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`OptometryTimesOptometryAlcon
`Shire gets FDA nod for Xiidra (lifitegrast) for dry eye
`
`July 15, 2016
`By Gretchyn M. Bailey, NCLC, FAAO, Editor in Chief, Content Channel Director
`
`Lexington, MA—Shire plc obtained U.S. Food and Drug Administration (FDA) approval for
`Xiidra (lifitegrast ophthalmic solution) 5%, a twice-daily eye drop indicated for the treatment of the
`signs and symptoms of dry eye disease in adult patients. Shire expects to launch Xiidra in the
`United States in the third quarter of 2016.
`
`Xiidra is the only prescription eye drop indicated for the treatment of signs and symptoms of dry
`eye. It joins Restasis (cyclosporine ophthalmic emulsion, Allergan) 0.05%, which since its launch in
`2003 had been the only prescription therapy for dry eye. Restasis is indicated to increase tear
`production in patients whose tear production is presumed to be suppressed due to ocular
`inflammation associated with keratoconjunctivitis sicca
`
` “The FDA’s approval of Shire's Xiidra is the biggest news to hit eye care in quite awhile and the
`biggest news in the dry eye arena in over a decade,” says Optometry Times Chief Optometric Editor
`Ernie Bowling, OD, FAAO. “After countless drugs failed to make it through the FDA pipeline, at
`long last we have another prescription medication for our dry eye patients. I look forward to
`offering this medication to my patients, many of whom have long suffered with this disease and
`have anticipated this drug’s approval.”
`
`According to Shire, about 16 million adults in the U.S. are diagnosed with dry eye disease.
`
`The company was expecting to hear from the FDA on July 23, which was the Prescription Drug
`User Fee Act (PDUFA) date—or deadline for the FDA to review a new drug application (NDA).
`
`http://optometrytimes.modernmedicine.com/optometrytimes/news/shire-gets-fda-nod-xiidra-lifitegrast-dry-eye
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`MYLAN - EXHIBIT 1078
`Mylan Pharmaceuticals Inc. et al. v. Allergan, Inc.
`IPR2016-01127, -01128, -01129, -01130, -01131, & -01132
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`Bob Dempsey, vice president and head of ophthalmics at Shire, says to have approval come early
`on July 11 was a tremendous accomplishment by the team and the FDA.
`
`“Xiidra is the first treatment to be approved for both signs and symptoms of dry eye disease,” he
`says. “To meet that extremely high bar is a tremendous accomplishment to address this very
`common condition.
`
`“I’ve been involved with Allergan, Inspire, Bausch + Lomb, and now Shire, with the trials and
`tribulations of the condition in that there’s a discordance of signs and symptoms—they often don’t
`run together. It can be a very different development path. It was enhanced by Shire’s entrance into
`the space. We looked at what had been done in previous research and looked at it through a
`different lens. Symptoms are what’s driving patients in to see the optometrist or ophthalmologist.”
`
`Newcomer vs. veteran
`
`Milton Hom, OD, FAAO, who consults with both Shire and Allergan and is an Optometry Times
`Editorial Advisory Board member, says that with any new drug comes a lot of questions.
`
`“In one corner, we have the proven option, Restasis. How does Xiidra compare with Restasis? Does
`Xiidra work for meibomian gland dysfunction? Should Xiidra be a first-line choice instead of
`artificial tears, or should it be a last resort? Is it compatible with Restasis or Lotemax (loteprednol
`0.5%, Bausch + Lomb)? How does it fit into the dry eye algorithm? Which patients does it work
`with? Which patients doesn’t it work with?”
`
`Dr. Hom says the industry should be prepared for a deluge of marketing information.
`
`“I think we are one the cusp of a huge marketing war between the new challenger and the veteran
`champion. It reminds me of the numbers war between Zymar (gatiifloxacin, Bausch + Lomb) and
`Vigamox (moxifloxacin, Alcon),” he says.
`
`“We were deluged with study after study showing differences between the two. This new war will
`have a different flavor. Instead of numbers, it will be an alphabet war: NFK-B, iCAM, LFA, T-cell,
`MMP-9, etc. It will be all about the intricacies of inflammation. People always want to simplify and
`simplify. If you think inflammation is complicated now, you ain’t seen nothing yet. The dialogue is
`going to be several levels higher in complexity.”
`
`However, he says that patients will benefit the most from a new development to treat dry eye.
`
`“And that’s the way it should be,” he says.
`
`ODs looking ahead to treating patients
`
`Paul Karpecki, OD, FAAO, was involved with lifitegrast studies OPUS-2, SONATA, and OPUS-3
`studies and says Xiidra shows great clinical efficacy with improvement in symptoms close to two
`weeks after therapy began. That improvement was maintained while patients remained on Xiidra. In
`addition, corneal staining improved after a month. Burning and/or abnormal taste (dysgeusia)
`occurred in about one in five patients—most cases were mild and transient.
`
`“I still have patients who say their eyes felt better while in the study (on study drug) than any other
`time,” he says.
`
`Dr. Karpecki is a clinical investigator and consultant for Shire.
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`http://optometrytimes.modernmedicine.com/optometrytimes/news/shire-gets-fda-nod-xiidra-lifitegrast-dry-eye
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`Page 3 of 3
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`Optometry Times Editorial Advisory Board member Ben Gaddie, OD, FAAO, says it’s a milestone
`to see another medication approved for the treatment of dry eye disease.
`
`“The novel mechanism of action for Xiidra builds on our anti-inflammatory armamentarium as
`another excellent option for the management of this debilitating condition,” he says. “I’m excited to
`gain some clinical experience with Xiidra and hope it will benefit my patients with dry eye disease.”
`
`Walt Whitley, OD, FAAO, Optometry Times Editorial Advisory Board member, was involved with
`OPUS-1 and OPUS-2 studies.
`
`“Many investigational drugs attempted but were unable to meet both primary endpoints for
`symptom and sign,” he says. “I think the biggest benefit of Xiidra will be for our patients—it will
`bring more awareness of dry eye disease, more options for treatment, and more opportunities to
`address this chronic condition which affects so many.”
`
`Dr. Whitley has received honoraria and funding for advisory board, research, and speaking.
`
`Looking at the science
`
`Xiidra is dosed twice per day, approximately 12 hours apart, in each eye. The safety and efficacy of
`Xiidra was studied in 1,181 patients (of which 1,067 patients received lifitegrast 5%) in four
`placebo-controlled 12-week trials. Each of the four studies assessed the effect of Xiidra on both the
`signs and symptoms of dry eye disease at baseline and Weeks Two, Six and 12. Assessment of
`symptoms was based on change from baseline in 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 all four studies, a larger reduction in EDS was observed with Xiidra at six and 12 weeks. In two
`of the four studies, an improvement in EDS was seen with Xiidra at two weeks. At Week 12, a
`larger reduction in ICSS favoring Xiidra was observed in three of the four studies. The most
`common adverse reactions reported in five to 25 percent of patients were instillation site irritation,
`altered taste sensation (dysgeusia), and reduced visual acuity.
`
`“The clinical program supporting the approval of Xiidra is the largest for an investigational-stage
`dry eye disease candidate to date, including more than 2,500 patients,” says Edward Holland, MD,
`professor of clinical ophthalmology at University of Cincinnati and a clinical trial investigator for
`Xiidra. “The clinical trial program design took into consideration many of the challenges of past dry
`eye research.”
`
`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. 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.
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`http://optometrytimes.modernmedicine.com/optometrytimes/news/shire-gets-fda-nod-xiidra-lifitegrast-dry-eye
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