Therapeutic: tirbanibulin for actinic keratosis

Published: 1-Feb-2021

Actinic keratosis (AK), also known as solar keratosis, is a common chronic, precancerous skin disease

It largely occurs in areas of skin that have had heavy exposure to UV radiation, with the most common sites being the face, ears, bald heads, forearms, backs of hands and the lower legs.

Lesions may develop into squamous cell carcinoma but, as there is no way of telling which will do this, all should be treated.

A treatment, tirbanibulin, has been developed by US biotech, Athenex, and is being commercialised in conjunction with Almirall as a topical treatment for actinic keratosis on the face and scalp.

The drug has a dual mechanism of action: it inhibits both microtubule polymerisation and Src kinase signalling.1

A Phase I/II study has been done.2 In the Phase I part of the trial, 30 AK patients with forearm lesions were treated with 1% tirbanibulin ointment (25 or 100 cm2) for 3–5 days and evaluated to day 45.

Both cohorts experienced reductions in lesions. Then, in the Phase II part, 168 patients with face or scalp lesions were treated with the ointment for 3–5 days (25 cm2) and evaluated to day 57.

Of those treated for 5 days, the complete clearance was seen in 43% of the 5-day cohort, and in 32% of those treated for 3 days.

The most common adverse events were transient mild local erythema, flaking and scaling, plus pruritus and pain. Plasma concentrations of the drug were low or undetectable. The 5-day regimen was chosen for Phase III.

Two vehicle-controlled Phase III clinical studies have also been done. In the two trials, 702 patients with actinic keratosis lesions on the face or scalp were enrolled and treated once a day for 5 days with either the ointment or an active-free vehicle.

The ointment was applied to 25 cm2 of skin, encompassing 4–8 lesions. In one of the studies, 44% patients achieved a 100% clearance of AK lesions in the treated area compared with 5% with the vehicle. In the second, the percentages were 54% and 13%.

More than three quarters of those treated with the ointment reached the secondary endpoint of at least 75% clearance of lesions. It was well tolerated, with the most common adverse being pruritis at the application site, which was experienced by about one in 10 of those treated.

There were no discontinuations resulting from adverse events. The drug is also being evaluated as a potential treatment for acute myeloid leukaemia.3 A trial in prostate cancer was less successful.4


  1. L. Niu, et al., J. Biol. Chem. 294, 18099 (2019).
  2. S. Kempers, et al., J. Drugs Dermatol. 19, 1093 (2020).
  3. M.T. Kasner, et al., J. Clin. Oncol. 35(Suppl.), Abst. 7043 (2017).
  4. E.S. Antonarakis, et al., J. Clin. Oncol. 30(Suppl.), Abst. 4654 (2012).

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