ARVO 2023: Presentations highlight suprachoroidal injection delivery platform

Data from the company’s phase 1/2a OASIS trial in wet AMD showed that CLS-AX had an excellent safety profile and that Extension Study participants maintained their visual acuity while experiencing a meaningful reduction in treatment burden. (Image courtesy of Adobe Stock)

Clearside Biomedical Inc. announced today that several key poster presentations were delivered on the Company’s suprachoroidal injection delivery platform at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting in New Orleans.

George Lasezkay, PharmD., JD, president and CEO, noted the presentations at ARVO highlight the company’s efforts in suprachoroidal delivery of agents to the back of the eye.

“In the studies presented, SCS delivery of small molecule suspensions offered targeted, compartmentalized, and durable drug delivery to the chorioretina,” he said in a release. “In addition, our commercial partner presented data on the adoption of Xipere (triamcinolone acetonide injectable suspension) for suprachoroidal use, which continues to garner broad acceptance by the retinal community.”

Moreover, Lasezkay pointed out

“We are now looking to expand upon these results in ODYSSEY, our randomized, double-masked, Phase 2b clinical trial that we expect to initiate this quarter,” Lasezkay added.

In a presentation titled Safety and Tolerability Study of Suprachoroidal Injection of CLS-AX in Neovascular AMD Patients with Persistent Activity Following Anti-VEGF Therapy (OASIS, NCT04626128; Extension Study NCT05131646), Dennis M. Marcus, MD, of Southeast Retina Center, highlighted the results of OASIS, Clearside’s Phase 1/2a clinical trial in neovascular age related macular degeneration (wet AMD) with CLS-AX (axitinib injectable suspension).

According to Marcus, participants in the study had persistent, active disease and were heavily treatment experienced anti-VEGF sub-responders. CLS-AX administered via suprachoroidal (SCS) injection for was safe and well-tolerated in all cohorts.

The Extension Study in cohorts 3 and 4, exhibited early signs of durability and reduction in treatment burden with participants experiencing a 77% - 85% reduction in treatment burden. Importantly, a post hoc analysis of CLS-AX also showed a biologic effect at higher doses with stable best corrected visual acuity and central subfield thickness.

In a separate presentation by Viral Kansara, PhD, vice president, Preclinical Development, Clearside Biomedical, titled Suprachoroidal delivery of CLS-301, a potent small molecule integrin antagonist, offers multimonth durability and high bioavailability in the chorioretina, data assessed safety, durability and compartmentalization of a suprachoroidally administered small molecule suspension of a potent integrin antagonist (CLS-301) in a preclinical model.

Integrins play a major role in diverse biologic as well as pathologic processes such as cell adhesion/migration, angiogenesis, and immune responsiveness. The suspension was delivered using Clearside’s SCS Microinjector, an office-based procedure for SCS delivery.

In the study, SCS delivery of an integrin inhibitor was well tolerated and offered targeted, compartmentalized, and durable drug delivery to the chorioretina. This trend is consistent with other small molecule suspensions injected into the SCS. Further preclinical and clinical studies exploring long-term safety, pharmacology and toxicology of integrin inhibitors are warranted.

A third presentation, by lead authorPeter Yuwei Chang, MD, Massachusetts Eye Research and Surgery Institution, and titled Early Adoption of Triamcinolone Acetonide Suprachoroidal Injection for Uveitic Macular Edema: A Physician Survey, described retina/uveitis specialists who had completed at least 10 suprachoroidal injections of XIPERE and participated in virtual meetings in which they responded to 37 survey questions probing their experience.

The findings from the survey of early adopters of XIPERE suggest suprachoroidal injection was easy to learn and patient improvements in vision and macular edema aligned with findings in clinical registration trials.

According to the company, axitinib injectable suspension (CLS-AX) is an investigational proprietary suspension of axitinib for suprachoroidal injection. Axitinib is a tyrosine kinase inhibitor (TKI), currently approved as an oral tablet formulation to treat advanced renal cell carcinoma, that achieves pan-VEGF blockade, directly inhibiting VEGF receptors-1, -2, and -3 with high potency and specificity.

Moreover, the company maintains this broad VEGF blockade may have efficacy advantages over existing retinal therapies by acting at a different level of the angiogenesis cascade and may benefit patients who sub-optimally respond to current, more narrowly focused anti-VEGF therapies. Suprachoroidal injection of this proprietary suspension of axitinib has demonstrated meaningful potential in preclinical studies in multiple species and in a phase 1/2a wet AMD clinical trial, in which CLS-AX was well tolerated and demonstrated an excellent safety profile.

With suprachoroidal administration of axitinib, the company maintains there is the potential to achieve prolonged duration and targeted delivery to affected tissue layers. Clearside is developing CLS-AX as a long-acting therapy for the treatment of retinal diseases.

According to Clearside, OASIS was an open-label, single dose-escalation Phase 1/2a trial in wet AMD participants to assess the safety and tolerability of a single dose of CLS-AX administered by suprachoroidal injection via Clearside’s SCS Microinjector. Eligible participants were those who demonstrated stable visual acuity following two or more previous injections with an intravitreal anti-VEGF agent. All enrolled participants underwent diagnostic imaging on screening, followed by masked reading center confirmation of persistent active disease.

Moreover, the company noted participants from Cohorts 2, 3 and 4 who rolled over into the Extension Study were followed for a total of 6 months after a single dose of CLS-AX. Participants enrolled in OASIS were heavily anti-VEGF treatment experienced with active disease at screening, which was confirmed by an independent reading center.