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

KEYWORDS:

• OTX-101
• tear production
• keratoconjunctivitis sicca
• dry eye disease
• ocular drug delivery.

Acknowledgments

This study was sponsored and funded by Ocular Technologies, SARL (now a wholly owned subsidiary of Sun Pharmaceutical Industries), which participated in the design, conduct, monitoring, data collection, data management, and data analysis of the study. Writing and editorial support for manuscript preparation were provided by Jennifer Meyering RN, MS, CMPP, of AlphaBioCom, LLC, and funded by Sun Pharmaceutical Industries, Inc. All authors met the International Council of Medical Journal Editors criteria and received neither honoraria nor payment for authorship.

Disclosure statement

MT reports consultant fees from Bausch & Lomb; Eyevance; Iridex; Mallinkrodt; Shire; Sun Pharmaceutical Industries, Inc.; and Zeiss; speaker fees from Bausch & Lomb; Iridex; Lumenis; Mallinkrodt; Shire; Sun Pharmaceutical Industries, Inc.; and Zeiss; research fees from Bausch & Lomb; DigiSight; Dompé Farmaceitici; Iridex; Kala Pharmaceuticals; Lumenis; Magellan; Mallinkrodt; MIXTO Lasering; Ocular Tech; Oculos; Opternative; ReVitaLid; Shire; Sun Pharmaceutical Industries, Inc.; and Zeiss; and miscellaneous fees from MIXTO Lasering.

PG is a consultant to Allergan; Alcon; Aurea; Bausch & Lomb; Johnson & Johnson Vision; Kala Pharmaceuticals; Novartis; Ocular Science; RegGenRxTree; Shire; Sight Sciences; TearLab; TearScience; and Zeiss. BM is an employee of Sun Pharmaceutical Industries, Inc. PK reports consultant fees from Akorn, Alcon Labs, Aldeyra, Allergan/Abbvie, Azura Pharmaceuticals, Bausch + Lomb, BioTissue, BlephEx, Bruder Healthcare, Bruno Pharmaceuticals, Cambium Pharmaceuticals, Dompe, Eyedetec, Eyegate, Eyevance, Healthe, Imprimis, Johnson & Johnson Vision, Kala pharmaceuticals, KEPLR Vision, Konan Medical, Mallinckrodt, Neurolens, Novartis, Oasis Medical, Ocuphire, Ocular Sciences, Oculus, OcuMedic, Osmotica, Oyster Point, RegenerEyes, Science Based Health, Sentiss Pharmaceuticals, Sight Sciences, Silk Technologies, Sun Pharmaceutical Industries, Inc., Surface Pharmaceuticals, Tarsus Medical, TearClear, Visant Medical, Vital Tears

Additional information

Funding

This work was supported by Sun Pharmaceutical Industries, Inc.