“with transient local reactions,” according to the results of two identically designed trials.
However, the results, assessed at day 57 and out to 1 year of follow-up, were associated with recurrence of lesions at 1 year, noted lead author Andrew Blauvelt, MD, president of the Oregon Medical Research Center, Portland, and colleagues.
“The incidence of recurrence with conventional treatment has ranged from 20% to 96%,” they noted. “Among patients who had complete clearance at day 57 in the current trials, the estimated incidence of recurrence of previously cleared lesions was 47% at 1 year.” At 1 year, they added, “the estimated incidence of any lesions (new or recurrent) within the application area was 73%” and the estimate of sustained complete clearance was 27%.
A total of 700 adults completed the two multicenter, double-blind, parallel-group, vehicle-controlled trials, conducted concurrently between September 2017 and April 2019 at 62 U.S. sites. The results were published in the New England Journal of Medicine.
To be eligible, patients, mostly White men, had to have four to eight clinically typical, visible, and discrete AK lesions on the face or scalp within a contiguous area measuring 25 cm2. They were randomly assigned to treatment with either tirbanibulin 1% ointment or vehicle ointment (containing monoglycerides, diglycerides, and propylene glycol), which they applied once daily to the entire contiguous area for 5 days.
Pooled data across the two trials showed that the primary outcome, complete clearance of all lesions at day 57, occurred in 49% of the tirbanibulin groups versus 9% of the vehicle groups, and partial clearance (the secondary outcome) occurred in 72% versus 18% respectively. For both outcomes, and in both trials, all results were statistically significant.
Of the 174 patients who received tirbanibulin and had complete clearance, 124 had one or more lesions develop within the application area during follow-up, the authors reported. Of these, 58% had recurrences, while 42% had new lesions.
While individual AK lesions are typically treated with cryosurgery, the study authors noted that treatment of multiple lesions involves topical agents, such as fluorouracil, diclofenac, imiquimod, or ingenol mebutate, and photodynamic therapy, some of which have to be administered over periods of weeks or months and “may be associated with local reactions of pain, irritation, erosions, ulcerations, and irreversible skin changes of pigmentation and scarring,” which may reduce adherence.
In contrast, the current studies showed the most common local reactions to tirbanibulin were erythema in 91% of patients and flaking or scaling in 82%, with transient adverse events including application-site pain in 10% and pruritus in 9%.
“Unlike with most topical treatments for actinic keratosis ... severe local reactions, including vesiculation or pustulation and erosion or ulceration, were infrequent with tirbanibulin ointment,” the authors noted. “This could be due to the relatively short, 5-day course of once-daily treatment.”
They concluded that “larger and longer trials are necessary to determine the effects and risks” of treatment with tirbanibulin for treating AK.
Tirbanibulin, a synthetic inhibitor of tubulin polymerization and Src kinase signaling, was approved by the Food and Drug Administration in December 2020, for the topical treatment of AK of the face or scalp.
Asked to comment on the findings, Neal Bhatia, MD, a dermatologist and researcher at Therapeutics Dermatology, San Diego, who was not involved with the study, said that “a treatment with a 5-day course and excellent tolerability will make dermatologists rethink the old practice of ‘freeze and go.’ ”
In an interview, he added, “tirbanibulin comes to the U.S. market for treating AKs at a great time, as ingenol mebutate has been withdrawn and the others are not widely supported. The mechanism of promoting apoptosis and inducing cell cycle arrest directly correlates to the local skin reaction profile of less crusting, vesiculation, and overall signs of skin necrosis as compared to [5-fluorouracil] and ingenol mebutate, which work via that pathway. As a result, there is a direct impact on the hyperproliferation of atypical keratinocytes that will treat visible and subclinical disease.”
“The ointment vehicle is also novel as previous therapies have been in either creams or gels,” he said.
The two trials were funded by tirbanibulin manufacturer Athenex. Dr. Blauvelt reported receiving consulting fees from Athenex and other pharmaceutical companies, including Almirall, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant Sciences. Other author disclosures included serving as a consultant to Athenex and other companies. Several authors are Athenex employees. Dr. Bhatia disclosed that he is an adviser and consultant for Almirall and has been an investigator for multiple other AK treatments.