Crisaborole

Last updated

Crisaborole
Crisaborole.svg
Clinical data
Pronunciation /juːˈkrɪsə/ yoo-KRIS-ə
Trade names Eucrisa, Staquis
Other namesAN-2728
AHFS/Drugs.com Monograph
MedlinePlus a617019
License data
Pregnancy
category
  • AU:B1
Routes of
administration 		Topical (ointment)
ATC code
Legal status
Legal status
  • CA: ℞-only
  • US: ℞-only
  • EU:authorization withdrawn on request of pharmaceutical company
  • In general: ℞ (Prescription only)
Identifiers
  • 4-[(1-Hydroxy-1,3-dihydro-2,1-benzoxaborol-5-yl)oxy]benzonitrile
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.225.309 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C14H10BNO3
Molar mass 251.05 g·mol−1
3D model (JSmol)
  • B1(c2ccc(cc2CO1)Oc3ccc(cc3)C#N)O
  • InChI=1S/C14H10BNO3/c16-8-10-1-3-12(4-2-10)19-13-5-6-14-11(7-13)9-18-15(14)17/h1-7,17H,9H2
  • Key:USZAGAREISWJDP-UHFFFAOYSA-N

Crisaborole, sold under the brand name Eucrisa among others, is a nonsteroidal topical medication used for the treatment of mild-to-moderate atopic dermatitis (eczema) in adults and children. [1] [2] [3] [4]

Contents

The most common side effects are reactions at the application site (including burning or stinging). [3]

Crisaborole is a phosphodiesterase 4 (PDE-4) inhibitor, although its specific mechanism of action in atopic dermatitis is not known. [1] [2]

Side effects

At the site of application, crisaborole may cause burning or stinging. Rarely, there may be an allergic reaction. [5]

Medical uses

In the US, crisaborole is indicated for topical treatment of mild to moderate atopic dermatitis in people three months of age and older. [2]

In the EU, crisaborole was authorized for treatment of mild to moderate atopic dermatitis in people two years of age and older with ≤ 40% body surface area (BSA) affected. [3]

Pharmacology

Pharmacodynamics

Crisaborole is a phosphodiesterase-4 inhibitor, mainly acting on phosphodiesterase 4B (PDE4B), which causes inflammation. [6] Chemically, crisaborole is a phenoxybenzoxaborole. [6] Inhibition of PDE4B appears to suppress the release of tumor necrosis factor alpha (TNFα), interleukin-12 (IL-12), IL-23 and other cytokines, proteins believed to be involved in the immune response and inflammation. [6]

People with atopic dermatitis produce high levels of cytokines, which can cause the inflammation of the skin seen in dermatitis. [3] Crisaborole blocks the release of certain cytokines involved in the inflammation process such as tumor necrosis factor alpha, interleukins (IL‑2, IL-4, IL-5), and interferon gamma. [3] By blocking their release, crisaborole is expected to ease the inflammation and therefore relieve symptoms of the disease. [3]

Chemistry

Crisaborole (chemical name: 4-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-5-yl)oxy]benzonitrile) is a member of the class of benzoxaboroles characterized by the presence of a boronic acid hemiester with a phenolic ether and a nitrile. [7] Crisaborole crystallizes into two polymorphs that differ in the conformation of the oxaborole ring. A cocrystal with 4,4'-bipyridine has been prepared and studied by X-ray crystallography. [8]

History

Crisaborole was developed by Anacor Pharmaceuticals for the topical treatment of psoriasis. [9] [6] [10] During preclinical and clinical development, crisaborole was called AN2728 and PF-06930164. [11] The drug was assumed to be potential $2bn-a-year blockbuster, when Pfizer acquired Anacor Pharmaceuticals. [12] However, the drug was commercially not successful, reaching only US$147 million in sales in 2018, and US$138 million in sales in 2019. [13]

Crisaborole was approved for use in the United States in December 2016 [14] [1] and for use in Canada in June 2018. [15]

