Lifitegrast
{{Short description|Chemical compound}}
{{Use dmy dates|date=July 2023}}
{{Infobox drug
| image = Lifitegrast skeletal.svg
| alt =
| caption =
| pronounce =
| tradename = Xiidra
| Drugs.com = {{drugs.com|monograph|lifitegrast}}
| MedlinePlus = a616039
| pregnancy_AU = B1
| pregnancy_AU_comment =
| pregnancy_category=
| routes_of_administration = Eye drops
| ATCvet =
| ATC_prefix = S01
| ATC_suffix = XA25
| legal_AU = S4
| legal_AU_comment =
| legal_CA = Rx-only
| legal_CA_comment = {{cite web | title=Eye health | website=Health Canada | date=9 May 2018 | url=https://www.canada.ca/en/services/health/drug-health-products/drug-medical-device-highlights-2017/approved-drugs/eye-health.html | access-date=13 April 2024}}
| legal_DE =
| legal_NZ =
| legal_UK =
| legal_US = Rx-only
| legal_UN =
| legal_status =
| bioavailability =
| protein_bound =
| metabolism =
| metabolites =
| onset =
| elimination_half-life =
| duration_of_action =
| excretion =
| CAS_number = 1025967-78-5
| PubChem = 11965427
| DrugBank = DB11611
| ChemSpiderID = 10139520
| UNII = 038E5L962W
| KEGG = D10374
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 133023
| ChEMBL = 2048028
| synonyms = SAR-1118
| IUPAC_name = N-{[2-(1-Benzofuran-6-ylcarbonyl)-5,7-dichloro-1,2,3,4-tetrahydro-6-isoquinolinyl]carbonyl}-3-(methylsulfonyl)-L-phenylalanine
| C=29 | H=24 | Cl=2 | N=2 | O=7 | S=1
| smiles = CS(=O)(=O)c1cccc(c1)C[C@@H](C(=O)O)NC(=O)c2c(cc3c(c2Cl)CCN(C3)C(=O)c4ccc5ccoc5c4)Cl
| StdInChI=1S/C29H24Cl2N2O7S/c1-41(38,39)20-4-2-3-16(11-20)12-23(29(36)37)32-27(34)25-22(30)13-19-15-33(9-7-21(19)26(25)31)28(35)18-6-5-17-8-10-40-24(17)14-18/h2-6,8,10-11,13-14,23H,7,9,12,15H2,1H3,(H,32,34)(H,36,37)/t23-/m0/s1
| StdInChIKey = JFOZKMSJYSPYLN-QHCPKHFHSA-N
}}
Lifitegrast, sold under the brand name Xiidra ({{IPAc-en|ˈ|z|aɪ|d|r|ə}}{{cite web|url=https://www.novartis.us/sites/www.novartis.us/files/xiidra_ppi.pdf|title=Patient information: Xiidra® (ZYE-druh) (lifitegrast ophthalmic solution) 5% for topical ophthalmic use|publisher=Novartis|date=June 2020|access-date=5 February 2021}}), is a medication for the treatment of signs and symptoms of dry eye, a syndrome called keratoconjunctivitis sicca. Lifitegrast reduces inflammation by inhibiting inflammatory cell binding. It is often used as an alternative to ciclosporin (Ikervis, Restasis, Vevye, Verkazia or Cequa) for dry eye treatment including meibomian gland dysfunction and inflammatory dry eye.
Adverse effects
Common side effects in clinical trials were eye irritation, discomfort, blurred vision, and dysgeusia (a distortion of the sense of taste).Drugs.com: Patient information for {{drugs.com|parent|xiidra}}.
Pharmacology
Lifitegrast is supplied as an eye drop.
