Safety, Tolerability and Efficacy of Tirbanibulin Ointment 1% Treatment on 100 cm2 of the Face and Scalp in Patients with Actinic Keratosis: A Phase 3 Study

Introduction: Tirbanibulin ointment 1% has demonstrated efficacy, tolerability, and safety for AK and is approved in the US and Europe for treating AK on the face or scalp over an area up to 25 cm2 [1]. The objective of this study was to evaluate safety and tolerability of tirbanibulin applied to a larger area, a field of 100 cm2, on the face or balding scalp in adult patients with AK. Methods: A phase 3, multicenter, open-label, single-arm study (NCT05279131) was conducted among adult patients having a treatment field on the face or balding scalp that measured 100 cm2 and contained 4-12 AKs. Patients received tirbanibulin for 5 consecutive days and were evaluated for safety, tolerability, and AK persistence until Day 57. Safety was assessed by evaluating treatment emergent adverse events (TEAEs). Tolerability endpoints included scores, 0 (absent) to 3 (severe), of 6 local signs captured at each timepoint. Exploratory efficacy was measured as percentage change from baseline (CFB) in AK lesion count. Results: A total of 105 patients (20 sites in the US) were included in the safety analysis set (males: 69%; ≥65 years: 65%; Fitzpatrick skin type II: 63%; AK on the face: 68%). Most common local tolerability signs after 100 cm2 tirbanibulin administration were erythema (96% of patients) and flaking/scaling (85%), which were mild-to-moderate in severity, peaked at Day 5 to 8, and resolved or returned to baseline by Day 29. Severe erythema was reported only in 6% of patients and severe flaking/scaling in 9% of patients. Overall, the tolerability profile of treating a 100 cm2 area was consistent with that seen with a 25 cm2 area [1]. Most frequent TEAEs were application site pruritus (11%) and application site pain (9%), consistent with previous Phase 3 study results. No serious TEAEs related to drug were reported. Maximum local tolerability composite score was 4 out of 18, consistent with prior pivotal trials. Patients entered the study with a mean of 7.7 AKs and completed the study with a mean of 1.8 AKs, indicating outstanding efficacy. Mean percentage CFB in lesion count at Day 57 was 78%, consistent with the Phase 3 study with a 25 cm2 treatment area [1]. Conclusions: Safety, local tolerability, and efficacy in patients with AK treated with tirbanibulin over a 100 cm2 area were consistent with those previously reported in patients with AK treated in pivotal trials with tirbanibulin over a smaller area. [1] Blauvelt A et al. N Engl J Med. 2021;384(6):512–20.