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Suprachoroidal triamcinolone acetonide (CLS-TA, Clearside Biomedical) injection resulted in visual and anatomic improvements in eyes with diabetic macular edema, particularly in those that were treatment-naïve. Multiple injections of the investigational treatment were well-tolerated and associated with a low incidence of IOP elevation.
By Cheryl Guttman Krader;Reviewed by Charles C. Wykoff, MD, PhD
Results of a 6-month, phase I/II clinical trial demonstrate that suprachoroidal injection of preservative-free triamcinolone acetonide 4 mg using a proprietary microneedle (CLS-TA, Clearside Biomedical) is well-tolerated, and results in functional and anatomic improvements in eyes with diabetic macular edema (DME). The data also show greater benefit in treatment-naïve eyes, compared with those that were previously treated, reported Charles C. Wykoff, MD, PhD.
“The suprachoroidal route holds great promise for delivery of pharmaceuticals,” said Dr. Wykoff, director of research, Retina Consultants of Houston; deputy chairman of ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston. “For corticosteroids specifically, it may allow the drug level to be maximized in the retina and minimized in the anterior chamber with the potential to reduce cataract acceleration and the incidence of increased intraocular pressure (IOP).”
Dr. Wykoff added that the safety review from HULK study showed that multiple suprachoroidal CLS-TA injections were well tolerated and associated with a low incidence of elevated IOP.
HULK trial was an investigator-initiated multicenter trial that enrolled a total of 20 patients, of which 50% were treatment naïve and the other 50% had been previously treated. All treatment-naïve patients received intravitreal aflibercept 2 mg (Eylea, Regeneron) at baseline in addition to CLS-TA. The previously treated group had received an average of 23 prior treatments, which were comprised primarily of intravitreal injections with an anti-VEGF agent or corticosteroid, and received CLS-TA only.
Beginning at 2 months, all patients were eligible to receive suprachoroidal CLS-TA injection as needed (prn) if central retinal thickness (CRT) was >320 µm and not improved by at least 20% from the prior 2 visits.
At baseline, mean best corrected visual acuity (BCVA) was about 20/50 in both the treatment-naïve and previously treated arms. Mean CRT in the previously treated group was thicker than in the treatment-naïve eyes, 483 µm versus 442 µm.
The study had good retention and compliance. A single patient withdrew at month 4 and overall, less than 4% of scheduled visits were missed.
The eligibility criteria for retreatment were met for 53% of the 74 possible prn retreatments. In the previously treated and treatment-naive arms, retreatment was delivered for 61% and 44% of possible retreatments, respectively. Mean number of CLS-TA injections given over the 6-month trial was 3, and 50% of patients required either no or just 1 retreatment.
Mean change in BCVA from baseline to month 6 for the entire cohort was 5.2 letters. Subgroup analyses indicated that the improvement was driven by gains in the treatment-naïve arm that had an average gain of 8.5 letters compared with just 1.1 letters in the previously treated patients.
Mean CRT for the entire group decreased from 447 µm at baseline to 348 µm at 6 months.
“The trajectories of anatomic improvement were similar in the 2 study subgroups with all patients demonstrating anatomic improvement with suprachoroidal CLS-TA delivery,” Dr. Wykoff said. “At the end of 6 months, 89% of patients achieved a >50% reduction in excess CRT.”
Mean IOP was relatively stable across the 6-month trial with a slight increase of 1 mm Hg to 2.5 mm Hg seen at months 4 and 5. Two patients (10%), both in the previously treated arm experienced an IOP increase >10 mm Hg, and 15% of patients were started on topical IOP-lowering medication.
There were no serious ocular or systemic adverse events and no unexpected or new safety signals.
“Suprachoroidal CLS-TA has already completed other phase I and phase II trials, and there are multiple ongoing studies in phase II and phase III,” Dr. Wykoff said.
Discussing limitations of the study, Dr. Wykoff noted the small sample size and short duration of the HULK trial, along with the variable disease management received by patients in the previously treated arms and different treatment exposures for the 2 arms during the 6-month trial.
Charles C. Wykoff, MD, PhD
This article is based on a presentation given by Dr. Wykoff at the 2017 Retina Subspecialty Day prior to the 2017 American Academy of Ophthalmology meeting. Dr. Wykoff is a consultant to and receives grant support from Clearside Biomedical and from other companies that market or are developing treatments for DME. The HULK trial was supported by a grant from Clearside Biomedical.