Tirbanibulin for Actinic Keratosis: Insights into the Mechanism of Action.

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.

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© 2022 Schlesinger et al.

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Brian Berman has received grants or research funding from Biofrontera, LEO Pharma, and Sirnaomics. He is a consultant to Aiviva, Almirall, Biofrontera, Castle Biosciences, Inc., LEO Pharma, Mediwound, PHD Biosciences, Sirnaomics, and Sun Pharma. He has attended speakers’ bureaus for Almirall, and Sun Pharma, and served on advisory boards for Almirall, Biofrontera, Castle Biosciences, Inc., LEO Pharma, and Sun Pharma. Todd Schlesinger has received grants or research funding from AbbVie, Aclaris Therapeutics, Inc., Akros Pharma, Inc., Allergan, AOBiome Therapeutics, Arcutis Biotherapeutics, Astellas Pharma US, Inc., Bioderma Laboratories, Biofrontera, BioPharmX, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle Biosciences, Inc., Celgene, ChemoCentryx, Coherus BioSciences, Corrona, Dermavant, Dermira, Inc., DT Collagen & DT Pharmacy, Eli Lilly & Co., Almirall, Galderma, Genentech, Inc., Janssen/Centocor Ortho Biotech, Inc., Kinex, Kiniksa Pharmaceuticals, LEO Pharma, Merz Pharma, Novartis, Pfizer, Inc., Regeneron Pharmaceuticals, Sanofi Genzyme, SiSaf, Ltd., Tetraderm Group, LLC, and Trevi Therapeutics. He is a consultant to AbbVie, Aclaris Therapeutics, Inc., Allergan, Almirall, Biofrontera, Bristol-Myers Squibb, Castle Biosciences, Inc., Eli Lilly & Co., EPI Health, Evolus, Foundation for Research and Education in Dermatology, Galderma, LEO Pharma, MED Learning Group CME Program, Merz Pharma, MJH Associates ONCLive SCC Filming, Novartis, Ortho Dermatologics, Pfizer, Inc., Prolacta Bioscience, Regeneron Pharmaceuticals, SiSaf, Ltd., Sun Pharma, Suneva Medical, Inc., and UCB Pharma. He has attended speakers’ bureaus for Aclaris Therapeutics, Inc., Almirall, Dermira, Inc., DUSA Pharmaceuticals, EPI Health, Regeneron Pharmaceuticals, Sanofi-Aventis, Sanofi Genzyme, Sun Pharma, and Suneva Medical, Inc.; and served on advisory boards for Allergan, Almirall, Bioderma Laboratories, Biofrontera, Celgene, Greenway Therapeutix, Remedly, and Suneva Medical, Inc. He is also co-chair committee and/or performance measurement, corporate relations committee member for American Academy of Dermatology Actinic Keratosis Guideline and Actinic Keratosis Performance Measurement Work Group. Eggert Stockfleth has received grants or research funding from Almirall, Pierre Fabre, Aresus and Dr Pfleger. Ayman Grada is the Former Head of R&D and Medical Affairs at Almirall (US). The authors report no other conflicts of interest in this work.