ESSENCE-2 Trial Confirms Efficacy of Cyclosporine Solution 0.1% for DED

Article

The ESSENCE-2 study reported superiority of the water-free cyclosporine ophthalmic solution to vehicle in tCFS score at day 29, confirming results from ESSENCE-1.

Esen K. Akpek, MD │ Johns Hopkins University

Esen K. Akpek, MD

Courtesy of Johns Hopkins University

New results from the phase 3 ESSENCE-2 trial indicated treatment with a water-free cyclosporine solution 0.1% has early therapeutic effects on the ocular surface in patients with moderate to severe dry eye disease (DED).1

In the multicenter clinical study, cyclosporine solution showed superiority to vehicle in total corneal fluorescein staining (tCFS) score at day 29, consistent with results from the ESSENCE-1 trial. The Wilmer Eye Institute investigative team, led by Esen K. Akpek, MD, observed a statistically significant onset of effect in tCFS at day 15, which they noted as significantly faster than reported results for other DED therapies.

“In the cyclosporine group, a greater proportion (71.6%) of participants were tCFS responders compared with the vehicle group (59.7%), and this difference was statistically significant,” they wrote.

The phase 2b/3 ESSENCE-1 study previously reported the effects of cyclosporine solution 0.1% on corneal and conjunctival staining. A second pivotal phase 3 study was conducted to confirm the efficacy, safety, and tolerability of the solution in comparison with a novel water-free vehicle for the signs and symptoms of DED. ESSENCE-2 was conducted at 27 clinical sites in the United States from December 2020 to October 2021.

Following a 14-day run-in period, participants with moderate to severe DED were randomly assigned to receive either cyclosporine, 0.1%, solution or vehicle and returned for a follow-up visit on day 15 ± 2 and day 29 ± 2. Over the treatment period, patients were dosed 1 single eye drop per eye twice daily for 29 consecutive days.

The primary efficacy measures at day 29 were changes from baseline in tCFS measured by the National Eye Institute scale (NEI scale; 0 – 15) and dryness score measured by visual analog scale (VAS; 0 – 100). A responder analysis for tCFS helped evaluate if the results were clinically meaningful, defining a responder as having an improvement of 3 grades or higher on the NEI scale.

The 27 clinical sites screened 1879 patients and enrolled 834, including 423 (50.7%) randomly assigned to the cyclosporine group and 411 (49.3%) to the vehicle group. Participants had a mean age of 57.1 years and 609 (73.0%) were female. A total of 79 patients self-identified as Asian (9.5%), while 108 (12.9%) identified as Black and 635 identified as White (76.1%).

Upon analysis, Akpek and colleagues found those treated with cyclosporine solution had a larger improvement in tCFS from baseline (–4.0 grades reduction) than the vehicle group (–3.6 grades reduction) at day 29 (change [Δ] = –0.4; 95% confidence interval [CI], –0.8 to 0; P = .03). Meanwhile, the dryness score was shown to improve from baseline in both groups, with –12.2 points for the cyclosporine group and –13.6 points for the vehicle group (Δ = 1.4; 95% CI, –1.8 to 4.6; P = .38).

The investigative team noted all secondary endpoints reported better outcomes with cyclosporine over vehicle, including central CFS, central CFS responders, conjunctival staining, and tCFS at day 15,. Data showed 293 participants (71.6%) achieved clinically meaningful reductions of 3 grades or higher in tCFS with cyclosporine versus 236 (59.7%) in the vehicle group (Δ = 12.6%; 95% CI, 6.0%-19.3%; P < .001).

Safety was similar between the 2 study groups, including the number of patients reporting at least 1 treatment-emergent adverse event (TEAE) or ocular TEAE. Additionally, installation-site reactions were low and eye drop comfort assessments were favorable between the 2 groups, with the tolerability profile potentially addressing an unmet need in DED therapy, according to Akpek and colleagues.

“Rapidity and the magnitude of improvements on the corneal epithelial damage are potential differentiators to existing therapies,” they added. “More data from clinical practice would be beneficial in understanding the potential of this treatment.”

References

  1. 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

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