Dual VEGF-A/ANG-2 Inhibitor Shows Promise in Wet AMD Phase 2a Trial

A novel dual-action therapy, VIS-101, is demonstrating promising results in the treatment of wet age-related macular degeneration (AMD), a leading cause of vision loss in older adults. Early findings from a phase 2a study suggest both safety and rapid improvements in visual acuity, offering a potential new option for patients who currently rely on frequent injections to manage the condition. The data, released by NovaBridge and Visara, indicate that VIS-101 targets multiple pathways involved in the disease process, potentially leading to more durable treatment effects.

Wet AMD occurs when abnormal blood vessels grow under the retina, leaking fluid and causing vision distortion. Current treatments primarily focus on inhibiting vascular endothelial growth factor A (VEGF-A), a key driver of these blood vessel changes. Yet, some patients don’t respond fully to anti-VEGF therapies and frequent injections are often required to maintain vision. VIS-101 distinguishes itself by simultaneously inhibiting both VEGF-A and angiopoietin-2 (ANG-2), another protein implicated in blood vessel instability, and inflammation. Age-related macular degeneration affects millions worldwide, and new treatment options are urgently needed.

Study Details and Initial Findings

The phase 2a study, conducted in China, involved 38 patients with wet AMD. Participants were randomly assigned to receive either 6 mg of VIS-101 or 3 mg of VIS-101. The primary goal of the study was to assess the safety and how the drug is processed by the body (pharmacokinetics). Researchers also evaluated changes in best-corrected visual acuity (BCVA), central subfield thickness (CST) – a measure of retinal swelling – and the need for additional treatment (retreatment rate).

The results showed that VIS-101 led to rapid and sustained improvements in both groups. The average improvement in BCVA exceeded 10 ETDRS letters (a standard measure of visual acuity), and a notable reduction in CST was observed, ranging from 100 to 150 µm. Importantly, approximately two-thirds of patients did not require retreatment at the 4-month mark, and around half remained retreatment-free for over 6 months. This suggests a potential for less frequent injections compared to existing therapies. The safety profile was also encouraging, with no dose-limiting toxicities reported.

Understanding VEGF-A and ANG-2 Inhibition

VEGF-A has long been a target in wet AMD treatment, but research suggests that targeting ANG-2 alongside VEGF-A could offer additional benefits. ANG-2 plays a role in destabilizing blood vessels and promoting inflammation, contributing to the progression of the disease. By inhibiting both pathways, VIS-101 aims to provide a more comprehensive approach to stabilizing blood vessels and reducing retinal swelling. Reducing the frequency of treatment is a major goal in AMD management, as frequent injections can be burdensome for patients and carry potential risks.

What the Data Doesn’t Tell Us

While the phase 2a results are promising, it’s crucial to acknowledge the study’s limitations. The sample size of 38 patients is relatively small, and the study was conducted in a single country (China). This raises questions about whether the findings will be generalizable to other populations. The study duration was limited to 6 months, so the long-term durability of the treatment effect remains unknown. The study primarily focused on safety and initial efficacy; larger, longer-term studies are needed to confirm these findings and assess the potential for sustained vision improvement.

Next Steps in VIS-101 Development

NovaBridge and Visara are planning a phase 2b dose-determining study in the latter half of 2026. This study will aim to identify the optimal dose of VIS-101 for maximizing efficacy and minimizing side effects. Following the phase 2b study, the companies intend to initiate a global phase 3 program in 2027. Phase 3 trials are typically larger and more rigorous, designed to confirm the efficacy and safety of a treatment before it can be approved for widespread use. The progression through these phases is standard for drug development, and each stage provides increasingly robust evidence.

Emmett T. Cunningham Jr., MD, PhD, MPH, founder and executive chairman of Visara, expressed optimism about the potential of VIS-101. “The data validates VIS-101’s purpose-engineered design and gives us added confidence in its potential to deliver best-in-class durability while maximizing visual gains in the treatment of wet AMD,” he stated in a press release. He also highlighted the potential for reduced treatment burden, with nearly half of patients remaining retreatment-free for over 6 months following initial treatment.

The development of VIS-101 represents a potential step forward in the treatment of wet AMD. While further research is needed, the initial findings suggest that this dual-action therapy could offer a more effective and convenient option for patients struggling with this sight-threatening condition. Individuals concerned about their risk of AMD or experiencing vision changes should consult with a qualified ophthalmologist for a comprehensive eye exam and personalized advice. You can find more information about AMD and available treatments from organizations like the American Academy of Ophthalmology.