Opthea Limited (ASX/NASDAQ: OPT), based in Melbourne, Australia and Princeton, New Jersey, have announced summary results from its global Phase 3 clinical trial “COAST” (Combination OPT-302 with Aflibercept Study) in patients with wet age-related macular degeneration (wet AMD). The global COAST Phase 3 trial evaluated the efficacy and safety of intravitreally administered 2 mg sozinibercept every four or eight weeks in combination with 2 mg aflibercept (Eylea), as per label, every eight weeks after a loading phase for the treatment of wet AMD. Following analysis of the results, the trial did not meet its primary endpoint of a mean change in best corrected visual acuity (BCVA) from baseline to week 52.
Sozinibercept (OPT-302) is a soluble form of vascular endothelial growth factor receptor 3 (VEGFR-3) expressed as an immunoglobulin G1 (IgG1) Fc-fusion protein. It binds and neutralizes the activity of VEGF-C and VEGF-D on their endogenous receptors, VEGFR-2 and VEGFR-3. Research indicates that targeted inhibition of VEGF-C and VEGF-D can prevent blood vessel growth and vascular leakage, which contribute to the pathophysiology of retinal diseases including wet AMD. Previously, sozinibercept received Fast Track Designation from the U.S. FDA for the treatment of wet AMD. Results from a Phase 2b study of sozinibercept, administered in combination with standard of care (ranibizumab) for the treatment of wet AMD, “met the pre-specified primary efficacy endpoint of a statistically superior gain in visual acuity at 24 weeks, compared to ranibizumab alone. In addition, secondary outcomes were positive for the combination therapy with sozinibercept, including more participants with gains in vision of 10 or more letters and improved anatomy, with a reduction in swelling and vascular leakage, with a favourable safety profile.”
In Phase 2b results, published at the company’s website (https://opthea.com/our-innovation/clinical-trials-in-wet-amd/sozinibercept-phase-2b-results/) results showed that sozinibercept combination therapy met the primary efficacy endpoint of a statistically significant superior gain in visual acuity of +3.4 letters at 24 weeks, compared to ranibizumab alone. The study used a large prospective, randomized and controlled Phase 2b clinical trial of 366 treatment-naïve wet AMD patients, showing that sozinibercept demonstrated superior vision outcomes in combination with standard-of-care ranibizumab compared to ranibizumab alone.
However, the more recent Phase 3 study used a dosing regimen of every four weeks (n=296) or every eight weeks (n=297) and the results achieved a mean change in BCVA of 13.2 or 13.2 letters, from baseline to week 52, respectively, versus 13.8 letters with aflibercept monotherapy (n=299, p-values of 0.59 and 0.62 respectively). The company stated that in the overall population, participants receiving sozinibercept combination therapy with a dosing regimen of every four weeks (n=333) or every eight weeks (n=330) achieved a mean change in BCVA of 13.5 and 12.8 letters from baseline to week 52, respectively, versus 13.7 letters with aflibercept monotherapy (n=330, p-values of 0.86 and 0.42 respectively). In addition, there was no difference observed in the key secondary endpoints.
Prior to the announcement, the manufacturing and commercial launch of sozinibercept was poised to expand activities in FY2025. However, following the outcomes of the COAST trial, Opthea’s board now has to consider next steps. In a press release from Opthea on March 24th, the company “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. The extension to the voluntary suspension is necessary to prevent trading in Opthea’s securities on an uninformed basis, pending further clarity on these issues being available and released to the market. Opthea is not aware of any reason why the voluntary suspension should not be extended or of any other information necessary to inform the market regarding the voluntary suspension.”