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Treating Actinic Keratosis: Insights from a Phase 3 Trial on Tirbanibulin

Treating Actinic Keratosis: Insights from a Phase 3 Trial on Tirbanibulin

Lain_headshotTed Lain, MD, MBA, is chief medical officer of Sanova Dermatology, based in Texas and Louisiana. Dr Lain spoke with The Dermatologist about the results of a recent phase 3 trial evaluating tirbanibulin as a treatment for actinic keratosis (AK), of which he was an investigator.1

Based on the early data, what types of patients may be good candidates for treatment with tirbanibulin?

In the trial, we demonstrated not only great efficacy but also great tolerability among patients who had four to eight lesions on the face or scalp treated with tirbanibulin. Except for patients who have a history of allergy to any of the components in tirbanibulin ointment, I believe all patients with AKs are candidates for this treatment. Anyone with precancerous lesions on the face or scalp, in my view, are good candidates for field therapy, and tirbanibulin appears to be a safe option after phase 1, 2, and 3 trials.1,2

How does the AK recurrence rate compare with other currently available field treatments?

We want to be extra careful to correctly define what AK recurrence rate is here. The FDA required the trial to define recurrence as those precancerous AKs that were present at baseline and again at the 1 year follow up.1

The estimated recurrence rates for the two identical, double-blind phase 3 trials were approximately 47% at 1 year. Although there have not been any head-to-head trials that compare this rate with other currently available field therapies, I am not concerned about the recurrence rate with tirbanibulin. The current evidence points to favorable outcomes.1,2

What concerns might dermatologists have regarding local site reactions (LSRs) to tirbanibulin, such as erythema, flaking or scaling, and pruritus?

In the trial, we were not allowed to treat the LSRs with anything beyond a bland moisturizer. Therefore, based on our experience within the protocol, I do not have any clinical pearls to minimize or reduce the LSRs. However, we do know that the composite peak LSR occurred at day 8, three days after completing application of tirbaniulin ointment. Even then, that peak composite LSR was low, with the vast majority being mild to moderate in intensity.

While the LSRs peaked by day 8, they resolved quickly, as seen in the day 15 and day 29 data from the pivotal trials. Therefore, while I do not have pearls to offer to mitigate the LSRs, the fact that they occured a few days after completing the course of application, as well as that the intensity in the majority of patients was mild to moderate, makes me less concerned about addressing these in my patients. In fact, since the LSRs were so low, I think patients who have experience using other field therapy agents may be surprised at how minimal of a reaction they may experience with tirbanibulin.

When it comes to AKs, what is your favorite pearl?

I think tirbanibulin offers us a great new alternative with a new mechanism of action to use for field therapy. Certainly, we can consider combining cryodestruction of an individual lesion in the clinic along with tirbanibulin at home for field therapy. Although we have no trial data for that, we do have data that this works with other agents.

I think combining modalities may be the most effective way for both treating the individual lesions as well as reducing the actinic damage of the treated area for clinicians.

Is there anything else notable about AKs or tirbanibulin that you would like to share?

Tirbanibulin has a novel mechanism of action. It inhibits tubulin polymerization, thereby promoting apoptosis in proliferating cells, such as those present in AK. While the exact way that tirbanibulin works to treat precancers is unknown, we know that this mechanism of action is novel.

We also know that the LSRs that occurred during therapy in the pivotal trials show great tolerability. I think it is important for clinicians to understand that this novel mechanism of action may translate into improved tolerability. The tolerability of tirbanibulin means that, what clinicians and patients are used to seeing with other field therapy agents in terms of erythema, scaling, and crusting, they probably will not see with tirbanibulin. That should not be a concern. That is just an advancement of the science.

1. Blauvelt A, Kempers S, Lain E, et al. Phase 3 trials of tirbanibulin ointment for actinic keratosis. N Engl J Med. Published online February 11, 2021. doi:10.1056/NEJMoa2024040
2. Kempers S, DuBois J, Forman S, et al. Tirbanibulin ointment 1% as a novel treatment for actinic keratosis: phase 1 and 2 results. J Drugs Dermatol. 2020;19(11):1093-1100. doi:10.36849/JDD.2020.5576

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