The Effect of OTX-101 on Tear Production in Patients with Severe Tear-deficient Dry Eye Disease: A Pooled Analysis of Phase 2b/3 and Phase 3 Studies

Abstract

Purpose: Impaired tear production–a common sign of keratoconjunctivitis sicca (KCS)–is associated with qualitative or quantitative tear deficiency. OTX-101 0.09% is a novel, nanomicellar formulation of cyclosporine A approved in the US for increasing tear production in patients with KCS. We present a pooled analysis of the phase 2b/3 and phase 3 studies evaluating the effect of OTX-101 on tear production in a subgroup of patients with keratoconjunctivitis sicca with severely impaired tear production (Schirmer’s score <5 mm in either eye at baseline). Methods: In these randomized, double-masked studies, patients instilled 1 drop OTX-101 or vehicle per eye twice daily for 84 days. Pooled efficacy endpoints included percent (%) of patients with ≥10 mm change from baseline and mean change from baseline in Schirmer’s score at day 84. Pooled safety endpoints included adverse event monitoring. Results: Subgroup analyses included 133 and 113 patients receiving OTX-101 and vehicle, respectively. Mean baseline (BL) Schirmer’s score ± standard deviation was 2.7 ± 1.2 for OTX-101 and 2.5 ± 1.1 mm for vehicle (P = .3203). On day 84, number (%) of patients with ≥10 mm Schirmer’s score change from baseline was 30 (22.6%) and 12 (10.6%, P = .0168); mean change from baseline ± standard deviation was 5.5 ± 8.0 and 3.6 (6.0, P = .0405) mm for OTX-101 and vehicle, respectively. Adverse events were mostly mild and did not require treatment. Conclusion: OTX-101 administered twice daily for 84 days significantly improved tear production vs vehicle in patients with severely impaired tear production, as evidenced by significantly larger proportion of patients with ≥10 mm increases from baseline and higher mean change from baseline in Schirmer’s scores.