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The Annals of Pharmacotherapy Apr 2022Actinic keratoses (AKs) are cutaneous lesions that arise in sun-damaged skin. AKs may transform into squamous cell carcinoma in situ. Tirbanibulin 1% ointment is a new... (Review)
Review
OBJECTIVE
Actinic keratoses (AKs) are cutaneous lesions that arise in sun-damaged skin. AKs may transform into squamous cell carcinoma in situ. Tirbanibulin 1% ointment is a new topical treatment for AKs, recently approved by the Food and Drug Administration.
DATA SOURCES
The PubMed database was searched for articles published from 1960 to March 31, 2021, using the keywords and .
DATA EXTRACTION
Phase 2 and phase 3 clinical trials were reviewed.
DATA SYNTHESIS
In phase 2 clinical trials, 43% of patients treated with tirbanibulin experienced complete clearance by day 57 (43% [95% CI = 32, 54]). Across two phase 3 clinical trials (pooled data), complete (100%) clearance occurred in 49% of patients in tirbanibulin groups and in only 9% of the vehicle groups (difference, 41% points; 95% CI = 35 to 47; < 0.001). Although no comparative studies are available, tirbanibulin is applied for a shorter duration (5 days) compared with diclofenac 3% gel, fluorouracil 5% cream, and imiquimod 3.75% cream. Adverse events were mild and included pruritus, application site pain, and local skin reactions. Systemic adverse events such as necrosis and angioedema, observed with other AK treatments such as fluorouracil and imiquimod, were not observed with tirbanibulin, thus giving tirbanibulin a favorable safety profile.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Tirbanibulin effectively reduces AK burden and recurrence and has a favorable safety profile with mild adverse events. In comparison, imiquimod, 5-flourouracil, and diclofenac can result in necrosis, angioedema, and arthralgias.
CONCLUSION
With a favorable safety profile and short regimen, tirbanibulin is an efficacious treatment for clinicians to utilize in their treatment toolbox when treating AKs on the face and scalp.
Topics: Acetamides; Humans; Keratosis, Actinic; Morpholines; Ointments; Pyridines; Treatment Outcome; United States
PubMed: 34301153
DOI: 10.1177/10600280211031329 -
Clinical, Cosmetic and Investigational... 2022Actinic keratosis (AK) is a common pre-neoplastic skin lesion constituted by uncontrolled proliferation of atypical keratinocytes that may evolve to squamous cell... (Review)
Review
Actinic keratosis (AK) is a common pre-neoplastic skin lesion constituted by uncontrolled proliferation of atypical keratinocytes that may evolve to squamous cell carcinoma. With global prevalence increasing, AK is expected to be the most common carcinoma of the skin. Tirbanibulin is a reversible tubulin polymerization inhibitor with potent anti-proliferative and anti-tumoral effects. In-vivo and in-vitro studies have shown that tirbanibulin significantly inhibits cell proliferation, tumor growth and downregulates Src signaling with no overt toxicity. Early phase and Phase III trials have shown high lesion clearance, compliance, and few side effects of once daily tirbanibulin treatment. This review discusses tirbanibulin anti-cancer activity, focusing on tubulin polymerization and Src signaling inhibitory effects, highlighting relevant literature and novel preclinical results from the ATNXUS-KX01-001 study. Furthermore, we address the relevant findings obtained in recent clinical trials to evaluate the safety, efficacy, pharmacokinetics, clearance efficacy, and side effects of the 1% tirbanibulin ointment applied once daily. In summary, we highlight preclinical and clinical evidence on the use of tirbanibulin as an effective and safe treatment option for AK.
PubMed: 36415541
DOI: 10.2147/CCID.S374122 -
Skin Therapy Letter Jul 2022Actinic keratosis (AK) is a common precancerous condition found on chronically sun-damaged skin, particularly on the face, scalp, arms, and legs. Early and effective... (Review)
Review
Actinic keratosis (AK) is a common precancerous condition found on chronically sun-damaged skin, particularly on the face, scalp, arms, and legs. Early and effective treatment of AKs is important to prevent progression to squamous cell carcinoma. Many topical treatments for AKs are often limited because of poor tolerability, prolonged treatment duration, and reduced adherence. Tirbanibulin 1% ointment, a new topical field therapy for AKs, reduces these issues. It requires a consecutive 5-day application period and is effective, demonstrating complete (100%) clearance of AK lesions in 49% of patients, partial (>75%) clearance in 72%, and a median reduction in lesion count of 87.5% while exhibiting a favorable safety profile, mild adverse events, improved tolerability, and long-term results.
