Abrocitinib

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Abrocitinib
Abrocitinib.svg
Names
Trade namesCibinqo
Other namesPF-04965842
Clinical data
Drug classJanus kinase inhibitor[1]
Main usesAtopic dermatitis (eczema)[2]
Side effectsNausea, headache, herpes simplex, urinary tract infection, acne, impetigo, low platelets.[1]
Routes of
use
By mouth
Typical dose100 to 200 mg OD[1][2]
External links
AHFS/Drugs.comMonograph
Legal
License data
Legal status
Pharmacokinetics
Elimination half-life2.8–5.2 h
Excretion1.0–4.4% unchanged in urine
Chemical and physical data
FormulaC14H21N5O2S
Molar mass323.42 g·mol−1
3D model (JSmol)
  • CCCS(=O)(=O)NC1CC(N(C)c2ncnc3[nH]ccc23)C1
  • InChI=1S/C14H21N5O2S/c1-3-6-22(20,21)18-10-7-11(8-10)19(2)14-12-4-5-15-13(12)16-9-17-14/h4-5,9-11,18H,3,6-8H2,1-2H3,(H,15,16,17)/t10-,11+ checkY
  • Key:IUEWXNHSKRWHDY-PHIMTYICSA-N checkY

Abrocitinib, sold under the brand name Cibinqo, is a medication used to treat atopic dermatitis (eczema).[2] It may be used in cases that do not improve with other treatments.[1] It is taken by mouth.[1]

Common side effects include nausea, headache, herpes simplex, urinary tract infection, acne, impetigo, and low platelets.[1] Other side effects may include infections, sudden cardiac death, pulmonary embolism, and cancer.[1] Safety in pregnancy is unclear.[1] It is a Janus kinase inhibitor.[1]

Abrocitinib was approved for medical use in Europe in 2021 and the United States in 2022.[2][1] In the United Kingdom 4 weeks of treatments cost the NHS about £900 as of 2021.[4] In the United States this amount costs about 4,600 USD as of 2022.[5]

Medical uses

Abrocitinib is indicated for the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy.[2] It results in an improvement in 38 to 70% of people as opposed to 8 to 27% of people with placebo.[2]

Dosage

It is generally taken at a dose of 100 mg once per day.[1] Doses may be increased up to 200 mg once per day.[1] In those with kidney problems a starting dose of 50 mg once per day may be used.[1]

Side effects

The most common side effects are upper respiratory tract infection, headache, nausea, and diarrhea.[6]

Pharmacology

Mechanism of action

It is a selective inhibitor of the enzyme janus kinase 1 (JAK1).[6]

Pharmacokinetics

Abrocitinib is quickly absorbed from the gut and generally reaches highest blood plasma concentrations within one hour. Only 1.0 to 4.4% of the dose are found unmetabolized in the urine.[7]

History

It was developed by Pfizer.[2]

  • April 2016: initiation of Phase 2b trial
  • December 2017: initiation of JADE Mono-1 Phase 3 trial[8]
  • May 2018: Results of Phase 2b trial posted
  • October 2019: Results of Phase 3 trial presented[9]
  • June 2020: Results of second Phase 3 trial published[10]

Society and culture

Legal status

In October 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Cibinqo, intended for the treatment of atopic dermatitis.[11] The applicant for this medicinal product is Pfizer Europe MA EEIG.[11] In December 2021, the European Commission approved abrocitinib for the treatment of atopic dermatitis.[2][12]

In January 2022, the United States Food and Drug Administration (FDA) approved abrocitinib for adults with moderate-to-severe atopic dermatitis.[13]

