Opthea highlights latest phase 3 trials for sozinibercept

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Opthea recently held a conference call to provide key opinion leader (KOL) perspectives on the wet AMD treatment landscape, unmet medical needs addressed by the novel mechanism of action of sozinibercept (OPT-302), the phase 2b data demonstrating superiority of sozinibercept in combination with standard-of-care therapy, and the company’s 2 ongoing global phase 3 registrational trials—COAST (NCT04757636) and ShORe (NCT04757610)—evaluating sozinibercept in combination with standard-of-care VEGF-A inhibitors.¹

Presenting KOLs included Arshad M. Khanani, MD, MA, FASRS, of Sierra Eye Associates in Reno, Nevada, and University of Nevada, Reno School of Medicine; Charles C. Wykoff, MD, PhD, of Retina Consultants of Texas and Blanton Eye Institute, Houston Methodist Hospital in Texas; and Veeral S. Sheth, MD, MBA, FASRS, FACS, of University Retina and Macula Associates and the University of Illinois at Chicago.

Sozinibercept is a novel trap fusion protein that inhibits VEGF-C and VEGF-D, ligand mediators of angiogenesis and vascular leakage involved in retinal vascular diseases.

According to the company, the molecule is being evaluated in 2 phase 3 clinical trials for wet age-related macular degeneration (AMD) and is administered via intravitreal injection in combination with standard-of-care anti–VEGF-A therapy. These trials include the ShORe trial of 2 mg sozinibercept plus 0.5 mg ranibizumab (Lucentis) and the COAST trial of 2 mg sozinibercept plus 2 mg aflibercept (Eylea).

Khanani pointed out that the current unmet needs in treatment of wet AMD are improved efficacy, durability, and disease progression.

“We have made significant progress in addressing durability, with newer agents lasting longer. We are still working on [the] disease progression aspect in terms of reducing atrophy and fibrosis,” he said. “Today’s focus, obviously, is efficacy. When you look at the recent paper republished from 2-year data from the TENAYA (NCT03823287) and LUCERNE (NCT03823300) studies, what we see is that visual acuity gains start to decline in the second year of treatment.”

Khanani pointed out that when the data are examined more closely, 20% of participants gain 15 letters or more or less 3 lines, and 57% with 20/40 or greater, with driving vision, and 9% of patients had visual acuity of 20/200 or less.

“So clearly it has been a great advancement to have faricimab approved, but there is an unmet need to get better efficacy for our patients so they can be more independent,” he explained.

Khanani also cited results from the Preferences and Trends Survey conducted by the American Society of Retina Specialists, which in the past year found that more than 50% of respondents stated that durability and improved visual acuity for patients are the greatest unmet needs in treating wet AMD and diabetic macular edema.

Khanani noted that patients surveyed indicate they are seeking treatment because they want to see better.

“Vision outcomes are the No. 1 factor in patients’ anti-VEGF treatment preference,” he noted.

Wykoff then highlighted the development program of sozinibercept, with 3 clinical trials completed that were the foundation for the COAST and ShORe phase 3 trials.

“It is very important to understand where this molecule has come from,” he explained. “There are 3 trials that have been completed.”

Moreover, Wykoff pointed out that sozinibercept has the potential to transform wet AMD clinical practice. He detailed safety and efficacy demonstrated in findings from recent trials, concluding that sozinibercept stands alone as “the only drug in development that has demonstrated superiority in combination with anti–VEGF-A therapy.”

“In a large phase 2b trial involving 366 patients, we saw superior visual acuity gains for the combination compared with the gold standard of anti-VEGF therapy, which was monthly ranibizumab,” he added.

Wykoff added that trial designs that undertreat with a control arm for wet AMD are in stark contrast to the Opthea trial, which was monthly consistent anti–VEGF-A dosing in the control arm.

“In that context, we saw clinically meaningful improvement in visual acuity,” he said. “Importantly, we saw consistent anatomic improvements very supportive of the primary end point and the safety profile notably similar to monthly ranibizumab injections, with over 1800 injections of OPT-302 just through the phase 1 and phase 2 programs.”

Sheth then discussed the ongoing phase 3 clinical trials, which are studying sozinibercept in combination with both aflibercept and ranibizumab depending on the study, in treatment-naive patients with wet AMD.

“These phase 3 studies are designed to support broad label for use in combination with any VEGF-A inhibitor for all patients [with] wet AMD, treatment naive or previously treated,” he said.

The trial design is robust, with approximately 990 patients per trial, which breaks down to 330 patients per arm if they are randomly assigned 1:1:1.

“We are also breaking it down into looking at sozinibercept at 4-week intervals as well as 8-week intervals compared with the sham control,” Sheth said. “The comparators we’re using, depending on the study, [are the following]: in the COAST trial, we’re looking at 2 mg of Eylea [every] 8 weeks, and in the ShORe study, 0.5 mg Lucentis [every] 4 weeks.”

Sheth added the primary end point is mean change from baseline in best corrected visual acuity at week 52.

“These patients will be followed out to week 100, with the primary end point being at week 52,” he explained. “Key secondary end points include how many patients gained 15 letters or more—in other words, 3 lines of vision or more, 10 vision letters or more, as well as anatomic end points looking at choroidal neovascularization area in proportion of patients with absence of both subretinal fluid as well as intraretinal fluid or cysts.”

Sheth added that investigators are hoping to get top-line data from the COAST and ShORe trials by mid-2025. Enrollment in the ShORe trial should be completed by the end of the second quarter.

Reference:

1. Opthea Key Opinion Leader Event on Sozinibercept (OPT-302) in Wet Age-Related Macular Degeneration. LifeSci Events. April 4, 2024. Accessed April 9, 2024. Videocast available at: https://lifescievents.com/event/opthea/