Date: 2015-10-27
Type of information: Results
phase: 3
Announcement: results
Company: Shire (UK - USA)
Product: lifitegrast
Action
mechanism: integrin antagonist. Lifitegrast, a small-molecule integrin antagonist, was designed in order to treat dry eye disease, and is a preservative-free topical eye solution. Lifitegrast is believed to work by reducing inflammation through inhibition of lymphocyte function-associated antigen 1 (LFA-1) and preventing its binding to intercellular adhesion molecule-1 (ICAM-1) that influences T-cell activation and cytokine (protein) release. The interaction between these two proteins plays a key role in the chronic inflammation associated with dry eye. T-cells are important components of the immune system that help control the body\'s response to a foreign or harmful substance or stimuli. Lifitegrast is Sarcode Bioscience lead product. Shire has purchased this company in March 2013.
Disease: dry eye disease
Therapeutic area: Ophtalmological diseases
Country: USA
Trial
details: The phase 3, multicenter, randomized, double-masked, and placebo-controlled study is evaluating the efficacy and safety of a 5.0% concentration of lifitegrast ophthalmic solution compared to placebo in subjects with dry eye disease and history of recent artificial tear use. (NCT02284516)
Latest
news: * On October 27, 2015, Shire announced positive topline results from OPUS-3, a phase 3 efficacy and safety study of lifitegrast versus placebo. These data showed OPUS-3 met the primary endpoint of significantly improving patient-reported symptoms of dry eye disease from baseline to day 84 (p=0.0007). Additionally, OPUS-3 met the secondary endpoints of symptom improvement from baseline to days 14 and 42 (p<0.0001 for both endpoints). Shire plans to use these data as part of the resubmission of the New Drug Application (NDA) for lifitegrast for the treatment of signs and symptoms for dry eye disease in the first quarter of 2016.
OPUS-3 compared lifitegrast to placebo administered twice daily for 84 days (12 weeks) in patients with dry eye, a recent history of artificial tear use within 30 days of study entry and an eye dryness score (EDS) ≥40. Lifitegrast met the single primary endpoint for patient-reported symptoms of eye dryness (mean change in Eye Dryness Score from baseline to week 12) (treatment difference of 7.16 [95% CI], 3.04, 11.28; p=0.0007). In OPUS-3, lifitegrast met the secondary endpoints of symptom improvement at Days 14 and 42 (treatment difference (95% CI) 7.85(4.33, 11.37) and 9.32 (5.44, 13.20) respectively, (p<0.0001)).
OPUS-3 topline results replicated the co-primary symptom endpoint of OPUS-2, a phase 3 efficacy and safety study (p<0.0001). OPUS-2 did not meet the co-primary endpoint for the sign of inferior corneal staining score, (p=0.6186).
OPUS-3 also evaluated the safety and tolerability of lifitegrast based on occurrence of treatment-emergent adverse events (TEAEs). The safety and tolerability profile of lifitegrast in OPUS-3 was consistent with previous studies involving lifitegrast. The most commonly reported TEAEs associated with lifitegrast were instillation site irritation (18.2% vs 3.1% for placebo), dysgeusia (altered sense of taste) (12.9 vs 0.3% for placebo) and instillation site reaction (12.6% vs 5.4%) for placebo. There were no ocular serious TEAEs or drug-related serious TEAEs. Additional data and analyses will be submitted for presentation at upcoming major medical meetings and will be submitted for publication in a peer-reviewed scientific journal.
Shire plans to use these data as part of the resubmission of the New Drug Application (NDA) for lifitegrast for the treatment of signs and symptoms for dry eye disease in the first quarter of 2016.
