A Phase 3, Randomized, Double-Masked Study of OTX-101 Ophthalmic Solution 0.09% in the Treatment of Dry Eye Disease

Goldberg, Damien F.; Malhotra, Ranjan; Schechter, Barry A.; Justice, Angela; Weiss, Sidney L; Sheppard, John D.

doi:10.1016/j.ophtha.2019.03.050

Cited by 67 publications

(84 citation statements)

References 11 publications

(19 reference statements)

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“…28 Phase 2b/3 and 3 clinical studies showed that twicedaily administration of OTX-101 0.09% was superior to vehicle in increasing tear production and improving ocular signs from baseline, including conjunctival and corneal staining in patients with KCS. 29,30 Importantly, improvement in these objective signs was seen at and after 4 weeks of therapy. 29,30 In a pooled analysis of phase 2b/3 and 3 trials, least square mean change from baseline for total corneal staining on day 28 was −0.9 and −0.5 for OTX-101 0.09% and vehicle, respectively (P = 0.0008).…”

Section: Available Ophthalmic Csa Formulationsmentioning

confidence: 93%

“…29,30 Importantly, improvement in these objective signs was seen at and after 4 weeks of therapy. 29,30 In a pooled analysis of phase 2b/3 and 3 trials, least square mean change from baseline for total corneal staining on day 28 was −0.9 and −0.5 for OTX-101 0.09% and vehicle, respectively (P = 0.0008). 31 Similarly, there was a significant reduction in total conjunctival staining from baseline (P = 0.0316) on day 28 compared with the vehicle.…”

Section: Available Ophthalmic Csa Formulationsmentioning

confidence: 93%

“…29,30,32 Instillation site pain was the most frequent AE (21.8% in OTX-101 0.09% group and 4.0% in vehicle group) and there were no serious AEs considered related to treatment. 29,30,32…”

Section: Available Ophthalmic Csa Formulationsmentioning

confidence: 96%

“…• Proportion of patients achieving meaningful improvement in OSDI scores and corneal staining were not statistically significant compared with the vehicle group 24,25 • High incidence of ocular discomfort and patient dissatisfaction 25 Aqueous nanomicellar OTX-101 0.09% (CEQUA™), aqueous nanomicellar solution 27,29,30 • Improved corneal staining at 4 weeks and conjunctival staining at 6 weeks compared with vehicle, with improvement persisting throughout the study 29,30 • Improved Schirmer's test scores compared with vehicle at 3 months 29,30 • Effect in severe forms of KCS is unknown 29,30 Formulations 43% of enrolled and treated patients experienced AEs and the most frequent ocular AEs were installation site reactions including burning and pain. 22 A cationic nanoemulsion (Ikervis ® ; Santen SAS, Evry, France) ( Table 1) was developed and approved by the European Medical Agency in 2015 for use in severe keratitis that has not improved despite the use of artificial tears.…”

Section: Available Ophthalmic Csa Formulationsmentioning

confidence: 99%

“…34 About 93% of enrolled patients on OTX-101 0.09% completed phase 2b/3 and 3 studies, and the withdrawal rate due to AEs was less than 4%. 29,30,32 Most of the treatment-emergent AEs that occurred with OTX-101 0.09% during the 3-month treatment period were mild or moderate in nature and resolved without any treatment. 29,30,32 Instillation site pain was the most frequent AE (21.8% in OTX-101 0.09% group and 4.0% in vehicle group) and there were no serious AEs considered related to treatment.…”

Section: Available Ophthalmic Csa Formulationsmentioning

confidence: 99%

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<p>A Review of Topical Cyclosporine A Formulations—A Disease-Modifying Agent for Keratoconjunctivitis Sicca</p>

