Shire is breathing a sigh of relief after the FDA approved its much-vaunted treatment for dry eye disease having previously rejected it late last year.
Xiidra is tipped to be a $1bn product and is one of the stars of the Ireland-based manufacturer’s pipeline.
The only prescription eye drop indicated for the treatment of both signs and symptoms of this condition, Xiidra (lifitegrast ophthalmic solution) is taken twice a day.
The FDA had insisted that an additional clinical trial was needed before Shire could re-apply for approval, delaying the medicine’s entry to the market.
But with the FDA green light now safely achieved, Shire expects to launch Xiidra in the US – where there are an estimated 16 million sufferers – in the third quarter of this year.
Allergan’s Restasis (cyclosporine ophthalmic emulsion) is the major player in dry eye disease – but Shire will hope that it can quickly establish a considerable foothold.
Shire CEO Flemming Ornskov said: “As Shire’s first FDA-approved medicine in ophthalmics, this significant milestone advances our goal of becoming the global leader in this category, where there are unmet patient needs.
“We have a robust ophthalmics pipeline, and we look forward to leveraging Xiidra as our entrée into the space as we continue to develop additional innovative eye care treatment options,” he adds.
Dry eye disease is caused by a reduced ability to produce tears and is characterised by red, painful eyes and vulnerability to infections.
The associated inflammation, which may eventually lead to damage to the surface of the eye, is thought to be primarily mediated by T-cells and associated cytokines.
One effect of this process may be increased expression of intracellular adhesion molecule-1 (ICAM-1); ICAM 1 may be overexpressed in corneal and conjunctival tissues in dry eye disease, Shire says.
Lifitegrast, which was licensed from SARcode Bioscience in 2013, is a small-molecule integrin antagonist that binds to the integrin lymphocyte function-associated antigen-1 (LFA-1), a cell surface protein found on leukocytes.
It blocks the interaction of LFA-1 with its cognate ligand intercellular adhesion molecule 1 (ICAM 1). LFA 1/ICAM 1 interaction can contribute to the formation of an immunological synapse resulting in T cell activation and migration to target tissues.
In vitro studies suggested that lifitegrast may inhibit T cell adhesion to ICAM 1 in a human T-cell line and secretion of inflammatory mediators (cytokines) in human peripheral blood mononuclear cells.
Shire admits that the exact mechanism of action of lifitegrast in dry eye disease is not known – but says that its OPUS-2 trial was the first study ever to show statistically significant improvement in symptoms of the disease.