Abstract
Purpose :
To present the results obtained in phase 2 (SYL1001_II, NCT01776658, EudraCT No: 2012-001177-93) and phase 3 (HELIX, NCT03108664, EudraCT No: 2016-003903-79) clinical trials. These studies evaluated the safety and efficacy of tivanisiran against vehicle in patients with dry eye disease (DED).
Methods :
Tivanisiran sodium (former SYL1001) is a siRNA (small interfering ribonucleic acid) inhibitor of the Transient Receptor Potential cation channel subfamily V member 1 (TRPV1) synthesis. Both trials were multi-center, randomized, vehicle-controlled, conducted in two (SYL1001_II) and six (Helix) different countries including Spain, Estonia, Germany, Italy, Portugal and Slovakia. Tivanisiran sodium or placebo were administered as preservative-free eye drops, once daily for 10 days or 28 days, respectively. The primary outcomes were the change from baseline in Visual Analogue Scale (VAS) for eye discomfort/pain, Corneal Fluorescein Staining (CFS) and conjunctival hyperemia. The secondary outcomes were the effect of treatment on Tear Break Up Time (TBUT), Schirmer test and quality of life questionnaires. Objectives also consisted in the evaluation of local and systemic tolerability, and adverse event (AE) occurrence
Results :
SYL1001_II identified the dose of 1.125% as the most efficient one to reduce VAS score compare with placebo (-1.73 ± 0.32 vs. -0.91 ± 0.34, p = 0.013). Tivanisiran 1.125% improved conjunctival hyperemia in 50% of patients compared to 20% for placebo (p<0.05). CFS and TBUT also showed a numerical greater mean improvement from baseline. In Helix study, 330 patients were enrolled and 289 randomized after completing a run-in phase. The end of recruitment period was achieved on 4Q 2018. High overall compliance was detected, with only 18 related AEs, all were of mild to moderate intensity. No unexpected or serious related AEs have occurred, suggesting excellent local and systemic tolerability
Conclusions :
Phase II trials for tivanisiran 1.125% showed a significant improvement in VAS for ocular discomfort/pain and conjunctival hyperemia; the phase III trial confirmed the safety profile and will further document the effect of tivanisiran on this disease. Up to date, few therapeutic options are available and tivanisiran represents a new class of drugs for patients suffering from DED.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.