Jerkins

Pattar

Kannarr

2020

OPTH

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Keratoconjunctivitis sicca (KCS) is a multifactorial disease characterized by tear hyperosmolarity, inflammation, and ocular surface damage. Cyclosporine A (CsA) is used as an effective disease-modifying agent to improve the signs and symptoms of KCS by reducing inflammation, which interferes with tear production. This review provides an overview of efficacy, safety, and limitations of currently marketed topical CsA formulations-including CsA ophthalmic emulsion, cationic nanoemulsion, and aqueous nanomicelles-and highlights newer technologies for controlled ocular delivery of CsA and their clinical implications. Long available emulsion formulations of CsA are oil-based and have several limitations, including slow onset of efficacy and low intraocular penetration and bioavailability. Aqueous CsA nanomicelle carriers produce rapid improvement in objective signs of KCS such as corneal and conjunctival staining as early as 4 weeks and have acceptable safety profiles. CsA formulations using semifluorinated alkanes or polyaphrons are currently in clinical development, having recently completed Phase 2 studies. Other carriers for CsA currently in the preclinical phase include microemulsions, polymeric aqueous and lyophilized micelles, and hydrogels; these novel formulations have yet to undergo clinical trials. Formulations that improve tissue availability of CsA may be beneficial in clinical practice by providing faster onset of relief and improving patient adherence.

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Section: Available Ophthalmic Csa Formulationsmentioning

confidence: 93%

Section: Available Ophthalmic Csa Formulationsmentioning

confidence: 93%

“…29,30,32 Instillation site pain was the most frequent AE (21.8% in OTX-101 0.09% group and 4.0% in vehicle group) and there were no serious AEs considered related to treatment. 29,30,32…”

Section: Available Ophthalmic Csa Formulationsmentioning

confidence: 96%

Section: Available Ophthalmic Csa Formulationsmentioning

confidence: 99%

Section: Available Ophthalmic Csa Formulationsmentioning

confidence: 99%

See 3 more Smart Citations

<p>A Review of Topical Cyclosporine A Formulations—A Disease-Modifying Agent for Keratoconjunctivitis Sicca</p>

Jerkins

Pattar

Kannarr

2020

OPTH

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Comparison of Sodium-Glucose Cotransporter 2 Inhibitors vs Glucagonlike Peptide-1 Receptor Agonists and Incidence of Dry Eye Disease in Patients With Type 2 Diabetes in Taiwan

Hung

Chang

et al. 2022

JAMA Netw Open

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ImportanceSodium-glucose cotransporter 2 (SGLT2) inhibitors have been found to improve low-grade systemic and tissue inflammation; however, the association between SGLT2 inhibitor use and the incidence of dry eye disease (DED) has not been explored.ObjectiveTo investigate the association between SGLT2 inhibitor use and dry eye disease in patients with type 2 diabetes (T2D).Design, Setting, and ParticipantsA retrospective cohort analysis of the largest multi-institutional electronic medical records database in Taiwan was conducted to identify patients with T2D newly receiving SGLT2 inhibitors or glucagonlike peptide-1 receptor agonists (GLP-1 RAs) from 2016 to 2018. Data analysis was performed from March 1 to May 31, 2022. Propensity scores with inverse probability of treatment weighting were generated to enable homogeneous comparisons between the 2 groups.ExposuresTreatment with SGLT2 inhibitors or GLP-1 RAs.Main Outcomes and MeasuresIncident dry eye disease, which was defined by clinical diagnoses, plus the related drug prescription. Cox proportional hazards regression models were used to estimate hazard ratios with 95% CIs for the risk of DED.ResultsA total of 10 038 and 1077 T2D patients newly receiving SGLT2 inhibitors (mean [SD] age, 59.5 [12.1] years; 5689 [56.7%] men) or GLP-1 RAs (mean [SD] age, 58.5 [41.2] years; 587 [54.5%] men), respectively, were included in the analysis. The incidence of DED was lower in patients newly receiving SGLT2 inhibitors (9.0 events per 1000 person-years) compared with those receiving GLP-1 RAs (11.5 events per 1000 person-years), yielding a hazard ratio of 0.78 (95% CI, 0.68-0.89). Subgroup analyses indicated that the lowered DED risks associated with SGLT2 inhibitors in patients with T2D were similar across different age, sex, blood glucose level, and kidney function groups. Results from the sensitivity analyses (including the propensity score–matching approach, on-treatment analyses, and different follow-up periods of 1, 2, and 3 years) were similar to the main analyses.Conclusions and RelevanceThe findings of this study suggest that patients with T2D newly receiving SGLT2 inhibitors may have a lower risk for DED compared with those receiving GLP-1 RAs. Prospective studies are needed to analyze these results.

