ODYSSEY: CLS-AX Maintains Stable Visual Acuity in Wet AMD Treatment

David M. Brown, MD

Credit: Retina Consultants of Texas

Axitinib injectable suspension (CLS-AX) achieved all primary and secondary outcomes in the treatment of neovascular (wet) age-related macular degeneration (AMD), according to topline data from the Phase 2b ODYSSEY trial.¹

Announced by Clearside Biomedical, on October 9, 2024, suprachoroidal CLS-AX demonstrated stability in visual acuity and anatomical control for up to 6 months, with a well-tolerated safety profile without ocular or treatment-related serious adverse events (SAEs).

“These data are encouraging and demonstrate that suprachoroidal CLS-AX may have sustained durability beyond our currently approved agents,” said David M. Brown, MD, director of research, Retina Consultants of Houston.¹ “The positive safety profile, potential flexible dosing, and delivery of CLS-AX directly to the back of the eye via Clearside’s SCS Microinjector has the potential to improve the treatment landscape for patients and physicians looking for a long-acting treatment for wet AMD.

CLS-AX is in development as a longer-acting therapy for retinal diseases, comprised of a proprietary suspension of axitinib for suprachoroidal injection.² Axitinib is a tyrosine kinase inhibitor (TKI) that achieves pan-vascular endothelial growth factor (VEGF) blockade by inhibiting VEGF receptors -1, -2, and -3, with high potency and specificity.

Clearside’s SCS Microinjector® delivers various drug candidates into the suprachoroidal space for targeted delivery to improve efficacy and compartmentalization of medication to reduce or eliminate toxic effects on non-diseased cells.³

Suprachoroidal injection of CLS-AX has demonstrated meaningful results in both Phase 1/2a and Phase 2b clinical trials in wet AMD, remaining well-tolerated and achieving a positive safety profile, according to Clearside.¹

The randomized, double-masked, parallel-group, active-controlled, multi-center, 36-week, Phase 2b ODYSSEY trial enrolled participants with wet AMD previously treated with anti-VEGF therapy. A total of 60 individuals were treated for 36 weeks and randomized to CLS-AX administered suprachoroidally via Clearside’s SCS Microinjector or intravitreal aflibercept 2 mg with a 2:1 randomization schedule.

Upon analysis, ODYSSEY achieved its primary outcome of maintaining stable vision with CLS-AX, as demonstrated by the mean change from baseline to Week 36 in best-corrected visual acuity (BCVA). CLS-AX maintained stable central subfield retinal thickness (CSRT) from baseline to Week 36, as confirmed by an independent reading center.

Results from ODYSSEY also revealed a consistent reduction in injection frequency after the initial CLS-AX dose. Approximately 90% of individuals treated with CLS-AX did not require additional treatment for up to 4 months, 81% did not require additional treatment for up to 5 months, and 67% did not require additional treatment for up to 6 months, before mandatory re-dosing at Week 24.

Overall, CLS-AX lowered injection frequency by nearly 84%, compared with average monthly injections received in the 24 weeks before the screening period. The drug demonstrated a well-tolerated safety profile through 36 weeks, without SAEs and showing no reports of endophthalmitis or retinal vasculitis.

Based on these topline data, Clearside suggested CLS-AX delivered into the suprachoroidal space can be flexibly dosed similar to current biologic treatments, with the potential for a longer-lasting impact given its high potency that achieves pan-VEGF blockade.¹

“Our goal is to provide a new and important treatment option with meaningful efficacy, safety, and delivery benefits for patients and retina specialists,” said Victor Chong, MD, MBA, chief medical officer of Clearside.¹ “These topline results provide valuable data in wet AMD with repeat dosing data to better inform our planned Phase 3 program design.”

References

1. _{Clearside biomedical announces positive topline results from Odyssey Phase 2B trial of suprachoroidal CLS-AX in wet AMD achieving all primary and secondary outcomes. Clearside Biomedical, Inc.- IR Site. October 9, 2024. Accessed October 9, 2024. https://ir.clearsidebio.com/news-releases/news-release-details/clearside-biomedical-announces-positive-topline-results-odyssey.}
2. _{CLS-ax (axitinib injectable suspension). Clearside Biomedical. September 19, 2024. Accessed October 9, 2024. https://clearsidebio.com/pipeline/cls-ax/.}
3. _{SCS Microinjector®. Clearside Biomedical. January 3, 2024. Accessed October 9, 2024. https://clearsidebio.com/technology/scs-microinjector/.}