In 2018, Sun Pharmaceutical Industries Ltd. announced it received FDA approval for CEQUA™ (cyclosporine ophthalmic solution; OTX-101) 0.09% for the indication of dry eye disease (DED) and increasing tear production. CEQUA has the highest FDA-approved concentration of cyclosporine A and is the only cyclosporine A product that uses nanomicellar technology. This technology uses micelles to enter corneal and conjunctival cells, which enables the delivery of the higher concentrations of cyclosporine A.
Since then, it has completed a Phase 3 trial. The randomized, multicenter, vehicle-controlled, double-masked study included 744 patients (ages 18-90 years; 708 patients completed the study) enrolled in 45 sites across the US who were clinically diagnosed with DED, a global symptom score ≥40, and a lissamine green conjunctival staining score of ≥3 and ≤9 in at least 1 eye. Patients were randomized in a 1:1 ratio to twice-daily treatment with OTX-101 0.09% or vehicle for 84 days, and were required to show for five visits (screening, baseline, and three follow-up). The vehicle was identical to the OTX-101 0.09% formula but omitted the cyclosporine. Schirmer tests were performed at baseline and the final visit. Other end points assessed included corneal fluorescein staining, conjunctival lissamine staining, and the frequency and severity of dryness, irritation, or both using a modified Symptom Assessment In Dry Eye (SANDE) questionnaire.
Schirmer test scores were similar between groups at baseline (11.9 ± 7.8 mm for the OTX- 101 0.09% group and 12.1 ± 7.7 mm for the vehicle group). However, at the last visit, a higher percentage of eyes of patients in the OTX-101 0.09% group (16.6%) experienced a clinically significant improvement in Schirmer 2 tear test results (≥10 mm) compared with the vehicle group (9.2%); treatment difference between groups was statistically significant (95% confidence interval, 3.3%–11.3%; P < .001). Mean total conjunctival staining scores at baseline were 5.4 ± 1.7 and 5.5 ± 1.8 for the OTX-101 0.09% and vehicle groups, respectively. At the last visit, the OTX-101 0.09% group experienced a significantly greater improvement in total conjunctival staining than the vehicle group. However, improvements in total corneal staining were observed in both groups at the last visit; still the OTX-101 0.09% group experienced greater improvements than the vehicle group (P < .01).
Regarding patient-reported symptoms, there were no statistically significant differences in global symptom scores between groups at the last visit. Mean values for the global symptom scores, based on the modified SANDE questionnaire, were similar at baseline for the OTX-101 0.09% (63.1 ± 15.7) and vehicle (62.2 ± 16.1) groups. At the last visit, scores were –18.8 for the OTX-101 0.09% group and –19.1 for the vehicle group. OTX-101 0.09% was well tolerated by most patients. Most instances of ocular adverse events were of mild severity, such as burning or stinging after use; no abnormal changes in visual acuity were noted. In the OTX-101 0.09% group, 111 patients experienced a mild adverse event compared to 74 patients in the vehicle group. Overall, CEQUA 0.09% provides more than a 10-fold increase in aqueous solubility of cyclosporine and its demonstrated clinical improvement in DED supports its continued development as a treatment for DED.
References
Goldberg DF, Malhotra RP, Schechter BA, Justice A, Weiss SL, Sheppard JD. A phase 3, randomized, double-masked study of OTX-101 ophthalmic solution 0.09% in the treatment of dry eye disease. Ophthalmology. 2019;126(9):1230-1237. doi: 10.1016/j.ophtha.2019.03.050.
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