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Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease

Akpek

Wirta

Downing³

et al. 2023

JAMA Ophthalmol

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ImportanceDry eye disease (DED) is a common public health problem with significant impact on vision-related quality of life and well-being of patients. Medications with rapid onset of action and a good tolerability profile remain an unmet need.ObjectiveTo assess efficacy, safety, and tolerability of a water-free cyclosporine ophthalmic solution, 0.1% (CyclASol [Novaliq GmbH]), applied twice daily in DED compared with vehicle.Design, Setting, and ParticipantsCyclASol for the Treatment of Signs and Symptoms of Dry Eye Disease (ESSENCE-2) was a phase 3, multicenter, randomized, double-masked, vehicle-controlled clinical study conducted from December 5, 2020, to October 8, 2021. Following a 14-day run-in period with an artificial tear administered 2 times per day, eligible participants were randomly assigned 1:1 to the treatment groups. Patients with moderate to severe DED were included in the study.InterventionsCyclosporine solution vs vehicle administered 2 times per day for 29 days.Main Outcomes and MeasuresThe primary end points were changes from baseline in total corneal fluorescein staining (tCFS; 0-15 National Eye Institute scale) and in dryness score (0-100 visual analog scale) at day 29. Conjunctival staining, central corneal fluorescein staining, and tCFS responders were also assessed.ResultsA total of 834 study participants were randomly assigned to cyclosporine (423 [50.7%]) or vehicle (411 [49.3%]) groups at 27 sites. Participants had a mean (SD) age of 57.1 (15.8) years, and 609 (73.0%) were female individuals. The majority of participants self-identified in the following race categories: 79 Asian (9.5 %), 108 Black (12.9%), and 635 White (76.1%). Participants treated with cyclosporine solution had greater improvement in tCFS (−4.0 grades) than the vehicle group (−3.6 grades) at day 29 (change [∆] = −0.4; 95% CI, −0.8 to 0; P = .03). The dryness score showed treatment benefits from baseline in both groups: −12.2 points for cyclosporine and −13.6 points for vehicle (∆ = 1.4; 95% CI, −1.8 to 4.6; P = .38). In the cyclosporine group, 293 participants (71.6%) achieved clinically meaningful reductions of 3 grades or higher in tCFS vs 236 (59.7%) in the vehicle group (∆ = 12.6%; 95% CI, 6.0%-19.3%; P &lt; .001). These responders showed greater improvement in symptoms at day 29 including dryness (∆ = −4.6; 95% CI, −8.0 to −1.2; P = .007) and blurred vision (Δ = −3.5; 95% CI, −6.6 to −4.0; P = .03) compared with nonresponders.Conclusions and RelevanceThe ESSENCE-2 trial confirmed that treatment with a water-free cyclosporine solution, 0.1%, results in early therapeutic effects on the ocular surface compared with vehicle. The responder analyses suggest that the effect is clinically meaningful in 71.6% of participants in the cyclosporine group.Trial RegistrationClinicalTrials.gov Identifier: NCT04523129

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A Phase 3, Randomized, Double-Masked Study of OTX-101 Ophthalmic Solution 0.09% in the Treatment of Dry Eye Disease

Cited by 67 publications

References 11 publications

<p>A Review of Topical Cyclosporine A Formulations—A Disease-Modifying Agent for Keratoconjunctivitis Sicca</p>

<p>A Review of Topical Cyclosporine A Formulations—A Disease-Modifying Agent for Keratoconjunctivitis Sicca</p>

Comparison of Sodium-Glucose Cotransporter 2 Inhibitors vs Glucagonlike Peptide-1 Receptor Agonists and Incidence of Dry Eye Disease in Patients With Type 2 Diabetes in Taiwan

Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease

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