Nanotechnology Delivers Cyclosporine for Dry Eye Disease
Ophthalmology, September 2019
Although cyclosporine ophthalmic emulsion 0.05% can increase tear production in patients with dry eye disease (DED), the hydrophobic nature of this drug limits its aqueous solubility in traditional preparations. Nanomiceller formulations enhance the solubility of hydrophobic agents by entrapping the drug within the micelle structures, thus creating a clear aqueous solution. OTX-101 0.09% is a nanomicellar solution of cyclosporine. In nonclinical pharmacokinetic studies, cyclosporine levels in ocular tissue were higher after administration of OTX-101 0.05% than after cyclosporine ophthalmic emulsion 0.05%. Goldberg et al. assessed the efficacy and safety of OTX-101 in a phase 3 randomized clinical trial and found the study drug to be superior to the vehicle control.
This multicenter double-masked trial included adults with a history and clinical diagnosis of DED who had a global symptom score of at least 40 and a lissamine green conjunctival staining score of ≥3 and ≤9 in at least one eye. Eligible enrollees had a run-in period of 14 to 20 days; during this time, they received vehicle twice daily.
Patients who remained eligible at baseline (day 0) were assigned randomly to receive twice-daily OTX-101 0.09% or vehicle for 84 days (n = 371 and 373, respectively). Efficacy was judged by evaluating patients’ signs and symptoms of DED and by Schirmer testing.
The primary efficacy endpoint was clinically meaningful improvement (≥10 mm) in the Schirmer test score from baseline to day 84. Safety was evaluated by documenting adverse events (AEs), monitoring visual acuity and intraocular pressure, and conducting slit-lamp, dilated ophthalmoscopy, and fundus examinations.
Schirmer scores demonstrated that the primary endpoint was achieved by day 84 in the active-treatment arm (p < .001 vs. vehicle). Greater improvement in corneal and conjunctival staining was seen in the treatment group. The global symptom score improved in all patients by approximately 30% with no difference between groups. OTX-101 0.09% was well tolerated, and most treatment-emergent AEs were mild. The most common ocular AE in both groups was mild stinging or burning after instillation of study medication. Differences between the OTX-101 and vehicle groups in multiple clinical signs were apparent within 28 days of starting treatment.
In summary, OTX-101 0.09% significantly improved tear production and ocular surface integrity.
The original article can be found here.