Tirbanibulin

Tirbanibulin
Names
Trade namesKlisyri
Other namesKX2-391
IUPAC name
  • N-benzyl-2-[5-[4-(2-morpholin-4-ylethoxy)phenyl]pyridin-2-yl]acetamide
Clinical data
Drug classMicrotubule inhibitor
Main usesActinic keratosis[1][2]
Side effectsLocal skin reactions, itchiness, skin pain[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Routes of
use		Topical
External links
AHFS/Drugs.comMonograph
Legal
License data
Legal status
Chemical and physical data
FormulaC26H29N3O3
Molar mass431.536 g·mol−1
3D model (JSmol)
SMILES
  • O=C(Cc1ccc(-c2ccc(OCCN3CCOCC3)cc2)cn1)NCc1ccccc1
InChI
  • InChI=1S/C26H29N3O3/c30-26(28-19-21-4-2-1-3-5-21)18-24-9-6-23(20-27-24)22-7-10-25(11-8-22)32-17-14-29-12-15-31-16-13-29/h1-11,20H,12-19H2,(H,28,30)
  • Key:HUNGUWOZPQBXGX-UHFFFAOYSA-N

Tirbanibulin, sold under the brand name Klisyri, is a medication used to treat actinic keratosis of the face or scalp.[1][2] It is used for five days in mild disease with reassessment after 8 weeks.[2][1] It is applied to the skin.[1]

Common side effects include local skin reactions, itchiness, and skin pain.[1] Other side effects may include skin ulcers.[1] There are concerns of harm when used during pregnancy in other animals; however, safety is human pregnancy is unclear.[1] It is a microtubule inhibitor.[1]

Tirbanibulin was approved for medical use in the United States in 2020 and Europe in 2021.[1][2] In the United Kingdom a course of treatment costs the NHS about £60 as of 2022.[4] This amount in the United States costs about 1,000 USD.[5]

Medical uses

Tirbanibulin is indicated for the topical treatment of actinic keratosis of the face or scalp.[1][3][2] It clears the disease in about 40 to 50% of people as compared to placebo at 5 to 10%.[2]

Dosage

It is applied to the skin of the affected area once a day for five days.[1] It comes as a 1% ointment.[1]

Side effects

In several studies tirbanibulin has been observed to induce skin reactions at the site of application, ranging from mild to severe erythema, flaking, ulceration, and pain.[6]

As of now, there has been no extensive research conducted on the risks of tirbanibulin usage by specific human populations (i.e., pregnant populations). There also has been no significant differences observed in safety or effectiveness of the drug between geriatric or pediatric populations.[7]

Mechanism of Action

It functions as a mitotic inhibitor by inhibiting tubulin polymerization and Src kinase signaling[8] can be potentially effective in deferring the development of AKs to squamous cell carcinoma in situ.[9]

Tirbanibulin, chemically known as N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl) pyridine-2-yl) acetamide, is a microtubule and non–ATP-competitive inhibitor.[9] The drug in various ways mimics the mechanisms of chemotherapy[6] by suspending the protooncogenic Src tyrosine kinase signaling pathway. Notably, it promotes G2/M arrest during cell cycle, upregulates p53, and triggers apoptosis via caspase-3 stimulation and poly (ADP-ribose) polymerase cleavage.[9]

History

The U.S. Food and Drug Administration (FDA) approved tirbanibulin based on evidence from two clinical trials (Trial 1/ NCT03285477 and Trial 2/NCT03285490) of 702 adults with actinic keratosis on the face or scalp.[3] The trials were conducted at 62 sites in the United States.[3] Participants received once daily treatment with either tirbanibulin or inactive control ointment for 5 consecutive days to the single predetermined area where they had actinic keratosis.[3] Neither the participants nor the health care providers knew which treatment was being given until after the trial was completed.[3] The benefit of tirbanibulin in comparison to control was assessed after 57 days by comparing the percentage of participants who did not have any actinic keratosis on the treatment area (100% clearance).[3] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[10]

Society and culture

On 20 May 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 tirbanibulin, intended for the treatment of actinic keratosis.[11] The applicant for this medicinal product is Almirall, S.A. Tirbanibulin was approved for medical use in the European Union in July 2021.[2]

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 "Klisyri- tirbanibulin ointment". DailyMed. Archived from the original on 11 January 2021. Retrieved 8 January 2021.
  2. 1 2 3 4 5 6 7 8 "Klisyri EPAR". European Medicines Agency (EMA). Archived from the original on 23 July 2021. Retrieved 22 July 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  3. 1 2 3 4 5 6 7 "Drug Trials Snapshot: Klisyri". U.S. Food and Drug Administration (FDA). 14 December 2020. Archived from the original on 8 January 2021. Retrieved 8 January 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  4. ↑ "Tirbanibulin". SPS - Specialist Pharmacy Service. 29 November 2018. Archived from the original on 5 March 2022. Retrieved 3 November 2022.
  5. ↑ "Klisyri". Retrieved 3 November 2022.
  6. 1 2 Geer, Kamini (1 November 2021). "Tirbanibulin (Klisyri) for the Treatment of Actinic Keratosis". American Family Physician. 104 (5): 519–521. PMID 34783508. Archived from the original on 1 November 2022. Retrieved 8 August 2022.
  7. ↑ "Tirbanibulin". American Journal of Health-System Pharmacy. 78 (8): 656–657. 31 March 2021. doi:10.1093/ajhp/zxab094. ISSN 1079-2082. PMID 33787828. Archived from the original on 1 November 2022. Retrieved 8 August 2022.
  8. ↑ Niu L, Yang J, Yan W, Yu Y, Zheng Y, Ye H, et al. (November 2019). "Reversible binding of the anticancer drug KXO1 (tirbanibulin) to the colchicine-binding site of β-tubulin explains KXO1's low clinical toxicity". The Journal of Biological Chemistry. 294 (48): 18099–18108. doi:10.1074/jbc.RA119.010732. PMC 6885616. PMID 31628188.
  9. 1 2 3 Dao, Diem-Phuong D.; Sahni, Vikram Nath; Sahni, Dev Ram; Balogh, Esther A.; Grada, Ayman; Feldman, Steven R. (April 2022). "1% Tirbanibulin Ointment for the Treatment of Actinic Keratoses". Annals of Pharmacotherapy. 56 (4): 494–500. doi:10.1177/10600280211031329. ISSN 1060-0280. PMC 8899810. PMID 34301153.
  10. ↑ "New Drug Therapy Approvals 2020". U.S. Food and Drug Administration (FDA). 31 December 2020. Archived from the original on 18 January 2021. Retrieved 17 January 2021.
  11. ↑ "Klisyri: Pending EC decision". European Medicines Agency. 21 May 2021. Archived from the original on 23 May 2021. Retrieved 23 May 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
External sites:
Identifiers:
  • Clinical trial number NCT03285477 for "A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on AK on Face or Scalp (AK003)" at ClinicalTrials.gov
  • Clinical trial number NCT03285490 for "A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on AK on Face or Scalp (AK004)" at ClinicalTrials.gov
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