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 "Cibinqo- abrocitinib tablet, film coated". DailyMed. 15 February 2022. Archived from the original on 3 March 2022. Retrieved 3 March 2022.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 "Cibinqo EPAR". European Medicines Agency (EMA). 11 October 2021. Archived from the original on 18 December 2021. Retrieved 17 December 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  3. "Cibinqo Product information". Health Canada. 25 April 2012. Archived from the original on 10 December 2022. Retrieved 30 September 2022.
  4. "Abrocitinib". SPS - Specialist Pharmacy Service. 24 January 2018. Archived from the original on 5 July 2022. Retrieved 11 December 2022.
  5. "Cibinqo". Retrieved 11 December 2022.
  6. 6.0 6.1 Gooderham MJ, Forman SB, Bissonnette R, Beebe JS, Zhang W, Banfield C, et al. (October 2019). "Efficacy and Safety of Oral Janus Kinase 1 Inhibitor Abrocitinib for Patients With Atopic Dermatitis: A Phase 2 Randomized Clinical Trial". JAMA Dermatology. 155 (12): 1371–1379. doi:10.1001/jamadermatol.2019.2855. PMC 6777226. PMID 31577341.
  7. Peeva E, Hodge MR, Kieras E, Vazquez ML, Goteti K, Tarabar SG, et al. (August 2018). "Evaluation of a Janus kinase 1 inhibitor, PF-04965842, in healthy subjects: A phase 1, randomized, placebo-controlled, dose-escalation study". British Journal of Clinical Pharmacology. 84 (8): 1776–1788. doi:10.1111/bcp.13612. PMC 6046510. PMID 29672897.
  8. Clinical trial number NCT03349060 for "Study to Evaluate Efficacy and Safety of PF-04965842 in Subjects Aged 12 Years And Older With Moderate to Severe Atopic Dermatitis (JADE Mono-1)" at ClinicalTrials.gov
  9. "Pfizer Presents Positive Phase 3 Data at the 28th Congress of the European Academy of Dermatology and Venereology for Abrocitinib in Moderate to Severe Atopic Dermatitis". Drugs.com. 12 October 2019. Archived from the original on 31 March 2022. Retrieved 4 November 2022.
  10. Silverberg, J. I.; Simpson, E. L.; Thyssen, J. P.; Gooderham, M.; Chan, G.; Feeney, C.; Biswas, P.; Valdez, H.; Dibonaventura, M.; Nduaka, C.; Rojo, R. (3 June 2020). "Efficacy and Safety of Abrocitinib in Patients With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial". JAMA Dermatology. 156 (8): 863–873. doi:10.1001/jamadermatol.2020.1406. PMC 7271424. PMID 32492087.
  11. 11.0 11.1 "Cibinqo: Pending EC decision". European Medicines Agency. 15 October 2021. Archived from the original on 15 October 2021. Retrieved 15 October 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  12. "European Commission Approves Pfizer's Cibinqo (abrocitinib) for the Treatment of Adults with Moderate-to-Severe Atopic Dermatitis". Pfizer Inc. (Press release). 10 December 2021. Archived from the original on 17 December 2021. Retrieved 17 December 2021.
  13. "U.S. FDA Approves Pfizer's Cibinqo (abrocitinib) for Adults with Moderate-to-Severe Atopic Dermatitis". Pfizer Inc. (Press release). 14 January 2022. Archived from the original on 16 January 2022. Retrieved 16 January 2022.

External links

External sites:
Identifiers:
  • Clinical trial number NCT03349060 for "Study to Evaluate Efficacy and Safety of PF-04965842 in Subjects Aged 12 Years And Older With Moderate to Severe Atopic Dermatitis (JADE Mono-1)" at ClinicalTrials.gov
  • Clinical trial number NCT03575871 for "Study Evaluating Efficacy and Safety of PF-04965842 in Subjects Aged 12 Years And Older With Moderate to Severe Atopic Dermatitis (JADE Mono-2)" at ClinicalTrials.gov
  • Clinical trial number NCT03720470 for "Study Evaluating Efficacy and Safety of PF-04965842 and Dupilumab in Adult Subjects With Moderate to Severe Atopic Dermatitis on Background Topical Therapy (JADE Compare)" at ClinicalTrials.gov