Medical Device Network

Clearside’s wet AMD drug-device combo shines in Phase IIb study

Clearside is now looking at a Phase III trial as it plans to meet with the FDA early next year to discuss the new Phase IIb topline results.

Clearside Biomedical’s Phase IIb ODYSSEY study of its drug-device combination CLS-AX (axitinib injectable suspension) has successfully achieved its primary and secondary endpoints in patients with neovascular age-related macular degeneration (wet AMD).

Clearside’s investigative treatment is injected into the suprachoroidal space in the eye – the area between the sclera and choroid – enabling minimally invasive, targeted delivery via its SCS Microinjector. This method may offer advantages compared to standard of care therapies, which are typically administered directly into the vitreous cavity of the eye.

In the ODYSSEY study (NCT05891548), patients treated with CLS-AX maintained stable visual acuity and central subfield thickness for six months compared to those receiving Regeneron’s Eylea (aflibercept), which is the current standard of care.

CLS-AX reduced injection frequency by 84%, with 67% of patients requiring no additional injections before the mandatory re-dosing at six months. At the four-month mark, 90% of patients needed no further treatment. CLS-AX also demonstrated a positive safety profile, with no serious ocular or treatment-related adverse events.

The study enrolled 60 wet AMD patients who had previously used Eylea. They were randomised 2:1, with 40 patients receiving CLS-AX and 20 continuing on Eylea for 36 weeks. Eylea – a vascular endothelial growth factor (VEGF) inhibitor – secured approval from the US Food and Drug Administration (FDA) in August 2023 for wet AMD, diabetic macular oedema (DME), and diabetic retinopathy (DR).

Clearside’s CEO George Lasezkay said that the data supports advancing the CLS-AX wet AMD program into Phase III development and provides further evidence of the potential benefits of delivering medicines to the back of the eye using the SCS Microinjector. “We believe this data supports our goal to potentially provide a safe, convenient wet AMD treatment option with the advantage of a flexible maintenance dosing regimen between 3 to 6 months,” added Lasezkay.

In contrast, Eylea’s dosing regimen is every four weeks for the first three months, and every two months after that. According to GlobalData forecasts, Eylea is set to generate $1.96bn in 2030. If approved, CLS-AX could pull in up to $204m in the same year.

Clearside previously investigated CLS-AX in an open-label Phase I/IIa trial (NCT04626128) in wet AMD patients. The trial was followed up by an extension study (NCT05131646) where 15 of the participants were monitored for further six months after receiving a single dose of CLS-AX. The candidate met the primary endpoint of the Phase I/IIa trial, demonstrating a safety profile at all doses and time points. Two of the four cohorts showed signs of durability, biological effect, and a meaningful reduction in treatment burden.