The safety and efficacy of crisaborole were established in two placebo-controlled trials with a total of 1,522 participants ranging in age from two years of age to 79 years of age, with mild to moderate atopic dermatitis. [1] In both trials participants received treatment with either crisaborole or placebo twice daily for 28 days. [16] Neither the participants nor the health care providers knew which treatment was being given until after the trials were completed. [16] Overall, participants receiving crisaborole achieved greater response with clear or almost clear skin after 28 days of treatment. [1] [16] The trials were conducted in the US. [16]

Crisaborole, approved for the treatment of mild to moderate atopic dermatitis in the European Union, has been rapidly withdrawn from the European market (March 2020 - February 2022). [3]

See also

References

  1. 1 2 3 4 5 "FDA Approves Eucrisa for Eczema" (Press release). U.S. Food and Drug Administration (FDA). 14 December 2016. Archived from the original on 11 December 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  2. 1 2 3 "Eucrisa- crisaborole ointment". DailyMed. 21 April 2020. Retrieved 28 April 2020.
  3. 1 2 3 4 5 6 7 "Staquis EPAR". European Medicines Agency (EMA). 29 January 2020. Retrieved 28 April 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  4. ↑ He Y, Liu J, Wang Y, Kuai W, Liu R, Wu J (6 February 2023). Pimpinelli N (ed.). "Topical Administration of Crisaborole in Mild to Moderate Atopic Dermatitis: A Systematic Review and Meta-Analysis". Dermatologic Therapy. 2023: 1–9. doi: 10.1155/2023/1869934 . ISSN   1529-8019.
  5. ↑ "PRODUCT MONOGRAPH" (PDF). Government of Canada. 7 June 2018. Archived (PDF) from the original on 7 April 2019. Retrieved 7 April 2019.
  6. 1 2 3 4 Moustafa F, Feldman SR (May 2014). "A review of phosphodiesterase-inhibition and the potential role for phosphodiesterase 4-inhibitors in clinical dermatology" (PDF). Dermatology Online Journal. 20 (5): 22608. doi:10.5070/D3205022608. PMID   24852768.
  7. ↑ "WHO Drug Information, Vol. 29, No. 3, 2015. International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 74" (PDF). World Health Information. p. 391. Retrieved 26 April 2016.
  8. ↑ Campillo-Alvarado G, Didden TD, Oburn SM, Swenson DC, MacGillivray LR (2018). "Exploration of Solid Forms of Crisaborole: Crystal Engineering Identifies Polymorphism in Commercial Sources and Facilitates Cocrystal Formation". Crystal Growth & Design. 18 (8): 4416–4419. Bibcode:2018CrGrD..18.4416C. doi:10.1021/acs.cgd.8b00375. ISSN   1528-7483.
  9. ↑ Nazarian R, Weinberg JM (November 2009). "AN-2728, a PDE4 inhibitor for the potential topical treatment of psoriasis and atopic dermatitis". Current Opinion in Investigational Drugs. 10 (11): 1236–42. PMID   19876791.
  10. ↑ Spreitzer H (16 August 2016). "Neue Wirkstoffe: Crisaborol". Österreichische Apotheker-Zeitung (in German) (17/2016).
  11. ↑ "Crisaborole". AdisInsight. Retrieved 24 July 2017.
  12. ↑ "Pfizer to Acquire Anacor". Pfizer (Press release). 16 May 2016. Retrieved 28 April 2020.
  13. ↑ "Pfizer Financial Report" (PDF). Pfizer. Retrieved 9 April 2020.
  14. ↑ "Eucrisa (crisaborole) Ointment". U.S. Food and Drug Administration (FDA). 23 January 2017. Archived from the original on 8 August 2020. Retrieved 28 April 2020.
  15. ↑ "Eucrisa Regulatory Decision Summary". Health Canada. 23 October 2014. Archived from the original on 14 September 2019. Retrieved 14 September 2019.
  16. 1 2 3 4 "Drug Trials Snapshot: Eucrisa". U.S. Food and Drug Administration (FDA). 14 December 2016. Archived from the original on 27 September 2019. Retrieved 28 April 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
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