Phase 3 Efficacy (Worse-Eye Analysis) and Long-Term Safety Evaluation of OTX-101 in Patients with Keratoconjunctivitis Sicca

John Sheppard, Mark Bergmann, Barry A Schechter, Jodi Luchs, Abayomi Ogundele, Paul Karpecki, John Sheppard, Mark Bergmann, Barry A Schechter, Jodi Luchs, Abayomi Ogundele, Paul Karpecki

Abstract

Background: OTX-101 is approved for treatment of keratoconjunctivitis sicca (KCS). We present results of a phase 3 worse-eye efficacy analysis and 1-year safety extension.

Methods: During the double-masked treatment phase, patients with bilateral KCS were randomized 1:1 to 12 weeks OTX-101 or vehicle 1 drop per eye twice daily. Efficacy assessments included Schirmer's test and corneal and conjunctival staining. All patients who completed the treatment phase were eligible for enrollment in the open-label extension and received 1 drop OTX-101 twice daily for up to 52 weeks. Safety endpoints included adverse event (AE) monitoring, Snellen visual acuity (VA), intraocular pressure (IOP), slit-lamp examination (SLE), and dilated fundoscopy.

Results: Overall, 745 and 258 patients enrolled in the treatment and safety extension phases, respectively. At 12 weeks, number (%) of patients with Schirmer's score increase of ≥10 mm from baseline was 76 (20.5%) vs. 42 (11.3%) for OTX-101 vs. vehicle (P=0.0005). OTX-101 significantly improved total conjunctival staining vs. vehicle at week 12 (least squares mean change from baseline -1.65 [0.12] vs. -1.12 [0.12], P=0.0013), and number (%) of patients with clear central corneas vs. vehicle at week 12 (222 [64.0%] vs. 199 [55.3%], P=0.0179). In the 1-year safety extension, AEs were mostly mild; instillation site pain was most common in 59 (22.9%) patients (17 [13.2%] vs. 42 [32.6%] patients receiving prior OTX-101 and vehicle). No safety concerns were raised by VA, IOP, SLE, and fundoscopy.

Conclusion: OTX-101 efficacy was confirmed in the eye with lower baseline Schirmer's score. OTX-101 was well tolerated long term.

Clinical trial: Registered at ClinicalTrials.gov on July 27, 2016. NCT02845674 https://ichgcp.net/clinical-trials-registry/NCT02845674?term=OTX-101&draw=2&rank=1.

Keywords: OTX-101; cyclosporine A; dry-eye disease; keratoconjunctivitis sicca; KCS.

Conflict of interest statement

JS reports personal fees from Allergan; Alcon/Novartis; Avedro; Bausch + Lomb; Clementia Pharma; EyeGate, Ocular Therapeutix; Science Based Health; Senju; Shire; Sun Pharmaceutical Industries, Inc.; TearLab; TearScience; Topcon; and TopiVert; and other fees from Alcon/Novartis, Kala Pharmaceuticals, Novaliq, Noveome, Ocular Therapeutix, Shire, and TearLab. MB receives fees from ICON Clinical Research, InSite Vision, Kala Pharmaceuticals, Oculos Clinical Research, RevitaLid, and Shire. BS receives fees from Johnson & Johnson; Shire; Valeant; and Sun Pharmaceutical Industries, Inc. JL receives personal fees from Alcon; Allergan; Bausch + Lomb; Eyevance, Icare, Shire; TearLab; and Sun Pharmaceutical Industries, Inc; and equity interest from Calhoun Vision, CLXO, Insightful Solutions, Ocular Sciences, Omega Ophthalmics, Trefoil Therapeutics, and RPS. AO is an employee of Sun Pharmaceutical Industries, Inc. PK reports consultant fees from Aerie; Akorn; Alcon; Allergan; Avellino Labs; Bausch & Lomb; Beaver Visitech; Bio-Tissue; Blephex; Bruder; Cambium; DGH Technology; EyeBrain/Neurolens; EyeGate Pharma; Eyevance; Focus Labs; Imprimis; Ivantis; Jobson Medical Information/Web MD; Johnson & Johnson Vision; Konan Medical; LensTech; Novartis; Oasis Medical; Ocular Sciences; Oculus; OcuMedic; OcuSoft; Oyster Point Medical; Reichert/Ametek; Science Based Health; Sentiss; Shire; Sight Sciences; Silk Technologies; Sun Pharmaceutical Industries, Inc.; Tarsus Medical; TearFilm Innovations; Tear Lab; Total Eyecare Partners; Topcon; Visant Medical; Visionix; and Vital Tears. The authors report no other conflicts of interest in this work.

© 2021 Sheppard et al.

Figures

Figure 1
Figure 1
Study design.
Figure 2
Figure 2
Patient disposition of the long-term safety phase.
Figure 3
Figure 3
Percentage of worse eyes with Schirmer’s score increase from baseline ≥10 mm at week 12. Analysis included 371 patients receiving OTX-101 and 373 patients receiving vehicle.
Figure 4
Figure 4
Least squares mean change from baseline in conjunctival staining in the worse eye for (A) total (temporal, nasal, and inferior zones), (B) temporal, (C) inferior temporal, (D) inferior nasal, and (E) nasal zones.
Figure 5
Figure 5
Percentage of worse eyes with complete clearing of the central cornea.

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