Results of clinical trials with a novel RNA-based therapy (SYL1001) to treat patients with ocular pain associated to dry eye disease

Abstract

Purpose : To present the results of 2 dose-finding clinical trials (NCT01776658, EudraCT No: 2012-001177-93 & NCT02455999, EudraCT No: 2014-004857-15) to assess the safety and efficacy of SYL1001 in patients suffering of ocular pain associated to dry eye disease.

Methods : SYL1001 eye drops is a novel RNAi based drug in development by Sylentis. Two phase 2, multicenter, randomised, parallel groups, placebo-controlled, double-masked clinical trials have been run in parallel to evaluate the safety and efficacy of SYL1001. The primary objective was to compare the analgesic effect (VAS & OSDI scales) and ocular tolerance (Oxford scale & conjunctival hyperaemia) of 4 doses of SYL1001 after 10 days of treatment. The secondary objective was to assess the local (visual acuity, intraocular pressure (IOP), Schirmer’s test and tear break-up time (BUT)), systemic tolerance and adverse events (AEs) occurrence. Statistics: The Tukey or Wilcoxon method was used for pairwise comparisons between treatments, and the variable treatment was assessed using the ANOVA test. The level of statistical significance for all tests is set at p ≤ 0.05.

Results : A total of 127 patients were randomized into five arms (0.375%, 0.75%, 1.125% and 2.25% of SYL1001 q.d and Placebo (vehicle) q.d) in two clinical trials conducted in Spain and Estonia. All doses of SYL1001 reduced the VAS scale. The dose of 1.125% was significant better (p=0.016) than placebo. There were not significant differences in the OSDI value between placebo and SYL1001 groups after 10 days of treatment. The corneal staining indicated that the dose of 1.125% of SYL1001 was better tolerated than placebo. Safety results: No deaths, no unexpected or serious AEs related to SYL1001 have been reported. No statistical differences were found between the numbers of AEs reported in the SYL1001 groups and placebo. Vital signs, physical examination, biomicroscopy, ophthalmoscopy assessment and electrocardiogram did not show significant abnormalities.

Conclusions : Ocular pain is a high incidence disease with no specific treatments. SYL1001 is a new RNA based drug on development for the treatment of ocular pain associated to dry eye disease. The results of Phase 2 clinical trials indicate that SYL1001 is an ideal candidate for treating this pathology. Phase 3 results should confirm the promising results obtained in these clinical trials.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.