Clearside Biomedical Presents New Data from ODYSSEY Phase 2b Trial on CLS-AX

Clearside Biomedical has shared new insights from two subgroup analyses of its ODYSSEY Phase 2b clinical trial, evaluating CLS-AX (axitinib injectable suspension) for neovascular age-related macular degeneration (wet AMD). These findings were presented at the Angiogenesis, Exudation, and Degeneration 2025 meeting and are expected to influence the design of the upcoming CLS-AX Phase 3 clinical trials.

ODYSSEY Phase 2b: Study Overview

The ODYSSEY trial is a 36-week, randomized, double-masked, parallel-group, active-controlled, multicenter study assessing the efficacy and safety of CLS-AX in wet AMD patients.

The data presentation, led by Roger Goldberg, MD, of Bay Area Retinal Associates Medical Group, highlighted the latest findings and the differentiated mechanism of CLS-AX—a highly potent, selective pan-VEGF tyrosine kinase inhibitor (TKI) administered via suprachoroidal injection using Clearside Biomedical’s SCS Microinjector.

Key Findings: CLS-AX Demonstrates Durability While Maintaining Vision

According to Victor Chong, MD, Chief Medical Officer and EVP, Head of Research and Development at Clearside Biomedical, these subgroup analyses reinforce the potential of CLS-AX as a durable treatment for wet AMD while preserving visual acuity.

"The subgroup data from our ODYSSEY Phase 2b trial provided us with key clinical insights that contributed to the design of our planned CLS-AX Phase 3 non-inferiority clinical trials," Dr. Chong stated.

He further noted that these results support plans to enroll a broad population of treatment-naïve patients while refining eligibility criteria to minimize non-disease-related variability in visual acuity at randomization, ensuring real-world applicability of the Phase 3 trial data.

Subgroup Analysis 1: Supporting the Enrollment of Treatment-Naïve Patients

The first subgroup analysis highlights the stabilization of best corrected visual acuity (BCVA) and central subfield thickness (CST) in patients who were re-dosed with CLS-AX at week 24 and did not require aflibercept rescue or CLS-AX re-dosing before week 24.

Notably, 67% of participants in the CLS-AX arm did not need aflibercept rescue or additional CLS-AX re-dosing for six months, demonstrating the long-lasting effects of CLS-AX in maintaining retinal health.

Subgroup Analysis 2: Refining Eligibility to Reduce Variability in BCVA

The second subgroup analysis supports excluding participants from the Phase 3 trial who exhibit significant non-disease-related fluctuations in visual acuity before randomization.

By removing data from patients who showed a greater than 10-letter change in BCVA without a corresponding 50-micron CST change, the analysis provided strong evidence that excluding this group could help reduce BCVA variability unrelated to wet AMD activity.

Implications for CLS-AX Phase 3 Development

These findings are expected to shape the design of the upcoming CLS-AX Phase 3 non-inferiority trials, ensuring that data reflects real-world treatment scenarios while enhancing trial consistency.

With its differentiated pan-VEGF TKI mechanism and suprachoroidal administration, CLS-AX continues to show promise as a long-lasting treatment option for wet AMD, potentially reducing the burden of frequent injections for patients.