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Drugs Mar 2021Tirbanibulin (Klisyri) is a first-in-class Src kinase signaling inhibitor and tubulin polymerisation inhibitor being developed by Athenex in conjunction with global... (Review)
Review
Tirbanibulin (Klisyri) is a first-in-class Src kinase signaling inhibitor and tubulin polymerisation inhibitor being developed by Athenex in conjunction with global partners for the topical treatment of actinic keratosis, and psoriasis. Based on the data from two pivotal phase III trials the drug was recently approved for marketing in the US as a topical treatment for actinic keratosis. This article summarizes the milestones in the development of tirbanibulin leading to this first approval.
Topics: Administration, Topical; Clinical Trials, Phase III as Topic; Humans; Keratosis, Actinic; Polymerization; Protein Kinase Inhibitors; Tubulin; src-Family Kinases
PubMed: 33713299
DOI: 10.1007/s40265-021-01479-0 -
Clinical Drug Investigation Sep 2021We review here the pharmacology, pharmacokinetics, efficacy, dosage and administration, and place in therapy of tirbanibulin for the treatment of actinic keratosis (AK).... (Review)
Review
We review here the pharmacology, pharmacokinetics, efficacy, dosage and administration, and place in therapy of tirbanibulin for the treatment of actinic keratosis (AK). A literature search using PubMed was conducted using the terms tirbanibulin (tirbanibulin) and actinic keratosis from September 2014 to February 2021. All English-language articles evaluating tirbanibulin were analyzed for this review. Tirbanibulin was granted approval for the treatment of AK of the face or scalp as a first-line therapy. It is administered at a dose of 2.5 mg in 250 mg of white or off-white ointment for a 25 cm contiguous treatment surface for 5 consecutive days. Adverse effects include flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. This article discusses the clinical trials that led to the approval of tirbanibulin and comparison with other approved topical ointments indicated for the treatment of AK. In the clinical trials, all participants experienced a decrease in lesion size or saw complete clearance with minimal adverse effects.
Topics: Administration, Topical; Humans; Keratosis, Actinic; Ointments; Protein Kinase Inhibitors; Treatment Outcome
PubMed: 34351607
DOI: 10.1007/s40261-021-01068-9 -
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 -
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 -
American Journal of Health-system... Mar 2021
Topics: Humans; Protein Kinase Inhibitors
PubMed: 33787828
DOI: 10.1093/ajhp/zxab094 -
The New England Journal of Medicine Feb 2021The tubulin polymerization and Src kinase signaling inhibitor tirbanibulin is being investigated as a topical treatment for actinic keratosis, a precursor of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The tubulin polymerization and Src kinase signaling inhibitor tirbanibulin is being investigated as a topical treatment for actinic keratosis, a precursor of squamous-cell carcinoma.
METHODS
In two identically designed double-blind trials, we randomly assigned, in a 1:1 ratio, adults with actinic keratoses on the face or scalp to receive either topical tirbanibulin or vehicle (placebo) ointment. The ointment was applied by the patients to a 25-cm contiguous area containing four to eight lesions once daily for 5 consecutive days. The primary outcome was the percentage of patients with a complete (100%) reduction in the number of lesions in the application area at day 57. The secondary outcome was the percentage of patients with a partial (≥75%) reduction in the number of lesions within the application area at day 57. The incidence of recurrence was evaluated at 1 year. Local reactions were scored with the use of 4-point scale (ranging from 0 [absent] to 3 [severe]).
RESULTS
A total of 702 patients were enrolled in the two trials (351 patients per trial). Complete clearance in trial 1 occurred in 44% of the patients (77 of 175) in the tirbanibulin group and in 5% of those (8 of 176) in the vehicle group (difference, 40 percentage points; 95% confidence interval [CI], 32 to 47; P<0.001); in trial 2, the percentages were 54% (97 of 178 patients) and 13% (22 of 173), respectively (difference, 42 percentage points; 95% CI, 33 to 51; P<0.001). The percentages of patients with partial clearance were significantly higher in the tirbanibulin groups than in the vehicle groups. At 1 year, the estimated percentage of patients with recurrent lesions was 47% among patients who had had a complete response to tirbanibulin. The most common local reactions to tirbanibulin were erythema in 91% of the patients and flaking or scaling in 82%. Adverse events with tirbanibulin were application-site pain in 10% of the patients and pruritus in 9%, all of which resolved.
CONCLUSIONS
In two identically designed trials, tirbanibulin 1% ointment applied once daily for 5 days was superior to vehicle for the treatment of actinic keratosis at 2 months but was associated with transient local reactions and recurrence of lesions at 1 year. Trials comparing tirbanibulin with conventional treatments and that have longer follow-up are needed to determine the effects of tirbanibulin therapy on actinic keratosis. (Funded by Athenex; ClinicalTrials.gov numbers, NCT03285477 and NCT03285490.).
Topics: Acetamides; Administration, Topical; Aged; Double-Blind Method; Enzyme Inhibitors; Face; Female; Humans; Kaplan-Meier Estimate; Keratosis, Actinic; Male; Middle Aged; Morpholines; Ointments; Polymerization; Pyridines; Scalp; Skin; Tubulin
PubMed: 33567191
DOI: 10.1056/NEJMoa2024040 -
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 -
Clinical Pharmacology in Drug... Oct 2021
Review
Topics: Acetamides; Administration, Topical; Enzyme Inhibitors; Humans; Keratosis, Actinic; Morpholines; Pyridines; Treatment Outcome
PubMed: 34612001
DOI: 10.1002/cpdd.1024