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    Lifitegrast promising for patients using artificial tears

    Small-molecule integrin antagonist significantly reduced signs, symptoms in patients with dry eye disease

    Take home: John Sheppard, MD, highlights results of a phase III randomized, double-masked, placebo-controlled trial of lifitegrast in dry eye patients previously on artificial tears. He presented these results, a subset analysis of the OPUS-1 phase III trial, at the 2013 meeting of the American Society of Cataract and Refractive Surgery.

    Reviewed by John Sheppard, MD, MMSc

    Norfolk, VA—A small-molecule integrin antagonist designed to treat dry eye has shown statistically significant improvement in both the signs and symptoms of dry eye. The investigational agent, lifitegrast, blocks the chronic inflammation mediated by T-cells that is central to many forms of dry eye disease.

    More: How sleep patterns may affect MGD, dry eye

    “This is the latest in biotechnologically driven drug development custom created for a specific site and a specific condition, and it is showing very encouraging initial phase III clinical results,” said John Sheppard, MD, MMSc, president and partner, Virginia Eye Consultants, Norfolk, VA. “Dry eye is a very heterogeneous, multifactorial disease that has been surprising clinical investigators worldwide into remarkable frustration.”

    Dr. Sheppard presented the results of a subset analysis of the OPUS-1 phase III trial.

    New agents intended to treat dry eye face a particularly difficult regulatory hurdle with the FDA, Dr. Sheppard said. Dry eye products must demonstrate safety and efficacy against two distinct predetermined endpoints: a sign of dry eye and a symptom of dry eye. The only currently approved agent to treat dry eye, cyclosporine (Restasis, Allergan), was approved based upon statistically significant improvement in clinical signs of dry eye, but did not show a significant improvement in dry eye symptoms.

    Related: 3 steps to improve ocular health of dry eye patients

    What is unique about agent

    Lifitegrast is designed to immunomodulate a key pathway in the development and progression of dry eye. The inflammation associated with dry eye is largely mediated by T-cells which feature increased expression of intracellular adhesion molecule-1 (ICAM-1). Lifitegrast is an ICAM-1 decoy that blocks a key binding interaction between ICAM-1 and lymphocyte function-associated antigen-1 (LFA-1) expressed on the T cell surface. The blockade inhibits T-cell activation, adhesion, migration, proliferation and cytokine release in the eye, effectively down regulating inflammation and the resultant ocular surface disease.

    Lifitegrast is an aqueous, sterile, non-preserved and stable agent specifically designed to be delivered as an eye drop. An initial phase III study, OPUS-1, compared 5% lifitegrast with placebo. The active agent showed significant improvement of inferior and total corneal staining scores from baseline to week 12 (p = 0.0007 and p = 0.0148 respectively), meeting the signs criteria. The active agent also showed significant improvement in mean ocular discomfort score and eye dryness score at week 12 (p = 0.0273 and p = 0.0291 respectively).

    The problem, Dr. Sheppard explained, is that investigators had chosen improvement in the Ocular Surface Disease Index (OSDI) as the primary symptom endpoint. Though OSDI scores improved with lifitegrast, the improvement was not statistically significant.

    Related: How to manage cataracts with ocular surface disease

    “That’s like Babe Ruth saying, ‘I’m going to hit the ball over the left field fence,' and when he hits a home run over the right field fence, the umpire says it doesn’t count!” Dr. Sheppard said. “This is life with the regulatory process. You go back to the data.”

    Phase II data

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