Tirbanibulin

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Tirbanibulin
Clinical data
Trade namesKlisyri, Onakta
Other namesKX2-391
AHFS/Drugs.comMonograph
License data
Pregnancy
category
Microtubule inhibitor
ATC code
Legal status
Legal status
Identifiers
  • N-benzyl-2-[5-[4-(2-morpholin-4-ylethoxy)phenyl]pyridin-2-yl]acetamide
JSmol)
  • O=C(Cc1ccc(-c2ccc(OCCN3CCOCC3)cc2)cn1)NCc1ccccc1
  • 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 for the treatment of actinic keratosis (AKs) on the face or scalp.[4][5][6] It functions as a mitotic inhibitor by inhibiting tubulin polymerization and Src kinase signaling.[7] It is potentially effective in deferring the development of AKs to squamous cell carcinoma in situ.[8]

The most common side effects include local skin reactions, application site pruritus, and application site pain.[4][5]

Tirbanibulin was approved for medical use in the United States in December 2020,[5][9][10] and in the European Union in July 2021.[6] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[11]

Medical uses

Tirbanibulin is indicated for the topical treatment of actinic keratosis of the face or scalp.[4][5][6]

Mechanism of Action

Tirbanibulin, chemically known as N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl) pyridine-2-yl) acetamide, is a microtubule and non–ATP-competitive inhibitor.[8] The drug in various ways mimics the mechanisms of chemotherapy[12] 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.[8]

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.[12]

Extensive research has not been conducted on the risks of tirbanibulin usage by specific human populations (i.e., pregnant populations). Significant differences have not been observed in the safety or effectiveness of tirbanibulin between geriatric or pediatric populations.[13]

History

The US 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.[5] The trials were conducted at 62 sites in the United States.[5] 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.[5] Neither the participants nor the health care providers knew which treatment was being given until after the trial was completed.[5] 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).[5]

Society and culture

Legal status

In 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.[14] The applicant for this medicinal product is Almirall, S.A. Tirbanibulin was approved for medical use in the European Union in July 2021.[6][15]

References

  1. ^ a b "Onakta APMDS". Therapeutic Goods Administration (TGA). 6 March 2024. Retrieved 7 March 2024.
  2. ^ "Summary Basis of Decision for Onakta". Health Canada. 20 July 2023. Archived from the original on 10 March 2024. Retrieved 4 October 2023.
  3. ^ "Details for: Onakta". Health Canada. 12 May 2023. Archived from the original on 10 March 2024. Retrieved 4 October 2023.
  4. ^ a b c d "Klisyri- tirbanibulin ointment". DailyMed. Archived from the original on 11 January 2021. Retrieved 8 January 2021.
  5. ^ a b c d e f g h i j "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.
  6. ^ a b c d e "Klisyri EPAR". European Medicines Agency (EMA). 20 April 2021. 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.
  7. PMID 31628188
    .
  8. ^
    PMID 34301153
    .
  9. ^ "Drug Approval Package: Klisyri". U.S. Food and Drug Administration (FDA). 28 December 2020. Archived from the original on 12 January 2021. Retrieved 8 January 2021.
  10. ^ "Athenex Announces FDA Approval of Klisyri (Tirbanibulin) for the Treatment of Actinic Keratosis on the Face or Scalp" (Press release). Athenex Inc. 15 December 2020. Archived from the original on 19 December 2020. Retrieved 15 December 2020 – via GlobeNewswire.
  11. ^ "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.
  12. ^
    PMID 34783508. Archived
    from the original on 1 November 2022. Retrieved 11 May 2022.
  13. PMID 33787828
    .
  14. ^ "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.
  15. ^ "Klisyri Product information". Union Register of medicinal products. Archived from the original on 5 March 2023. Retrieved 3 March 2023.

External links

  • 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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