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Trade names | Klisyri, Onakta |
Other names | KX2-391 |
AHFS/Drugs.com | Monograph |
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Routes of administration | Topical |
Drug class | Microtubule inhibitor |
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ECHA InfoCard | 100.305.161 |
Chemical and physical data | |
Formula | C26H29N3O3 |
Molar mass | 431.536 g·mol−1 |
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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]
Tirbanibulin is indicated for the topical treatment of actinic keratosis of the face or scalp. [4] [5] [6]
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]
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]
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]
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]
Actinic keratosis (AK), sometimes called solar keratosis or senile keratosis, is a pre-cancerous area of thick, scaly, or crusty skin. Actinic keratosis is a disorder of epidermal keratinocytes that is induced by ultraviolet (UV) light exposure. These growths are more common in fair-skinned people and those who are frequently in the sun. They are believed to form when skin gets damaged by UV radiation from the sun or indoor tanning beds, usually over the course of decades. Given their pre-cancerous nature, if left untreated, they may turn into a type of skin cancer called squamous cell carcinoma. Untreated lesions have up to a 20% risk of progression to squamous cell carcinoma, so treatment by a dermatologist is recommended.
Imiquimod, sold under the brand name Aldara among others, is a medication that acts as an immune response modifier that is used to treat genital warts, superficial basal cell carcinoma, and actinic keratosis.
Lonafarnib, sold under the brand name Zokinvy, is a medication used to reduce the risk of death due to Hutchinson-Gilford progeria syndrome and for the treatment of certain processing-deficient progeroid laminopathies in people one year of age and older.
Rucaparib, sold under the brand name Rubraca, is a PARP inhibitor used as an anti-cancer agent. Rucaparib is a first-in-class pharmaceutical drug targeting the DNA repair enzyme poly-ADP ribose polymerase-1 (PARP-1). It is taken by mouth.
Ingenol mebutate, sold under the brand name Picato, is a substance that is found in the sap of the plant Euphorbia peplus, commonly known as petty spurge, and is an inducer of cell death. This compound was isolated first from this plant in 2000. A gel formulation of the drug has been approved by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) for the topical treatment of actinic keratosis. Two different strengths of the gel have been approved for use on either the face and scalp (0.015%) or the trunk and extremities (0.05%), respectively. In 2020 the drug was withdrawn from the market in the EU.
Baricitinib, sold under the brand name Olumiant among others, is an immunomodulatory medication used for the treatment of rheumatoid arthritis, alopecia areata, and COVID-19. It acts as an inhibitor of janus kinase (JAK), blocking the subtypes JAK1 and JAK2.
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Capmatinib, sold under the brand name Tabrecta, is an anticancer medication used for the treatment of metastatic non-small cell lung cancer whose tumors have a mutation that leads to the exon 14 skipping of the MET gene, which codes for the membrane receptor HGFR.
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Ivosidenib, sold under the brand name Tibsovo, is an anti-cancer medication for the treatment of acute myeloid leukemia (AML) and cholangiocarcinoma. It is a small molecule inhibitor of isocitrate dehydrogenase-1 (IDH1), which is mutated in several forms of cancer. Ivosidenib is an isocitrate dehydrogenase-1 inhibitor that works by decreasing abnormal production of the oncometabolite 2-hydroxyglutarate (2-HG), leading to differentiation of malignant cells.
Sotorasib, sold under the brand names Lumakras and Lumykras, is an anti-cancer medication used to treat non-small-cell lung cancer. It targets a specific mutation, G12C, in the protein K-Ras encoded by gene KRAS which is responsible for various forms of cancer. Sotorasib is an inhibitor of the RAS GTPase family.
Avapritinib, sold under the brand name Ayvakit among others, is a medication used for the treatment of advanced systemic mastocytosis and for the treatment of tumors due to one specific rare mutation: it is specifically intended for adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) that harbor a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation. Avapritinib is a kinase inhibitor.
Pemigatinib, sold under the brand name Pemazyre, is an anti-cancer medication used for the treatment of bile duct cancer (cholangiocarcinoma). Pemigatinib works by blocking FGFR2 in tumor cells to prevent them from growing and spreading.
Pralsetinib, sold under the brand name Gavreto, is a medication approved for RET mutation-positive medullary thyroid cancer (MTC) and RET fusion-positive differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) therapy. Pralsetinib is a tyrosine kinase inhibitor. It is taken by mouth.
Adagrasib, sold under the brand name Krazati, is an anticancer medication used to treat non-small cell lung cancer. Adagrasib is an inhibitor of the RAS GTPase family. It is taken by mouth. It is being developed by Mirati Therapeutics.
Avacopan, sold under the brand name Tavneos, is a medication used to treat anti-neutrophil cytoplasmic autoantibody-associated vasculitis. Avacopan is a complement 5a receptor antagonist and a cytochrome P450 3A4 inhibitor.
Asciminib, sold under the brand name Scemblix, is a medication used to treat Philadelphia chromosome-positive chronic myeloid leukemia. Asciminib is a protein kinase inhibitor.