Lifitegrast

Lifitegrast, sold under the brand name Xiidra (/ˈzaɪdrə/[1]), 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.[2] It is often used in conjunction with ciclosporin (Ikervis, Restasis, or Cequa) for dry eye treatment including meibomian gland dysfunction and inflammatory dry eye.

Lifitegrast
Clinical data
Trade namesXiidra
Other namesSAR-1118
AHFS/Drugs.comMonograph
MedlinePlusa616039
Pregnancy
category
  • AU: B1
Routes of
administration		Eye drops
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: ℞-only
Identifiers
IUPAC name
  • N-{[2-(1-Benzofuran-6-ylcarbonyl)-5,7-dichloro-1,2,3,4-tetrahydro-6-isoquinolinyl]carbonyl}-3-(methylsulfonyl)-L-phenylalanine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.245.695
Chemical and physical data
FormulaC29H24Cl2N2O7S
Molar mass615.48 g·mol−1
3D model (JSmol)
SMILES
  • CS(=O)(=O)c1cccc(c1)C[C@@H](C(=O)O)NC(=O)c2c(cc3c(c2Cl)CCN(C3)C(=O)c4ccc5ccoc5c4)Cl
InChI
  • InChI=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
  • Key:JFOZKMSJYSPYLN-QHCPKHFHSA-N

Adverse effects

Common side effects in clinical trials were eye irritation, discomfort, blurred vision, and dysgeusia (a distortion of the sense of taste).[3]

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.[2][4]

History

Lifitegrast was initially designed and developed by SARcode Bioscience[5] which was acquired by Shire in 2013,[6] 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.[7][8] 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.[9] 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.[10]

See also
  • Restasis (ciclosporin eye drops for keratoconjunctivitis sicca)

References
  1. "Patient information: Xiidra® (ZYE-druh) (lifitegrast ophthalmic solution) 5% for topical ophthalmic use" (PDF). Novartis. June 2020. Retrieved 2021-02-05.
  2. Tauber J, Karpecki P, Latkany R, Luchs J, Martel J, Sall K, et al. (December 2015). "Lifitegrast Ophthalmic Solution 5.0% versus Placebo for Treatment of Dry Eye Disease: Results of the Randomized Phase III OPUS-2 Study". Ophthalmology. 122 (12): 2423–31. doi:10.1016/j.ophtha.2015.08.001. PMID 26365210.
  3. Drugs.com: Patient information for xiidra.
  4. Murphy CJ, Bentley E, Miller PE, McIntyre K, Leatherberry G, Dubielzig R, et al. (May 2011). "The pharmacologic assessment of a novel lymphocyte function-associated antigen-1 antagonist (SAR 1118) for the treatment of keratoconjunctivitis sicca in dogs". Investigative Ophthalmology & Visual Science. 52 (6): 3174–80. doi:10.1167/iovs.09-5078. PMID 21330663.
  5. Semba CP, Gadek TR (2016). "Development of lifitegrast: a novel T-cell inhibitor for the treatment of dry eye disease". Clinical Ophthalmology. 10: 1083–94. doi:10.2147/OPTH.S110557. PMC 4910612. PMID 27354762.
  6. "Shire To Acquire Sarcode Bioscience, Expands Presence In Ophthalmology". 25 March 2013.
  7. "FDA Approves Shire's Xiidra". 11 July 2016.
  8. Drugs.com: Xiidra (lifitegrast) FDA Approval History
  9. "Takeda Completes Acquisition of Shire, Becoming a Global, Values-based, R&D-Driven Biopharmaceutical Leader". Takeda. January 8, 2019.
  10. "Novartis to acquire Xiidra, expanding front-of-eye portfolio and strengthening leadership in eye care". Novartis (Press release). May 9, 2019.
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