=Mechanism of action=
Lifitegrast inhibits an integrin, lymphocyte function-associated antigen 1 (LFA-1), from binding to intercellular adhesion molecule 1 (ICAM-1). This mechanism down-regulates inflammation mediated by T lymphocytes.{{cite journal | vauthors = Murphy CJ, Bentley E, Miller PE, McIntyre K, Leatherberry G, Dubielzig R, Giuliano E, Moore CP, Phillips TE, Smith PB, Prescott E, Miller JM, Thomas P, Scagliotti R, Esson D, Gadek T, O'Neill CA | display-authors = 6 | title = The pharmacologic assessment of a novel lymphocyte function-associated antigen-1 antagonist (SAR 1118) for the treatment of keratoconjunctivitis sicca in dogs | journal = Investigative Ophthalmology & Visual Science | volume = 52 | issue = 6 | pages = 3174–3180 | date = May 2011 | pmid = 21330663 | doi = 10.1167/iovs.09-5078 | doi-access = free }}
History
Lifitegrast was initially designed by Sunesis and developed by SARcode Bioscience{{cite journal | vauthors = Semba CP, Gadek TR | title = Development of lifitegrast: a novel T-cell inhibitor for the treatment of dry eye disease | journal = Clinical Ophthalmology | volume = 10 | pages = 1083–1094 | year = 2016 | pmid = 27354762 | pmc = 4910612 | doi = 10.2147/OPTH.S110557 | doi-access = free }} which was acquired by Shire in 2013,{{cite news |url= https://www.shire.com/en/newsroom/2013/march/shire-to-acquire-sarcode |title=Shire To Acquire Sarcode Bioscience, Expands Presence In Ophthalmology |date=25 March 2013 | work = Shire }} which submitted a new drug application to the US Food and Drug Administration (FDA) in March 2015. The FDA granted Shire a priority review a month later, and requested additional clinical data, which were supplied in January 2016; approval was granted on 11 July 2016.{{cite news|url=https://www.shire.com/newsroom/2016/july/9pks5v|title=FDA Approves Shire's Xiidra|date=11 July 2016}}{{cite web | work = Drugs.com | url = https://www.drugs.com/history/xiidra.html | title = Xiidra (lifitegrast) FDA Approval History }} Lifitegrast was approved by Health Canada in January 2018, and available in Canadian pharmacies as of March 2018.
Shire was acquired by Takeda Pharmaceutical Company in late 2018.{{cite web | url = https://www.takeda.com/newsroom/newsreleases/2019/takeda-completes-acquisition-of-shire-becoming-a-global-values-based-rd-driven-biopharmaceutical-leader/ | title = Takeda Completes Acquisition of Shire, Becoming a Global, Values-based, R&D-Driven Biopharmaceutical Leader | publisher = Takeda | date = 8 January 2019 }} In May 2019 Novartis reached an agreement to purchase the assets associated with lifitegrast. Novartis will pay Takeda an upfront payment of $3.4 billion, while the latter drugmaker is eligible for milestone payments of as much as $1.9 billion. Novartis noted that the drug amassed approximately $400 million in revenue in 2018.{{cite press release | url = https://www.novartis.com/news/media-releases/novartis-acquire-xiidra-expanding-front-eye-portfolio-and-strengthening-leadership-eye-care | title = Novartis to acquire Xiidra, expanding front-of-eye portfolio and strengthening leadership in eye care | work = Novartis | date = 9 May 2019 }} In 2023, Novartis sold the assets to Bausch + Lomb for $1.75 billion and eligible for an additional $750 million in payments linked to future sales for Xiidra as well as two pipeline assets.{{Cite news |date=30 June 2023 |title=Novartis Sells Eye Drugs to Bausch + Lomb for Up to $2.5 Billion |language=en |work=Bloomberg News |url=https://www.bloomberg.com/news/articles/2023-06-30/novartis-sells-eye-drugs-to-bausch-lomb-for-up-to-2-5-billion | vauthors = Pfanner E, Kresge N }}{{Cite news | vauthors = Furnas D |date=4 October 2023 |title=Bausch + Lomb closes $2.5B XIIDRA acquisition |url=https://njbiz.com/bausch-lomb-closes-2-5b-xiidra-acquisition/ |work=NJBIZ}}