Shire plc announced that the US Food and Drug Administration (FDA) 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 3 study of lifitegrast, OPUS-3, that, if positive, will be the basis of Shire’s response to the CRL.

“We were disappointed, but will soon have data from the phase 3 study, OPUS 3,” said Flemming Ornskov, M.D., CEO, Shire.

“OPUS-3 has now been completed and top-line data are expected before the end of the year. If the study is positive, we plan to refile our liftegrast submission in the first quarter of 2016, and will remain on track for the planned lifitegrast launch next year. We are committed to working with FDA to expeditiously provide the evidence required to deliver a new prescription treatment option for the 29 million adults in the US living with the symptoms of this chronic and progressive disease. This is an area of unmet medical need for which there has been no new FDA-approved treatment in over a decade.”

The FDA also requested more information related to product quality, which Shire is confident it can address in the CRL response.

Symptoms of dry eye disease vary by patient, but typically may include eye dryness, overall eye discomfort, stinging, burning, a gritty feeling and episodes of blurred vision.

OPUS-3, a randomized, double-masked, 12-week phase 3 study enrolled 711 patients to evaluate the efficacy and safety of lifitegrast. The clinical trial’s primary endpoint is patient-reported symptom improvement as measured by the Eye Dryness Score EDS scale.

The new drug application for lifitegrast included data from four randomized, controlled clinical trials with more than 1,800 patients. These include one phase 2 study, two phase 3 efficacy and safety studies (OPUS-1 and OPUS-2), and one long-term phase 3 safety study (SONATA).

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 (IFN?, TNFa, IL-2) as well as inhibiting other pro-inflammatory cytokines: IL-1a, IL-1ß, IL-2, IL-4, IL-5, and IL-13), all of which are known to be associated with dry eye disease.

Dry eye is a multifactorial disease of the tears and ocular surface diagnosed by an eye care professional.  It is diagnosed based on patient reported symptoms, such as eye dryness, overall eye discomfort, stinging, burning, a gritty feeling and episodes of blurred vision as well as signs, which can be objectively measured by an eye care professional to determine the presence of dry eye disease (e.g., Schirmer test, corneal fluorescein staining, conjunctival lissamine green staining, and tear break-up time). Dry eye may be exacerbated by reduced blink rate caused by computer use, and environmental factors such as low humidity, wind, and sunlight, as well as allergies.  Associated with inflammation that may eventually lead to damage to the surface of the eye, dry eye is an often chronic and progressive ocular disease that is one of the most common complaints to eye care professionals.