Ophthalmologists have been waiting more than a decade for a new treatment option for their dry eye patients-and the anticipation is finally over. Lifitegrast ophthalmic solution 5% (Xiidra, Shire Ophthalmics) is a twice-daily eye drop solution and is the only FDA-approved drug indicated to treat the signs and symptoms of dry eye disease, according to the company.
Editor's Update: Within weeks of its FDA approval, Shire's dry eye drug (Xiidra) is now available by prescription. With the availability of the drug, Shire has patient-focused resources to share information about prescription coverage and savings (subject to eligibility):
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Ophthalmologists have been waiting more than a decade for a new treatment option for their dry eye patients-and the anticipation is finally over.
Lifitegrast ophthalmic solution 5% (Xiidra, Shire Ophthalmics) is a twice-daily eye drop solution and is the only FDA-approved drug indicated to treat the signs and symptoms of dry eye disease, according to the company.
Signs of dry eye include inferior corneal staining which can be observed via slit lamp, whereas symptoms refer to the patient-reported discomfort associated with the disease. The symptoms are typically what drive patients to see an ophthalmologist in the first place.
Shire expects to launch the drug in the United States in the third quarter of 2016.
The last dry eye drug approval was for cyclosporine ophthalmic emulsion 0.05% (Restasis, Allergan) in 2003. However, cyclosporine functions to increase patients’ tear production, and did not have a specific indication for treating the signs and symptoms of dry eye, according to the FDA.
Lifitegrast is intended to help treat the estimated 16 million adults in the United States who have been diagnosed with dry eye. The chronic disease can eventually lead to eye surface damage and loss of visual function.
Learn more about the drug here.
"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,” said Flemming Ornskov, MD, MPH, chief executive officer of Shire. “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.”
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Shire will target that unmet need by “reaching out to both sides of the aisle” and approaching both optometrists and ophthalmologists equally to get the therapy to the patients who need it, said Robert Dempsey, vice president and head of ophthalmics at Shire.
“We are not going to just dip our toes in the water,” he said. “We are invested and committed.”
Dempsey noted the company’s investment speaks for itself: Shire has invested $800 million in acquisitions and building commercial, medical, and research/development infrastructure in the ophthalmic space.
Part of the reason the company was successful in bringing a new dry eye drug to the market was that it viewed the problem through a different lens, he said.
“We looked at it differently-not from ophthalmic standpoint, but drug delivery standpoint,” he said.
In coming years, Shire will explore life cycle management and alternative delivery options of the drug, he said.
“Dry eye is such an underappreciated problem,” said Edward Holland, MD, professor of clinical ophthalmology, University of Cincinnati, and clinical trial investigator for lifitegrast. He added it is rare for a medical disease to be so prevalent, but to have had only one treatment option.
In addition to the 16 million patients diagnosed with dry eye, Dr. Holland said another 35 to 40 million are undiagnosed with the condition.
Numerous studies have examined quality-of life (QOL) effects for dry eye patients and found that QOL scores were similar to patients with severe chest pain due to angina.
“Dry eye isn’t just an insignificant problem,” he said.
The clinical program for lifitegrast included more than 2,500 patients, making it the largest investigational-stage dry eye disease candidate in history, Dr. Holland said.
The safety and efficacy of the drug was studied in 1,181 patients (of which 1,067 received lifitegrast 5%) in four placebo-controlled, 12-week trials.
Learn more about the previous trials here.
Each of the studies assessed the drug’s effects at baseline, and at weeks 2, 6, and 12.
The assessment of symptoms change was based on the different from the baseline patient reported eye dryness score (EDS; 0-100 visual analogue scale). Assessment of signs was based on inferior corneal staining score (ICSS; 0-4 scale)
In each study, a larger reduction of EDS was observed with the drug at weeks 6 and 12.
In two of the four studies, an improvement in EDS was seen at 2 weeks for those taking lifitegrast. At week 12, a larger reduction in ICSS for patients treated with the drug was observed in three of the four studies.
The fact that the drug was significant at week 2 “was a pleasant surprise,” Dr. Holland said.
The most common adverse events reported in 5% to 25% of patients were instillation site irritation, altered taste sensation (dysgeusia), and blurred vision.
The company resubmitted its drug application in February 2016 after the FDA required another clinical study and additional product quality information in late 2015.
Dr. Holland said the agency’s initial rejection was not seen a negative response, and those at Shire were not discouraged because the FDA did not have the opportunity to analyze final data given the timing of the situation.
The inflammation associated with dry 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.
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Lifitegrast 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, and 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 demonstrated that lifitegrast may inhibit T-cell adhesion to ICAM-1 in a human T-cell line and may inhibit secretion of inflammatory mediators (cytokines) in human peripheral blood mononuclear cells. The exact mechanism of action of lifitegrast in dry eye disease is not known.
The drug has been approved for patients 18 years of age and older.