0.1% water-free cyclosporine solution superior to vehicle on ocular surface in dry eye disease: ESSENCE 2 trial.

Essence 2 randomized clinical trial found that usage of 0.1% water-free cyclosporine solution yielded superior results as it produced early therapeutic effects on the ocular surface when compared to vehicle in dry eye disease patients. The trial results confirmed the ESSENCE 1 trial results and were published in the journal JAMA Ophthalmology.  

Dry eye disease (DED) is one of the most common public health problems with a significant impact on vision-related quality of life and the well-being of patients. Inflammation and immunologic processes cause marked changes in the ocular surface and tear film parameters, accompanied by eye discomfort and blurred vision symptoms. But there is an outstanding requirement for medications with rapid onset of action and a good tolerability profile producing clinically meaningful improvements. 0.1% cyclosporine which is a potent anti-inflammatory and immunomodulatory drug has been studied in the ESSENCE 1 trial showing significant results. Hence researchers conducted a phase 3 trial called the ESSENCE 2 trial that confirm the efficacy, safety, and tolerability of cyclosporine, 0.1%, solution (CyclASol [Novaliq GmbH]) by applying twice daily in comparison with its novel water-free vehicle for the treatment of the signs and symptoms of DED. 

The study was carried out from December 5, 2020, to October 8, 2021, using CyclASol for the Treatment of signs and symptoms of Dry Eye Disease (ESSENCE-2) in phase 3, multicenter, randomized, double-masked, vehicle-controlled clinical study. Eligible participants with moderate to severe DED were randomly assigned 1:1 to the treatment groups following a 14-day run-in period with an artificial tear administered twice daily for 29 days. The primary endpoints were changes from baseline in total corneal fluorescein staining (tCFS; 0-15 National Eye Institute scale) and dryness score (0-100 visual analog scale) at day 29. Assessment of conjunctival staining, central corneal fluorescein staining, and tCFS responders was also done. 

Results: 

Nearly 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. There were 79 Asian (9.5 %), 108 Black (12.9%), and 635 White (76.1%) among the participants.There was a greater improvement in tCFS grade among the cyclosporine group than the vehicle group on day 29. The dryness score also improved from baseline in both groups: −12.2 points for cyclosporine and −13.6 points for the vehicle. Nearly 293 participants (71.6%) from the cyclosporine group and 236 (59.7%) in the vehicle group achieved clinically meaningful reductions of 3 grades or higher in tCFS. There was a greater improvement in symptoms at day 29 including dryness and blurred vision among the responders compared with non-responders. 

Thus, the ESSENCE 2 trial showed promising results with 0.1% water-free cyclosporine solution on the therapeutic effects on the ocular surface in DED patients compared with vehicle. 

Further reading: Akpek EK, Wirta DL, Downing JE, et al. Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease: The ESSENCE-2 Randomized Clinical Trial. JAMA Ophthalmol. Published online April 06, 2023. doi:10.1001/jamaophthalmol.2023.0709