Clearside Biomedical Delivers Podium and Poster Presentations at ASRS Annual Meeting
Clearside Biomedical announced that multiple presentations were given at the American Society of Retina Specialists (ASRS) Annual Meeting and at the OIS Retina Summit at ASRS, which took place October 7-12, 2021 in San Antonio, Texas.
“The data presented at both ASRS and last week’s Retina Society meetings continue to demonstrate that our proprietary in-office suprachoroidal space (SCS) injection treatment approach offers unprecedented targeted access to the back of the eye to treat a variety of serious retinal diseases,” said Thomas A. Ciulla, MD, MBA, Chief Medical Officer and Chief Development Officer. “Together with our partners, positive data has been presented utilizing our SCS Microinjector to deliver small molecules, gene therapy, and virus-like drug conjugates in multiple diseases, including uveitic macular edema, wet-AMD, diabetic retinopathy, and choroidal melanoma. We remain encouraged by these promising results as we continue to advance our own suprachoroidal clinical development programs and broaden our reach in other indications.”
Dr. Ciulla continued, “At ASRS, Regenxbio presented positive initial data from their ongoing Phase II ALTITUDE trial of RGX-314 for the treatment of diabetic retinopathy using our SCS Microinjector for in-office suprachoroidal delivery of their gene therapy. RGX-314 was well tolerated in 15 patients in Cohort 1 with no drug-related serious adverse events and no intraocular inflammation observed. It was also encouraging to see that there was a treatment effect after only three months. In addition, our partner Aura Biosciences presented their first data set on suprachoroidal delivery of AU-011, their novel virus-like drug conjugate for the treatment of primary choroidal melanoma, the most common intraocular tumor in adults. In their Phase 2 trial, there have been no treatment-related serious adverse events, dose limiting toxicities, or grade 3 adverse events observed thus far. This favorable safety profile to date may improve the therapeutic index, optimize treatment parameters and potentially lead to improved visual outcomes compared to intravitreal administration. These promising results presented by our partners further support our belief in the usefulness of our suprachoroidal injection platform and the SCS Microinjector with a wide variety of drug candidates.”
Preceding the ASRS meeting, Dr. Ciulla presented a corporate overview during the OIS Retina Summit highlighting the potential of suprachoroidal delivery, as well CLS-AX (axitinib injectable suspension), a proprietary suspension of axitinib, a potent pan-VEGF inhibitor, which is currently being evaluated in a Phase 1/2a clinical trial, entitled OASIS, for the treatment of wet age-related macular degeneration (AMD).
ASRS presentations were as follows:
Title: Suprachoroidal Administration of Small Molecule Suspensions:
Pre-Clinical Results Correlate to Clinical Trial Outcomes
Lead Author: James C Major, Jr., MD, PhD, FASRS
Conclusions: Multiple small molecule suspensions were evaluated in this study, including the corticosteroid triamcinolone acetonide, the tyrosine kinase inhibitor (TKI) axitinib, a complement inhibitor, and a plasma kallikrein inhibitor. Suprachoroidal delivery of these agents was investigated based on their potential for targeted delivery to affected tissues for efficacy, compartmentalization away from unaffected tissues for safety, and durability to address treatment burden. Optical coherence tomography (OCT) images demonstrated a definitive expansion of the suprachoroidal space both anteriorly and posteriorly to the optic nerve head just minutes after suprachoroidal injection. Suprachoroidal injection of small molecule concentrations were similar in both the retina and RPE/Choroid/sclera tissues. Favorable results from preclinical studies of a triamcinolone acetonide suspension (CLS-TA) translated to favorable clinical trial results for macular edema associated with non-infectious uveitis. There is potential for similar read-through of preclinical studies in the four current clinical trials enrolling patients utilizing suprachoroidal injection with the SCS Microinjector: CLS-AX (axitinib injectable suspension) for wet AMD; viral vector RGX-314 for wet AMD and diabetic retinopathy; and viral-like drug conjugate AU-011 for choroidal melanoma.
