Shire Receives Complete Response Letter for Dry-Eye DrugBy
Shire reports that the US Food and Drug Administration (FDA) has requested an additional clinical study as part of a Complete Response Letter (CRL) to the company's new drug application for lifitegrast for the signs and symptoms of dry eye disease in adults. Shire has recently completed a Phase III study of lifitegrast, OPUS-3, that, if positive, will be the basis of Shire's response to the CRL. The FDA also requested more information related to product quality, which Shire said it is confident it can address in the CRL response.
In May 2014, Shire established its Ophthalmics Business Unit, where the company is focused on continuing to expand its ophthalmics portfolio to include treatment options for rare diseases and those for anterior and posterior eye conditions. Over the last two years, the company has made acquisitions that include Foresight Biotherapeutics, SARcode Bioscience, Premacure AB, and BIKAM Pharmaceuticals, which have helped bolster Shire's early-, mid- and late-stage ophthalmics pipeline. The company currently has an ophthalmics pipeline of investigational candidates in dry eye disease, retinopathy of prematurity, autosomal dominant retinitis pigmentosa, glaucoma, and infectious conjunctivitis.
Lifitegrast binds to the integrin lymphocyte function-associated antigen-1 (LFA-1), a cell surface protein found on leukocytes and blocks the interaction of LFA-1 with its cognate ligand intercellular adhesion molecule-1 (ICAM-1). ICAM-1 is over-expressed in corneal and conjunctival tissues in dry eye disease. LFA-1/ICAM-1 interaction contributes to formation of an immunological synapse resulting in T-cell activation and migration to target tissues. In vitro studies have demonstrated that lifitegrast inhibits T-cell adhesion to ICAM-1 expressing cells and inhibits secretion of key inflammatory cytokines (IFNÎ³, TNFÎ±, IL-2) as well as inhibiting other pro-inflammatory cytokines: IL-1Î±, IL-1Î², IL-2, IL-4, IL-5, and IL-13), all of which are known to be associated with dry eye disease.