Efficacy And Safety Of A Water-Free Cyclosporine 0.1% Formulation For The Treatment Of Dry Eye Disease: Results From Two Randomized Controlled Studies Essence-1 And Essence-2

Dry 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 good safety profile remain an unmet need. The two ESSENCE studies were performed to assess the efficacy, safety, and tolerability of a novel water-free, preservative-free cyclosporine ophthalmic solution, 0.1%, for the treatment of signs and symptoms of DED.

ESSENCE-1 (NCT03292809) and ESSENCE-2 (NCT04523129) were pivotal multi-center, randomized, double masked, vehicle-controlled studies conducted at 9 and 27 investigational sites in North America, respectively. In ESSENCE-1 328 patients were randomly assigned (1:1) to receive either the active investigational product CyclASol or vehicle bilaterally twice-daily for 85 days. In ESSENCE-2 834 patients were randomly assigned (1:1) to receive either of these treatments for 29 days.

The primary sign end point was changes from baseline (CFB) in total corneal fluorescein staining (tCFS; NEI scale) at day 29 for both studies. The primary symptom end points were CFB in Ocular Surface Disease Index (OSDI; ESSENCE-1) and CFB in dryness score (visual analogue scale; ESSENCE-2) at day 29. Other key efficacy endpoints such as conjunctival staining and tCFS responders were assessed. Safety and tolerability assessments included adverse events (AEs), visual acuity, biomicroscopy, funduscopy, intraocular pressure and comfort scales.

Mean age was 61.4 years in ESSSENCE-1 and 57.1 years in ESSENCE-2. In both studies the majority were female (71.6% and 73%). The first tested primary sign endpoint was significantly different favoring CyclASol (ESSENCE-1: p = <.001; ESSENCE-2: p = .03), demonstrating superiority over vehicle. The proportion of the patients showing a clinically meaningful improvement of ≥ 3 grades in the tCFS score were high (52.9% and 71.2%) in the CyclASol groups and significantly higher than the proportion in the vehicle groups. Primary symptom endpoints showed statistically significant improvements from baseline without reaching statistical significance over vehicle. AE rate was low and balanced between treatment groups.

The ESSENCE-1 and ESSENCE-2 studies showed that treatment with a water-free cyclosporin solution, 0.1% consistently results in early therapeutic effects on the ocular surface compared with vehicle. The responder analyses suggest that the effect is clinically meaningful for the majority of patients in the cyclosporine group. The safety and tolerability profile of CyclASol was beneficial in both studies shown by low rates of installation site reactions and highly comfort ratings.