requirement to pay amounts to its DFA investors would have a materially adverse impact on the solvency of the company.

Furthermore, it was stated that certain instances and events may result upon the termination of the DFA. This would result in Opthea paying DFA investors up to 4 times the amounts paid to the company under the DFA. Termination of the DFA can be triggered by the inability of Opthea to fund development costs, failure by Opthea to continue to use commercially reasonable efforts to develop sozinibercept, Opthea’s insolvency or disagreement with the DFA investors, among other events.

The company noted that its board of directors has been in active discussions with the DFA investors to explore possible options for the company “in respect of its clinical trial programme and with a view to identifying whether there is a pathway that represents the best outcome for the company and its shareholders.”

Opthea also stated that at this stage, no decision has been taken with respect to either the COAST (NCT04757636) or ShORe (NCT04757610) trials, including whether to discontinue activities for the COAST trial or accelerate and unmask the ShORe trial.

The company stated in the press release that “there remains material uncertainty as to Opthea's ability to continue as a going concern.” Additionally, per the press release, Opthea "has requested that trading in its listed securities continue to be suspended on both ASX and Nasdaq until the earlier of Opthea being in a position to provide an announcement to the market by Opthea providing more clarity on these issues or the commencement of trading on Monday, 31 March 2025."

References:

1. Opthea announces COAST phase 3 trial topline results. Opthea. Published March 24, 2025. Accessed March 24, 2025. https://ir.opthea.com/news-releases/news-release-details/opthea-announces-coast-phase-3-trial-topline-results