Topics: Acetamides; Administration, Topical; Humans; Keratosis, Actinic; Morpholines; Pyridines; Scalp; Treatment Outcome
PubMed: 35857917
DOI: No ID Found -
Actas Dermo-sifiliograficas Jan 2022Actinic keratosis (AK) is a skin condition characterized by the proliferation of mutated keratinocytes that can develop into squamous cell carcinoma. Available... (Review)
Review
Actinic keratosis (AK) is a skin condition characterized by the proliferation of mutated keratinocytes that can develop into squamous cell carcinoma. Available therapies, although effective, are associated with a high frequency of severe local skin reactions. Tirbanibulin, one of the treatments for AK currently in development, is a new synthetic chemical entity with anti-proliferative and anti-tumor effects, both in vitro and in vivo, with proved efficacy in the treatment of AK, which has been recently demonstrated in two phase III clinical trials. In the present review, the tirbanibulin mechanism of action, based on the relevant literature and the results of several unpublished preclinical studies, is shown. In addition, the current scenario regarding the available treatments and how the novel tirbanibulin mechanism of action fits into the treatment of AK is raised.
PubMed: 35249711
DOI: 10.1016/j.ad.2021.07.006 -
The Journal of Clinical and Aesthetic... Oct 2022Actinic keratosis (AK) is a chronic disease resulting from deleterious effects of long-term, cumulative, epidermal exposure to ultraviolet (UV) light. UV-induced...
Actinic keratosis (AK) is a chronic disease resulting from deleterious effects of long-term, cumulative, epidermal exposure to ultraviolet (UV) light. UV-induced mutations in p53, ras, and p16 genes lead to the emergence of abnormal epidermal actinic keratosis (AKs) cells, which proliferate while avoiding apoptosis and may lead to invasive squamous cell carcinoma. There are both lesion-targeted and field-directed topical treatments. This review is of new and emerging information on tirbanibulin and tirbanibulin 1% ointment, which is approved for topical field treatment of actinic keratosis on the face and scalp. Potent antiproliferative and proapoptotic activities result from tirbanibulin's inhibition tubulin polymerization and disruption of microtubule formation and Src kinase signaling. Tirbanibulin 1% ointment is an effective treatment of facial and scalp AK after five consecutive once-daily applications, as measured by complete and partial clearance and percent reduction in the number of lesions. Localized skin reactions are usually mild to moderate, resolving within a month. The short and well-tolerated course of therapy results in very high patient adherence to the treatment regimen.
PubMed: 36408375
DOI: No ID Found -
PharmacoEconomics - Open May 2023Tirbanibulin 1% ointment is a new treatment for actinic keratosis (AK) on the face or scalp. A health economic model was developed as part of a submission to the...
BACKGROUND
Tirbanibulin 1% ointment is a new treatment for actinic keratosis (AK) on the face or scalp. A health economic model was developed as part of a submission to the Scottish Medicines Consortium to evaluate the cost-effectiveness of tirbanibulin compared to the most frequently prescribed treatments.
METHODS
A decision tree approach was used to calculate the costs and benefits of different treatment strategies for AK on the face or scalp over a one-year time horizon. Data on the relative efficacy of treatments, which were based on the probability of complete clearance of AK, were obtained from a network meta-analysis. Sensitivity and scenario analyses were performed to determine the robustness of the model results.
RESULTS
Tirbanibulin is estimated to be cost saving versus diclofenac sodium 3%, imiquimod 5% and fluorouracil 5%. Tirbanibulin remains cost saving when inputs are varied in sensitivity and scenario analyses. While the complete clearance rates are deemed similar across comparators, tirbanibulin is associated with a lower rate of severe local skin reactions, and a shorter treatment duration, which may improve treatment adherence.
CONCLUSIONS
Tirbanibulin is a cost saving intervention for the treatment of AK from the perspective of the Scottish Healthcare System.
PubMed: 37012513
DOI: 10.1007/s41669-023-00410-5 -
RSC Advances Nov 2023Tirbanibulin, an FDA-approved microtubule-targeting agent (MTA) introduced in 2020, represents a pioneering treatment for precancerous actinic keratosis. Despite its...
