Tirbanibulin 1% Ointment Clears Actinic Keratoses Lesions, But at What Expense?

The results of 2 Phase 3 trials evaluating the efficacy and safety of topical tirbanibulin for treating patients with actinic keratosis are reviewed.

Once-daily tirbanibulin 1% ointment cleared actinic keratosis lesions better than vehicle during 2 months, but treatment with tirbanibulin was associated with more transient local reactions and recurrent lesions at 1-year follow up. This is according to data from 2 phase 3 studies published in the New England Journal of Medicine.

Patients with actinic keratosis on the face or scalp were randomly assigned to topical tirbanibulin 1% ointment (n=175 in trial 1; n=178 in trial 2) or a vehicle placebo ointment (n=176 in trial 1; n=173 in trial 2) in 2 identically designed, double-blind trials. The ointments were applied once daily for 5 days on areas that contained 4 to 8 lesions. The patients who experienced complete reduction in lesion number at 57 days comprised the primary outcome.

In addition, the investigators recorded the percentage of patients who experienced a partial (≤75%) reduction in lesion number by 57 days. Also, the researchers compared the active and placebo groups in terms of the lesion recurrence rate at 1 year.

In trial 1, complete clearance occurred in 44% of patients randomly assigned to tirbanibulin 1% ointment vs 5% of patients assigned to vehicle control (difference, 40 percentage points; 95% CI, 32-47; P <.001). A greater percentage of patients assigned to tirbanibulin in the second trial also experienced complete clearance (54% vs 13%; 95% CI, 33-51; P <.001).

A pooled analysis of the 2 trials showed completed clearance occurred in 49% of patients assigned to tirbanibulin vs 9% of patients randomized to vehicle (95% CI, 35-47).

The rates of partial clearance were also significantly higher in the tirbanibulin groups in trial 1 (68% vs 16%; 95% CI, 43-60; P <.001) and trial 2 (76% vs 20%; 95% CI, 48-65; P <.001).

A total of 124 patients who received tirbanibulin developed1 or more lesions in the application area during the 1-year follow-up period. Approximately 58% of these patients had recurrent lesions, and 42% had only new lesions.

Local reactions most commonly attributed to the active treatment included erythema (91%) and flaking or scaling (82%). Adverse events associated with tirbanibulin included application-site pain (10%) and pruritus (9%).

According to the researchers, a limitation of the trials were the incidences of local reactions, which could have made the investigators aware of the group assignments.

The researchers concluded that “larger and longer trials are necessary to determine the effects and risks of tirbanibulin therapy among patients with actinic keratosis.”

Disclosure: This clinical trial was supported by Athenex. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Blauvelt A, Kempers S, Lain E, et al. Phase 3 trials of tirbanibulin ointment for actinic keratosis. N Engl J Med. 2021;384(6):512-520. doi:10.1056/NEJMoa2024040