Title: Safety of the Suprachoroidal Injection Procedure Via Microinjector across Three Retinal Disorders
Lead Author: Allen Hu, MD
Conclusions: In this analysis, safety data from the day of the procedure was compiled from 621 patients (1,274 suprachoroidal injections) in eight clinical trials utilizing CLS-TA. The suprachoroidal injections were performed across three disease states: noninfectious uveitis, diabetic macular edema, and retinal vein occlusion. There were no serious adverse events (SAEs) involving lens injury, suprachoroidal hemorrhage, endophthalmitis, or retinal tears in any patient receiving one or more suprachoroidal injections. Three SAEs of interest in both the study and control arms were all deemed “not treatment related” by a masked investigator. Overall, the safety profile of the suprachoroidal injection procedure with a microinjector is not clinically meaningfully different than the intravitreal injection as reported in registration trials involving intravitreal anti-VEGF injections alone.
Title: Comparison of Suprachoroidal and Intravitreal Injection Flow Mechanics Analyzed via Multimodal Imaging
Lead Author: Shree Kurup, MD, FACP
Conclusions: This presentation compared suprachoroidal and intravitreal injections using several multimodal imaging diagnostics to demonstrate the injection flow differences between the two procedures. During an intravitreal injection, a bolus of dye was seen in the porcine vitreous cavity. In contrast, during a suprachoroidal injection, spreading of the dye was observed circumferentially and posteriorly towards the back of the eye, between the sclera and choroid. In the study, an endoscope was also placed within the vitreous cavity to film, in real time, both intravitreal and suprachoroidal injections. Suprachoroidal injection showed localized tissue depression, then expansion with no needle penetration through the choroid and retina. Imaging of suprachoroidal injections demonstrate acute opening of the suprachoroidal space, circumferential, posterior spread of injectate, and compartmentalization of injectate to posterior tissues. In summary, these multimodal imaging methodologies support the potential of suprachoroidal injections to target affected tissue layers in chorioretinal disorders.
Title: OCT Anatomic & Temporal Biomarkers in Uveitic Macular Edema
Lead Author: Dilraj S. Grewal, MD
Conclusions: In clinical practice, physicians often base treatment decisions on best corrected visual acuity (BCVA) and/or OCT assessment. There is limited information on longitudinal structure-function correlations in uveitic macular edema (UME). This study assessed these relationships, focusing on baseline anatomic features with potential prognostic value for visual response. This post hoc analysis of 198 eyes evaluated two Phase 3, 24 week UME clinical trials with CLS-TA (PEACHTREE and AZALEA). The study evaluated clinically relevant and prognostic relationships between BCVA and OCT-assessed features of macular edema including ellipsoid zone integrity, the presence and location of cystoid spaces, and the presence and location of subretinal fluid. Importantly, this analysis showed that eyes with early anatomic response demonstrated better BCVA response at 24 weeks, and that anatomic response may precede visual response in UME by one month or more among patients treated with CLS-TA. A manuscript describing these results has received favorable review in the American Journal of Ophthalmology, a prestigious peer-reviewed Medline-indexed journal.
Title: Post Hoc Analysis of Suprachoroidal CLS-TA versus Real World Rescue Therapies for Uveitic Macular Edema: Safety and Visual Function
Lead Author: Steven Yeh, M.D.
Conclusions: In this post hoc analysis of the PEACHTREE trial, visual function and safety outcomes of unrescued CLS-TA subjects were compared to rescued subjects in the control group. Unrescued CLS-TA subjects experienced statistically significant greater reduction in central subfield thickness and trended towards greater improvement in BCVA compared with control subjects rescued with therapies reflecting current clinical treatment. Suprachoroidally administered CLS-TA also appeared to be associated with a lower incidence of intraocular pressure-related safety findings. This post hoc analysis provides a comparison of CLS-TA to a “real world” mix of rescue treatments and corroborates the pre-specified endpoints of the Phase 3 PEACHTREE study. A manuscript describing these results is in press at Clinical and Experimental Ophthalmology, a peer-reviewed Medline-indexed journal.
Additional details on Clearside’s presentations can be accessed on the company’s website here.