Clearside Biomedical Features FDA-Approved Xipere in Multiple Presentations at AAO and American Uveitis Society Meetings
Clearside Biomedical announced that multiple presentations were given at the American Academy of Ophthalmology (AAO) 2021, which took place November 12-15, 2021 in New Orleans, LA.
“Our presentations at AAO and AUS, combined with the positive data presented by our partners and our ongoing interactions with the leaders in the retinal community, continue to demonstrate the benefits of suprachoroidal administration and the potential for physicians to adopt this procedure in their practices,” Thomas A. Ciulla, MD, MBA, Chief Medical Officer and Chief Development Officer, said in a company news release. “With the recent FDA approval of Xipere, we now have the first product approved for injection into the suprachoroidal space, and the first therapy approved for patients suffering from macular edema associated with uveitis. As a retinal physician, I am thrilled that my physician colleagues and their patients now have a new, innovative treatment option for those suffering from this serious, potentially blinding disease.”
Dr. Ciulla continued, “Importantly, our partners presented compelling data on the benefits of suprachoroidal delivery of their gene therapy and virus-like drug conjugate product candidates utilizing our SCS Microinjector. Regenxbio presented positive initial data from Cohort 2 of AAVIATE demonstrating that RGX-314 gene therapy was observed to be well tolerated with stable visual acuity and retinal thickness as well as a meaningful reduction in anti-VEGF treatment burden at 6 months in patients with wet AMD. In addition, further data from Cohort 1 in the phase 2 ALTITUDE trial for the treatment of diabetic retinopathy demonstrated stable visual acuity at three months after one-time treatment of RGX-314. And, Aura Biosciences presented safety results on AU-011, a virus-like drug conjugate for the treatment of choroidal melanoma, reporting that in the initial dose escalation cohorts preliminary results indicate a positive safety and tolerability profile for AU-011 delivered via suprachoroidal administration.”
Clearside AAO Presentations:
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 optical coherence tomography (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 is in press at the American Journal of Ophthalmology, a peer-reviewed Medline-indexed journal.
Title: Post-Hoc Analysis of Suprachoroidal CLS-TA vs. Rescue Therapies in Macular Edema associated with Noninfectious Uveitis
Lead Author: Christopher Henry, MD, FASRS
Conclusions: In this post hoc analysis of the PEACTHREE trial, visual function and safety outcomes of unrescued CLS-TA subjects were compared to rescued subjects in the control group reflecting current clinical treatment. Unrescued CLS-TA subjects experienced statistically significant greater mean reduction in central subfield thickness versus controls. Unrescued CLS-TA subjects also trended towards greater mean improvement in BCVA with approximately 52% of those subjects gaining ≥ 15 letters BCVA at 24 weeks versus 37% of subjects in the rescued control group. 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.
Title: Uveitic Macular Edema: Visual Function and Ocular Anatomy by Severity of Vision Loss
Lead Author: Ashvini Reddy, MD
Conclusions: This poster represented a post hoc analysis of the phase 3 PEACHTREE and AZALEA clinical trial patients who received triamcinolone acetonide injectable suspension for suprachoroidal use (SCS-TA). There were BCVA and anatomic benefits observed in patients who received SCS-TA at 24 weeks regardless of baseline BCVA status. A ceiling effect was observed in BCVA showing that patients with worse BCVA at baseline gained more letters over the 24 weeks than those with better BCVA at baseline. A floor effect was observed in retinal thickness demonstrating that the magnitude of change from baseline decreased as the retina approached normal thickness. Patients with worse BCVA at baseline experienced a greater reduction in CST.
Clearside American Uveitis Society Presentations:
In conjunction with the AAO meeting, Clearside participated in the American Uveitis Society Fall Meeting on Sunday, November 14, 2021.
Title: Suprachoroidal SCS-TA Safety and Efficacy in Macular Edema Associated with Uveitis: Post Hoc Analysis of Clinically Relevant Subgroups
Lead Author: Steven Yeh, MD
Conclusions: These post hoc analyses results corroborate the prospectively planned analyses for PEACHTREE. When unrescued SCS-TA patients are compared to rescued control patients, the analysis showed a significantly greater reduction in CST, a trend towards greater BCVA improvement, and a lower incidence of intraocular pressure elevation and cataract. The post hoc analysis represents a “real world” mix of rescue treatments, with limitations in terms of sample size and variable rescue treatment. The benefit of SCS-TA was noted regardless of administration of systemic corticosteroid or steroid-sparing therapy at baseline versus the control patients.
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 a fluid wave within the suprachoroidal space, underlying the retina. Imaging of suprachoroidal injections demonstrated 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.
Additional details on Clearside’s presentations can be accessed on the company’s website here.