Regulatory Decision Summary for Xiidra

The clinical efficacy and safety of Xiidra in the treatment of the signs and symptoms of dry eye disease (DED) were evaluated in a total of 2,247 subjects in four 12-week studies. Each study was a randomized, double-blind, placebo-controlled safety and efficacy study in subjects with DED. In addition, the longer-term safety of Xiidra was evaluated in a 12-month placebo-controlled study in subjects with DED. In all studies, subjects were randomized to Xiidra 5% or placebo in a 1:1 ratio.

In the 12-week studies, evidence of improvement in symptoms of DED was observed in all four studies and an improvement in signs was observed in three of the four studies. Eye Dryness Score (EDS, a measure of symptoms) was rated by patients using a visual analogue scale (0 = no discomfort, 100 = maximal discomfort) at each study visit. The average baseline EDS was between 40 and 70. A larger reduction in EDS favoring Xiidra was observed at Day 42 and Day 84. Inferior fluorescein corneal staining score (ICSS, a measure of DED signs; 0 = no staining, 1 = few/rare punctate lesions, 2 = discrete and countable lesions, 3 = lesions too numerous to count but not coalescent, 4 = coalescent) was recorded at each study visit. The average baseline ICSS was approximately between 1.8 and 2.4. At Day 84, a larger reduction in ICSS favoring Xiidra was observed in three studies.

Overall safety included 1,287 subjects exposed to 5% lifitegrast; a total of 170 subjects were exposed to lifitegrast 5% for at least 12 months. Adverse reactions, related to lifitegrast, include dysgeusia, reduced visual acuity, and instillation site reactions (itching, redness, pain and irritation). The treatment duration (12 weeks versus 1 year) did not affect the safety profile.

Clinical and non-clinical pharmacology studies showed minimal systemic absorption of lifitegrast following topical ocular application. The results of the nonclinical safety studies showed no significant adverse ocular or systemic toxicological findings in central nervous, cardiovascular or pulmonary functions, or evidence of genotoxicity.

A Risk Management Plan (RMP) for Xiidra (lifitegrast) was submitted by Shire Pharmaceuticals Inc. to Health Canada. Upon review, the RMP was considered to be acceptable. The RMP is designed to describe known and potential safety issues, to present the monitoring scheme and when needed, to describe measures that will be put in place to minimise risks associated with the product.

Based on the data reviewed, the benefit-risk assessment for Xiidra used in the treatment of the signs and symptoms of DED is considered to be positive.