Opthea Publishes on VEGF-C/D Pathways as Wet AMD Targets

Opthea Limited, a biopharmaceutical company focused on developing innovative treatments for prevalent and progressive retinal diseases, has announced the publication of a scientific review in the journal Ophthalmology and Therapy. The review, titled "Vascular Endothelial Growth Factor (VEGF) C and D Signaling Pathways as Potential Targets for the Treatment of Neovascular (wet) AMD," provides a strong scientific basis for considering sozinibercept (OPT-302) as a potential treatment for wet age-related macular degeneration (wet AMD).

Wet AMD is a leading cause of vision loss in the elderly, affecting approximately 3.5 million individuals in the United States and Europe. Despite the availability of anti-VEGF-A therapies, many patients do not achieve optimal visual outcomes. This highlights the significant unmet medical need for more effective treatments.

The review discusses how the pathophysiology of retinal diseases, such as wet AMD, involves more than just the dysregulation or overproduction of VEGF-A. While current therapies primarily target VEGF-A signaling, research indicates that VEGF-C and VEGF-D signaling pathways also play crucial roles in the development of these diseases. The publication emphasizes the need for new therapeutic strategies that address these additional mechanisms to achieve better visual outcomes for patients.

Opthea's CEO, Frederic Guerard, highlighted the potential of sozinibercept as a novel, first-in-class VEGF-C/D 'trap' designed to prevent blood vessel growth and vascular leakage in the retina. When combined with standard-of-care anti-VEGF-A therapies, sozinibercept aims to deliver superior visual outcomes for patients with wet AMD. Opthea's Phase 3 clinical program for sozinibercept includes two fully enrolled, concurrent, multicenter, double-masked, randomized clinical trials: COAST (Combination OPT-302 with Aflibercept Study) and ShORe (Study of OPT-302 in combination with Ranibizumab). These trials are designed to evaluate the safety and superior efficacy of sozinibercept in combination with standard-of-care therapies.

The Phase 3 program aims to support a broad label for sozinibercept, potentially allowing its use in combination with any anti-VEGF-A therapy for wet AMD patients. The company expects to report topline data for the COAST trial in early Q2 and for the ShORe trial in mid-2025. Sozinibercept has also received Fast Track Designation from the US FDA for the treatment of wet AMD.

In a previous Phase 2b trial involving 366 treatment-naïve wet AMD patients, sozinibercept was administered alongside standard-of-care ranibizumab. The combination therapy achieved the primary efficacy endpoint of a statistically significant improvement in visual acuity at 24 weeks compared to ranibizumab alone. Secondary outcomes were also positive, including a higher number of patients gaining vision of 10 or more letters, improved anatomical outcomes, reduced swelling, and vascular leakage, as well as a favorable safety profile. These significant results were published in the journal Ophthalmology in February 2023.

Opthea is dedicated to addressing the unmet needs in the treatment of retinal diseases, including wet AMD and diabetic macular edema (DME). The company's lead product candidate, sozinibercept, is currently being evaluated in pivotal Phase 3 clinical trials for use in combination with standard-of-care anti-VEGF-A monotherapies. The goal is to enhance overall efficacy and provide superior vision gains compared to existing treatments.

Opthea remains committed to advancing its clinical development program to bring effective and innovative therapies to patients suffering from retinal diseases, ultimately aiming to improve their quality of life through better visual outcomes.