Lifitegrast ophthalmic solution in the treatment of signs and symptoms of dry eye disease: design, development, and place in therapy

Morgan R Godin, Preeya K Gupta, Morgan R Godin, Preeya K Gupta

Abstract

A new topical ophthalmic medication, lifitegrast 5%, was recently approved by the US Food and Drug Administration for use in dry eye patients. Lifitegrast is an integrin antagonist that decreases inflammation on the ocular surface, thereby improving dry eye disease (DED). Through a series of prospective, multicenter, randomized, masked, placebo-controlled studies in >2,000 patients total, lifitegrast was shown to be effective for improvement in both the signs and symptoms of DED. A subsequent study focused on the safety profile of lifitegrast and demonstrated that the majority of adverse events were mild and resolved over time. Lifitegrast is now available for use in clinical practice.

Keywords: ICAM-1; LFA-1; OPUS-1; OPUS-2; OPUS-3; OSDI; SONATA; ocular surface.

Conflict of interest statement

Disclosure Dr Gupta is a consultant to Shire. Dr Godin does not have any conflicts of interest to report.

Figures

Figure 1
Figure 1
Timeline of lifitegrast studies. Notes: All OPUS studies were Phase III. Dates represent patient enrollment periods. The Phase II and OPUS-1 studies provided statistically significant evidence of improvement in a sign of dry eye due to lifitegrast; OPUS-2 and OPUS-3 provided evidence of improvement in a symptom of DED. All trials were conducted for 84 days in adult patients with DED. Abbreviation: DED, dry eye disease.

References

    1. Foulks GN, Jester JV, Murube J, et al. 2007 Report of the international dry eye workshop (DEWS) Ocul Surf. 2007;5(2):65–204.
    1. Li DQ, Chen Z, Song XJ, Luo L, Pflugfelder SC. Stimulation of matrix metalloproteinases by hyperosmolarity via a JNK pathway in human corneal epithelial cells. Invest Ophthalmol Vis Sci. 2004;45:4302–4311.
    1. Yeh S, Song XJ, Farley W, Li DQ, Stern ME, Pflugfelder SC. Apoptosis of ocular surface cells in experimentally induced dry eye. Invest Ophthalmol Vis Sci. 2003;44:124–129.
    1. Perez VL, Pflugfelder SC, Zhang S, Shojaei A, Haque R. Lifitegrast, a novel integrin antagonist for treatment of dry eye disease. Ocul Surf. 2016;14(2):207–215.
    1. Gao J, Morgan G, Tieu D, et al. ICAM-1 expression predisposes ocular tissues to immune-based inflammation in dry eye patient and Sjögrens syndrome-like MRL/lpr mice. Exp Eye Res. 2004;78(4):823–835.
    1. Semba CP, Gadek TR. Development of lifitegrast: a novel T-cell inhibitor for the treatment of dry eye disease. Clin Ophthalmol. 2016;10:1083–1094.
    1. Zhong M, Gadek TR, Bui M, et al. Discovery and development of potent LFA-1/ICAM-1 antagonist SAR 1118 as ophthalmic solution for treating dry eye. ACS Med Chem Lett. 2012;3(3):203–206.
    1. Lam H, Bleiden L, de Paiva CS, Farley W, Stern ME, Pflugfelder SC. Tear cytokine profiles in dysfunctional tear syndrome. Am J Ophthalmol. 2009;147:198–205.
    1. Gadek TR, Burdick DJ, McDowell RS, et al. Generation of an LFA-1 antagonist by the transfer of the ICAM-1 immunoregulatory epitope to a small molecule. Science. 2002;295:1086–1090.
    1. Rao VR, Prescott E, Shelke NB, et al. Delivery of SAR 1118 to the retina via ophthalmic drops and its effectiveness in a rat streptozotocin (STZ) model of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2010;51:5198–5204.
    1. Semba CP, Torkildsen GL, Lonsdale JD, et al. A phase 2 randomized, double-masked, placebo-controlled study of a novel integrin antagonist (SAR 1118) for the treatment of dry eye. Am J Ophthalmol. 2012;153(6):1050–1060.
    1. Sheppard JD, Torkildsen GL, Lonsdale JD, et al. Lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease: results of the OPUS-1 phase 3 study. Ophthalmology. 2014;121(2):475–483.
    1. Tauber J, Karpecki P, Latkany R, et al. Lifitegrast ophthalmic solution 5.0% versus placebo for treatment of dry eye disease: results of the randomized phase III OPUS-2 study. Ophthalmology. 2015;122(12):2423–2431.
    1. Holland EJ, Luchs J, Karpecki PM, et al. Lifitegrast for the treatment of dry eye disease: results of a phase III, randomized, double-masked, placebo-controlled trial (OPUS-3) Ophthalmology. 2017;124(1):53–59.
    1. Donnenfeld ED, Karpecki PM, Majmudar PA, et al. Safety of lifitegrast ophthalmic solution 5.0% in patients with dry eye disease: a 1-year, multicenter, randomized, placebo-controlled study. Cornea. 2016;35(6):741–748.

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