resolved. Few participants experienced erosions/ulcerations or vesiculation/pustulation and none were greater than mild (Grade 2) in severity. In both cohorts, LSRs began by day 2, peaked by the end of treatment, and returned to baseline or resolved by day 29. Slightly more participants in the 5-day cohort experienced LSRs compared with the 3-day cohort. Maximal post-baseline LSR grades are provided to show the highest LSR grade assessed by the investigators regardless of visit in Table 4. Representative photographs of typical and maximal LSRs for both studies are presented in Figure 3.
Pharmacokinetics
Phase 2 study results demonstrated that tirbanibulin was minimally absorbed following 3 or 5 consecutive days of treatment. For the majority of plasma samples collected, tirbanibulin was below the lower limit of quantification of 0.1 ng/mL. The maximum individual plasma concentration across both cohorts and all days of pharmacokinetics sampling did not surpass 2 ng/mL.
DISCUSSION
AK is very common and a major health concern due to its progression to non-melanoma skin cancers such as iSCC.6,14,18 Treatment is generally encouraged as predicting which AK lesion will become cancerous is difficult.6 Commonly used topical therapies include 5-fluorouracil, that is a cytotoxic agent, imiquimod, that acts by immunomodulation, and ingenol mebutate, that induces cell necrosis and inflammation.8-10 These treatments often lead to moderate-to-severe application-site reactions or LSRs (itching, burning, erythema, flaking/crusting, edema, induration, excoriation, erosion, and ulceration),8-10 and negatively impact treatment compliance and patients’ quality of life.5,19 Additionally, 5-fluorouracil (twice daily for 2–4 weeks) and imiquimod (twice weekly for ≤16 weeks) require long treatment durations,8,9 which may prolong patient discomfort from local adverse reactions at both AK lesions and uninvolved areas. Thus, development of an effective and more tolerable topical AK treatment of short duration, having a new targeted mechanism of action, is needed to improve compliance that may lead to better treatment outcomes.
Tirbanibulin ointment 1% is a topical formulation of a novel synthetic molecule that has potent antiproliferative activity against keratinocyte growth in vitro based on inhibition of tubulin polymerization and Src kinase signalling. The reported studies were early-phase development of tirbanibulin ointment 1% in AK among participants with typical demographics and disease characteristics of the target population. Collectively, these studies showed that, firstly, short courses of tirbanibulin ointment 1% are active in reducing AK lesions in multiple locations. Secondly, the low incidence of severe local reactions may serve to differentiate tirbanibulin ointment from other topical treatments for AK. Lastly, these studies supported the
Tirbanibulin ointment 1% is a topical formulation of a novel synthetic molecule that has potent antiproliferative activity against keratinocyte growth in vitro based on inhibition of tubulin polymerization and Src kinase signalling. The reported studies were early-phase development of tirbanibulin ointment 1% in AK among participants with typical demographics and disease characteristics of the target population. Collectively, these studies showed that, firstly, short courses of tirbanibulin ointment 1% are active in reducing AK lesions in multiple locations. Secondly, the low incidence of severe local reactions may serve to differentiate tirbanibulin ointment from other topical treatments for AK. Lastly, these studies supported the
