Newly published data confirm that daily topical tirbanibulin (Klisyri) was effective at treating actinic keratosis lesions on the face and scalp in two phase III trials.
In two identical double-blind trials looking at a total of 702 patients, tirbanibulin 1% ointment that was applied once daily for five days resulted in roughly half of patients achieving complete lesion clearance versus a placebo ointment (49% vs 9%), Andrew Blauvelt, MD, of the Oregon Medical Research Center in Portland, and colleagues reported in the New England Journal of Medicine.
The trials were the principal basis for the product’s FDA approval in December.
Specifically, 44% (77 of 175) of patients on tirbanibulin in the first trial — which include 351 patients total — achieved complete clearance of actinic keratoses at day 57 versus only 5% (eight of 176) of those on the vehicle ointment (difference 40 percentage points, 95% CI 32-47, P<0.001).
And in the second trial, which also included a total of 351 patients, 54% (97 of 178 patients) of those on tirbanibulin achieved complete lesion clearance versus only 13% (22 of 173) of the placebo group (difference 42 percentage points, 95% CI 33-51, P<0.001).
Significantly more patients also achieved partial reduction in the number of lesions, defined as up to 75% reduction. This occurred in 68% and 76% of patients in the tirbanibulin groups in the first and second trials, respectively.
By day 57, those on tirbanibulin saw a median 83% and 100% reduction in the overall number of lesions within the treatment area compared with baseline in trials one and two, respectively.
“Tirbanibulin ointment is a novel anti-proliferative agent that inhibits tubulin polymerization and disrupts Src kinase signaling, and has the potential to inhibit growth of abnormal skin cells in actinic keratosis,” said study co-author Jane Fang, MBBS, of Athenex, which developed the agent. (Almirall, which announced the product’s FDA approval, is responsible for marketing it.)
“Currently approved topical treatments require weeks or months of application and may lead to intolerable side effects that undermine compliance and reduce efficacy of treatment,” Fang told MedPage Today.
These phase III findings build upon earlier phase I and phase II trial data, which also showed efficacy of tirbanibulin ointment against actinic keratosis on the dorsal forearm in addition to the face and scalp.
“Actinic keratosis is a very common precancerous skin condition that affects about 58 million people in the U.S. and has a rising incidence as the nation’s population ages,” Fang added. “Most commonly affected people are older — over 40 years old — men with fair skin type who have been exposed to years of sun or UV damage…. As there is a risk of 0.025%-16% per year for each actinic keratosis to progress to skin cancer and it is not possible to predict which actinic keratosis will become cancerous, early treatment of actinic keratosis is generally recommended.”
The trials included adults with actinic keratoses on the face or scalp. They were instructed to self-apply the ointment to a 25-cm2 contiguous area containing four to eight lesions once daily for 5 consecutive days.
In terms of adverse events, 92% of those on tirbanibulin experienced some degree of erythema, mostly deemed moderate, and 82% experienced flaking or scaling. Other less common side effects included crusting, swelling, vesiculation or pustulation, as well as erosion or ulceration. No serious adverse events were reported.
“Future clinical trials to address effectiveness and safety of tirbanibulin ointment over larger treatment area, additional treatment courses, and combination treatment in actinic keratosis are being planned,” Fang said. “Expansion of indications for tirbanibulin ointment in the treatment of skin cancers, psoriasis, and genital warts will also be explored.”
The study was funded by Athenex.
Blauvelt reported relationships with AbbVie and consulting fees from Almirall, Arena Pharmaceuticals, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant Sciences, Eli Lilly, Forte Biosciences, Galderma Laboratories, Incyte, Janssen Biotech, LEO Pharma, Novartis, Pfizer, Rapt Therapeutics, Regeneron Pharmaceuticals, Sanofi Genzyme, Sun Pharmaceutical Industries, and UCB Pharma. Fang is an Athenex employee. Other study authors also reported disclosures.