Opthea, Unity Candidates Miss Clinical Trial Endpoints vs. Aflibercept

Opthea and Unity Biotechnology reported results March 24 for their retinal treatment candidates that failed to meet or beat Regeneron’s Eylea (aflibercept) in clinical trials for wet AMD and DME, respectively.

Opthea Results

Opthea, of South Yarra, Australia, is developing sozinibercept (OPT-302) a VEGF-C/D “trap” designed to be used in combination with standard-of-care anti-VEGF-A therapies in wet age-related macular degeneration (AMD), with the goal of delivering superior visual outcomes. 

The Phase III COAST trial evaluated intravitreally (IVT) administered 2 mg sozinibercept every four or eight weeks in combination with 2 mg aflibercept, as per label, every eight weeks after a loading phase in wet AMD patients. The trial did not meet its primary endpoint of mean change in best corrected visual acuity (BCVA) from baseline to week 52.

Patients receiving sozinibercept combination therapy every four weeks (n=333) or every eight weeks (n=330) achieved a mean change in BCVA of 13.5 and 12.8 letters, respectively, vs. 13.7 letters with aflibercept monotherapy (n=330).

Sozinibercept is Opthea’s only pipeline candidate. The company said it was weighing whether to discontinue activities for the COAST trial or unmask the Phase III ShORe study in wet AMD ahead of its expected readout in mid-2025.

The poor results could put the company in financial straits. Opthea asked Nasdaq and the Australian Securities Exchange to pause trading of its stock. The company said in a press release that it could have to pay certain investors up to $680 million if those investors terminate a financing contract. Opthea reported having $113.8 million in cash on hand at the end of February.

Unity Results

Unity, of South San Francisco, California, is developing UBX1325,  a small molecule inhibitor of Bcl-xL, a member of the Bcl-2 family of apoptosis-regulating proteins. UBX1325 is designed to inhibit the function of proteins that senescent cells rely on for survival.

The Phase IIb ASPIRE trial evaluated IVT-administered UBX1325 vs. aflibercept in diabetic macular edema (DME) patients who had poor vision despite prior anti-VEGF treatment. 

Treated patients saw visual acuity gains of over five letters from baseline at weeks 24 and 36, and achieved non-inferiority to aflibercept at nine out of 10 time points through 36 weeks, Unity said—except for the average of weeks 20 and 24, where it achieved non-inferiority at an 88 percent confidence interval, vs. the 90 percent threshold that served as the study’s primary endpoint.

UBX1325 also failed to achieve non-inferiority vs. aflibercept in Part A of its Phase II ENVISION study in wet AMD, and that indication was dropped from its development.

Despite the narrow miss in DME, Unity officials did see a path forward for the candidate, for patients who are difficult to treat.

“We look forward to advancing UBX1325 to late-stage studies against aflibercept in DME patients with inadequate response to anti-VEGF therapies,” Unity CEO Anirvan Ghosh said in a statement.