Opthea's Wet AMD Program Halted After Dual Phase 3 Failures

Sozinibercept Falls Short in Clinical Trials

Australian biotech company Opthea has announced the termination of its wet age-related macular degeneration (AMD) program following two consecutive phase 3 trial failures. The company's lead drug candidate, sozinibercept, an inhibitor of vascular endothelial growth factors (VEGFs) C and D, failed to meet its primary endpoints in both the Coast and Shore studies.

In the Coast trial, sozinibercept was unable to outperform Regeneron's established VEGF inhibitor, Eylea. The subsequent Shore trial, which evaluated sozinibercept in combination with Novartis' Lucentis, also failed to demonstrate superiority over Lucentis monotherapy.

Clinical Data and Trial Results

The Shore trial, involving 985 patients, compared two dosing regimens of sozinibercept (2 mg every four or eight weeks) combined with 0.5 mg Lucentis every four weeks against Lucentis alone. The primary outcome measure was the improvement in best corrected visual acuity (BCVA) from baseline at Week 52.

Results showed that patients receiving the combination therapy achieved mean BCVA changes of 13.3 letters (four-week regimen) and 12.6 letters (eight-week regimen). In contrast, the Lucentis monotherapy group demonstrated a superior mean BCVA change of 14.3 letters.

Financial Implications and Company Outlook

The dual trial failures have placed Opthea in a precarious financial position. With approximately $100 million in cash and equivalents on hand, the company is engaged in "active discussions" with investors to avoid potential defaults on its debts and additional charges.

Opthea has warned of "material uncertainty" regarding its ability to continue as a going concern. The company's pipeline now appears limited, with sozinibercept previously described as "phase 3 ready" for diabetic macular edema, another eye disease. However, no other ongoing trials are currently reported.