|Drug class||Microtubule inhibitor|
|Main uses||Actinic keratosis|
|Side effects||Local skin reactions, itchiness, skin pain|
|Chemical and physical data|
|Molar mass||431.536 g·mol−1|
|3D model (JSmol)|
Tirbanibulin, sold under the brand name Klisyri, is a medication used to treat actinic keratosis of the face or scalp. It is used for five days in mild disease with reassessment after 8 weeks. It is applied to the skin.
Common side effects include local skin reactions, itchiness, and skin pain. Other side effects may include skin ulcers. There are concerns of harm when used during pregnancy in other animals; however, safety is human pregnancy is unclear. It is a microtubule inhibitor.
Tirbanibulin was approved for medical use in the United States in 2020 and Europe in 2021. In the United Kingdom a course of treatment costs the NHS about £60 as of 2022. This amount in the United States costs about 1,000 USD.
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.
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.
Mechanism of Action
It functions as a mitotic inhibitor by inhibiting tubulin polymerization and Src kinase signaling can be potentially effective in deferring the development of AKs to squamous cell carcinoma in situ.
Tirbanibulin, chemically known as N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl) pyridine-2-yl) acetamide, is a microtubule and non–ATP-competitive inhibitor. The drug in various ways mimics the mechanisms of chemotherapy 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.
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. The trials were conducted at 62 sites in the United States. 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. Neither the participants nor the health care providers knew which treatment was being given until after the trial was completed. 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). The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.
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. The applicant for this medicinal product is Almirall, S.A. Tirbanibulin was approved for medical use in the European Union in July 2021.
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- 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