By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
The FDA has approved a first-in-class topical drug for the treatment of actinic keratosis (AK). Tirbanibulin is a microtubule inhibitor with antiproliferative activity. It is distributed as Klisyri.
Tirbanibulin is indicated for the topical treatment of AK on the face and scalp.1
Apply a single-dose packet to the treatment field (up to 25 cm2) on face or scalp once daily for five consecutive days.1 Tirbanibulin 1% ointment is available as a single-dose packet.
Tirbanibulin offers a new mechanism of action. Its short treatment regimen (five days) may improve adherence. Local reactions were mostly mild and transient.2
The most frequently reported adverse reactions compared to the vehicle were moderate erythema (63% vs. 6%) and moderate flaking/scaling (47% vs. 9%).1 AK lesions tend to recur at 12 months.1
The efficacy of tirbanibulin was established in two double-blind, vehicle-controlled trials in adult subjects with AK on the face or scalp.1 Subjects (mainly white men with Fitzpatrick skin types II and III) exhibited four to eight clinically typical, visible, and discrete AK lesions on the face or scalp with a contiguous area of 25 cm2. They were randomized to tirbanibulin (n = 175 in study 1 and n = 178 in study 2) or vehicle (n = 176 and 173, respectively). Subjects received five consecutive days of treatment. The primary endpoint was the proportion of subjects with complete (100%) clearance of AK. The secondary endpoint was partial clearance (≥ 75%). Subjects with complete clearance returned for assessment of recurrence every three months for 12 months after day 57.
Complete clearance rates were 44% (study 1) and 54% (study 2) at day 57 vs. 5% and 13% for vehicle, respectively, showing treatment differences of 40% and 42%. Tirbanibulin was more effective on face lesions compared to scalp lesions (50% and 54% vs. 30% and 41%, respectively). The recurrence rate at 12 months was 73%.1 Partial clearance rates (vs. placebo) were 68% vs. 16% for study 1 and 76% vs. 20% for study 2. Cost information is not available yet.
AK is a common skin lesion in older, fair-skinned individuals resulting from cumulative sun exposure.2 A portion may progress to invasive squamous cell carcinoma.3-5 The treatment goal is to eradicate both clinical and subclinical AK lesions and maintain a disease-free interval as long as possible.4 Spontaneous resolution is reported to occur in 15% to 63% of lesions after one year.5 Treatment/removal modalities include nondrug (e.g., cryotherapy, curettage,) that are lesion-directed or topical treatment (e.g., fluorouracil, imiquimod, ingenol mebutate, diclofenac gel, or photodynamic therapy) for field-directed treatment of multiple lesions.6,7 For topical options, fluorouracil and imiquimod represent 80% of the market, with ingenol mebutate and diclofenac with 10% each.4 The authors of a randomized trial compared four treatments in 624 subjects with AK (five or more lesions on the head, approximately 50% of the face) with one continuous area of 25 cm2 to 100 cm2.8 Fluorouracil was applied twice daily for four weeks. Imiquimod was applied once daily three days per week for four weeks. Ingenol mebutate was applied once daily for three consecutive days. Some subjects also underwent methyl aminolevulinate photodynamic therapy (PDT). All patients could receive a maximum of two courses of assigned treatment. Treatment success was assessed at 12 months after last treatment. The cumulative probabilities of treatment success were 75% for fluorouracil, 54% for imiquimod, 38% for PDT, and 29% for ingenol mebutate. The lower rate for imiquimod may be because a shorter treatment duration is recommended. Fluorouracil was not associated with higher frequency of adverse events than other treatments. Diclofenac, not included in the study, requires treatment for two to three months.6 Fluorouracil may be less preferable for the face because of skin reaction (e.g., local inflammation).6 Tirbanibulin may be an option for the face because of its mild to moderate local reaction and short treatment duration. The potential downside is a high recurrence rate.
- Almirall, LLC. Klisyri prescribing information. December 2020.
- Kempers S, DuBois J, Forman S, et al. Tirbanibulin ointment 1% as a novel treatment for actinic keratosis: Phase 1 and 2 results. J Drugs Dermatol 2020;19:1093-1100.
- Rosen T, Lebwohl MG. Prevalence and awareness of actinic keratosis: barriers and opportunities. J Am Acad Dermatol 2013;68:S2-S9.
- Cramer P, Stockfleth E. Actinic keratosis: Where do we stand and where is the future going to take us? Exp Opin Emerg Drugs 2020;25:49-58.
- Center for Drug Research and Evaluation. NDA 213189 Multidisciplinary review and evaluation. Oct. 12, 2018.
- American Academy of Dermatology Association. Actinic keratosis: Diagnosis and treatment.
- Goldenberg G. Treatment considerations in actinic keratosis. J Eur Acad Dermatol Venereol 2017;31:12-16.
- Jansen MHE, Kessels JPHM, Nelemans PJ, et al. Randomized trial of four treatment approaches for actinic keratosis. N Engl J Med 2019;380:935-946.