Tirbanibulin, an FDA-approved microtubule-targeting agent (MTA) introduced in 2020, represents a pioneering treatment for precancerous actinic keratosis. Despite its failure to gain approval as an anticancer agent due to insufficient efficacy, there remains potential value in extending its application into malignancy treatment through tirbanibulin-based derivatives. Tirbanibulin possesses a distinctive dual mechanism of action involving microtubule and Src inhibition, distinguishing it from other MTAs. In spite of its unique profile, exploration of tirbanibulin's structure-activity relationship (SAR) and the development of its derivatives are significantly limited in the current literature. This study addresses this gap by synthesizing various tirbanibulin derivatives and exploring their SAR through modifications in the core amide motif and the eastern benzylamine part. Our results underscore the critical role of the pyridinyl acetamide core structure for optimal cellular potency, with favorable tolerance observed for modifications at the position of the benzylamine moiety. Particularly noteworthy is the analogue modified with -fluorine benzylamine, which exhibited favorable PK profiles. These findings provide crucial insights into the potential advancement of tirbanibulin-based compounds as promising anticancer agents.
PubMed: 38077981
DOI: 10.1039/d3ra06790d -
Journal of Clinical Medicine Jul 2023Actinic keratosis (AK) is a cutaneous lesion resulting from the proliferation of atypical epidermal keratinocytes caused by long-term exposure to ultraviolet radiation....
BACKGROUND
Actinic keratosis (AK) is a cutaneous lesion resulting from the proliferation of atypical epidermal keratinocytes caused by long-term exposure to ultraviolet radiation. AK may progress to cutaneous squamous cell carcinoma (cSCC) and therefore is often treated with topical agents such as 5-fluorouracil, diclofenac, imiquimod, and photodynamic therapy. Tirbanibulin has been approved based on two phase III trials in the USA. However, real-world evidence for tirbanibulin is absent.
METHODS
This was a single-centre study of adult patients with clinically typical, visible AK on the face or scalp treated with tirbanibulin 1% ointment. Treatment was administered as per label once daily for 5 consecutive days on the same lesions or field. Treatment outcomes were assessed 4 weeks after treatment, with additional optional assessments conducted at later time points. Efficacy was measured using the actinic keratosis area and severity index (AKASI) and digital dermoscopy.
RESULTS
A total of 33 patients were treated of whom 30 were analysed. The median AKASI score was 5.6 (1.4-11) pre-treatment and 1.2 (0-7.4) post-treatment ( < 0.0001). Complete clearance as defined by AKASI scores less than 1 was achieved in 47% ( = 14) and 57% ( = 13) at the first and second follow-up, respectively. All local reactions resolved spontaneously and without sequelae. The most common local reactions were erythema (80%, = 26) and flaking or scaling (43%, = 13).
CONCLUSIONS
Tirbanibulin 1% ointment significantly and rapidly reduced the AKASI score in a real-world setting. The complete clearance rates were in line with those observed in the two pivotal trials.
PubMed: 37510952
DOI: 10.3390/jcm12144837 -
JID Innovations : Skin Science From... Mar 2023Tirbanibulin 1% ointment is approved for the topical treatment of actinic keratosis, applied once daily for 5 days. Three phase 1 randomized, single-center, controlled,...
Tirbanibulin 1% ointment is approved for the topical treatment of actinic keratosis, applied once daily for 5 days. Three phase 1 randomized, single-center, controlled, within-subject comparison studies were conducted to evaluate the sensitization (KX01-AK-006), phototoxic (KX01-AK-008), and photoallergic (KX01-AK-009) potential of tirbanibulin 1% ointment in healthy adults. In KX01-AK-006 and KX01-AK-009, subjects received repeated applications of tirbanibulin or vehicle for induction (followed by irradiation in KX01-AK-009) and an additional application for the challenge on naïve sites. In KX01-AK-008, subjects received single applications, followed by irradiation. Sensitization was defined as a reaction scoring 3 at naïve sites, recurring at rechallenge. Photoallergy was assessed based on the dermal response of erythema + edema at naïve sites. Phototoxicity was assessed based on the average dermal response score (days 3‒4). Adverse events were collected. In KX01-AK-006, none of the 229 subjects scored 3 at naïve sites. In KX01-AK-008, none of the 31 subjects developed edema, not meeting the criteria for phototoxicity. In KX01-AK-009, none of the 59 subjects showed reactions compatible with photoallergy. Mild-to-moderate contact irritations were reported. The evidence provided by these phase 1 studies showed that tirbanibulin 1% ointment lacks sensitization and phototoxic or photoallergic potential, and supports the safety of its topical application.
PubMed: 36699198
DOI: 10.1016/j.xjidi.2022.100170