Lifitegrast Ophthalmic Solution 5.0% for Treatment of Dry Eye Disease: Overview of Clinical Trial Program

Abstract

Dry eye disease (DED) is a common inflammatory disorder of the ocular surface. Millions of people are affected by DED worldwide. Lifitegrast is a novel drug designed to inhibit DED-associated ocular inflammation. Four clinical trials have shown that lifitegrast is well tolerated and effective in improving symptoms and signs of DED over 12 weeks. A fifth trial showed long-term safety over 1 year. Lifitegrast has been in clinical use for more than one year in the United States and was recently approved in Canada (in December 2017). In this review, we discuss lifitegrast’s novel mechanism of action and provide an overview of its clinical trial program.

Establishment and application of a high-throughput screening model for cell adhesion inhibitors

“…Using the screening model, we obtained a potential cell adhesion inhibitor lifitegrast. And using the in vitro adhesion model, we verified that lifitegrast directly inhibited the cell adhesion between HUVEC and THP-1 cells, which is consistent with that lifitegrast blocks the interaction of LFA-1 with its cognate ligand ICAM-1 by binding to LFA-1 (Perez et al, 2016;Chan and Prokopich, 2019), further suggesting that the screening model is practicability. Although approved as a novel integrin antagonist, lifitegrast is used only for the treatment of the dry eye disease.…”

“…Frontiers in Pharmacology frontiersin.org with its cognate ligand ICAM-1 by binding to LFA-1 (Perez et al, 2016;Chan and Prokopich, 2019). Collectively, our results suggested that lifitegrast may directly interrupt the interactions between adhesion molecules on the surface of HUVEC and THP-1 cells and thus inhibit cell adhesion (Figure 3G).…”

“…Using this model, 2,791 compounds from the approved drug library and natural product library were tested, and 8 potential adhesion inhibitors were screened out (Table 3), which showed inhibitory activity against the cell adhesion between HUVEC and THP-1 cells at the drug concentration of 1.0 μM. Among which only lifitegrast, a drug for the treatment of dry eye (Chan and Prokopich, 2019), showed adhesion inhibition rate more than 50% and was comparable to that of cenicriviroc, which has the potential to be developed for the clinical treatment of other adhesion-related diseases.…”

Current Advances in Mechanisms and Treatment of Dry Eye Disease: Toward Anti-inflammatory and Immunomodulatory Therapy and Traditional Chinese Medicine

“…The binding of LFA-1 to ICAM-1 is known as the “immune synapse” and is the key step in T-cell activation. Lifitegrast is a new type of small molecule T lymphocyte inhibitor, which can effectively suppress the migration of APC, as well as the migration and recruitment of T lymphocytes to the ocular surface by inhibiting the interaction between LFA-1 and ICAM-1 ( 145 ). Lifitegrast is structurally similar to ICAM-1 and acts as a competitive antagonist to block LFA-1 and ICAM-1 binding and hence reduce the release of inflammatory factors ( 145 ).…”

“…Lifitegrast is a new type of small molecule T lymphocyte inhibitor, which can effectively suppress the migration of APC, as well as the migration and recruitment of T lymphocytes to the ocular surface by inhibiting the interaction between LFA-1 and ICAM-1 ( 145 ). Lifitegrast is structurally similar to ICAM-1 and acts as a competitive antagonist to block LFA-1 and ICAM-1 binding and hence reduce the release of inflammatory factors ( 145 ). Lifitegrast (5%) reduces dry eye scores and ocular discomfort with a good safety and tolerability profile ( 146 ).…”