Klisyri (Tirbanibulin)

What Is Klisyri and What Is It Used For?

Klisyri (tirbanibulin) is a topical ointment prescribed for the treatment of mild actinic keratosis on the face and scalp in adults. Actinic keratosis consists of rough, scaly patches of sun-damaged skin that have the potential to develop into squamous cell carcinoma if left untreated.

Actinic keratosis (AK), also known as solar keratosis, is one of the most common dermatological conditions worldwide. It develops in areas of skin that have been subjected to cumulative ultraviolet (UV) radiation exposure over many years. The condition predominantly affects fair-skinned individuals over the age of 50, though it can occur in younger adults with significant sun exposure. Typical locations include the face, scalp (particularly in bald or balding individuals), ears, forearms, and the backs of the hands.

The clinical significance of actinic keratosis lies in its potential for malignant transformation. While most individual AK lesions remain benign, a proportion – estimated at 0.025% to 16% per lesion per year according to various studies – can progress to invasive squamous cell carcinoma (SCC). For this reason, dermatological guidelines from the European Academy of Dermatology and Venereology (EADV), the British Association of Dermatologists (BAD), and the American Academy of Dermatology (AAD) recommend treatment of actinic keratosis rather than a wait-and-see approach, particularly when multiple lesions are present in a field of sun-damaged skin.

Klisyri contains tirbanibulin, a first-in-class small molecule that exerts its therapeutic effect through a novel dual mechanism of action. It simultaneously inhibits two key cellular pathways involved in the abnormal growth of keratinocytes characteristic of actinic keratosis. First, tirbanibulin blocks tubulin polymerisation, disrupting the formation of microtubules essential for cell division. Second, it inhibits signalling through the Src kinase pathway, which is overactivated in actinic keratosis lesions and promotes cell survival and proliferation. By targeting both pathways simultaneously, tirbanibulin triggers antiproliferative and proapoptotic effects, leading to the elimination of dysplastic keratinocytes.

Klisyri was approved by the European Medicines Agency (EMA) in July 2021 and by the U.S. Food and Drug Administration (FDA) in December 2020. It was developed by Athenex, Inc. and is marketed by Almirall, S.A. The approval was based on results from two Phase III randomised, double-blind, vehicle-controlled clinical trials (KX01-AK-003 and KX01-AK-004) involving a total of 702 adult patients with actinic keratosis on the face or scalp.

What Should You Know Before Using Klisyri?

Before using Klisyri, inform your doctor about all medical conditions, especially immune system disorders, pregnancy or breastfeeding plans, and any current medications. The ointment is for external use only and must not be applied to open wounds, inside the nose or ears, or on the lips.

Contraindications

You should not use Klisyri if you are allergic to tirbanibulin or any of the other ingredients in the ointment (propylene glycol and glycerol monostearate 40-55). Signs of an allergic reaction may include severe itching, rash, swelling of the face or throat, or difficulty breathing. If you experience any of these symptoms, stop using the ointment immediately and seek medical attention.

Warnings and Precautions

Talk to your doctor or pharmacist before using Klisyri if any of the following apply to you:

• Previous skin treatments: Do not use Klisyri until the treatment area has fully healed from any previous medication, procedure, or surgical treatment. Applying the ointment to compromised skin may increase the risk of local reactions and systemic absorption
• Open wounds or broken skin: Do not apply Klisyri to open wounds, cuts, or damaged skin. The ointment is designed for application to intact skin only
• Immune system disorders: Tell your doctor if you have problems with your immune system (immunocompromised patients), as the safety and efficacy of Klisyri have not been specifically studied in this population
• Eye contact: If the ointment accidentally gets into your eyes, rinse thoroughly with large amounts of water and seek medical attention promptly
• Internal application: Do not apply the ointment inside the body, inside the nostrils, inside the ears, or on the lips. If the ointment accidentally contacts any of these areas, remove it by rinsing with water

After applying Klisyri, you should take the following precautions:

• Avoid activities that cause heavy sweating
• Avoid sun exposure (including sunlamps and tanning beds) as much as possible; wear protective clothing and a hat when outdoors
• Do not cover the treated area with bandages or dressings
• Do not apply more ointment than your doctor has directed
• Do not apply more than once daily
• Do not let other people or pets touch the treated area for approximately 8 hours after application; if the area is touched, the body part that made contact should be washed

Pregnancy and Breastfeeding

Klisyri should not be used during pregnancy. Although systemic absorption of tirbanibulin is minimal following topical application, adequate data on its use in pregnant women are not available. If you are pregnant, think you may be pregnant, or are planning to have a baby, consult your doctor before using this medicine. Your doctor will discuss alternative treatments that may be more appropriate during pregnancy.

It is not known whether tirbanibulin passes into breast milk. If you are breastfeeding, your doctor will help you weigh the benefits of treatment against any potential risk to your baby. Given the very low systemic exposure from topical application, the risk is considered to be minimal, but a decision should be made by your treating physician.

Children and Adolescents

Klisyri should not be used in children and adolescents under 18 years of age. Actinic keratosis is a condition that results from decades of cumulative sun exposure and does not occur in the paediatric population. There are no data on the use of tirbanibulin in this age group.

Driving and Operating Machinery

Klisyri is not expected to have any effect on your ability to drive or use machines. The drug acts locally in the skin, and systemic exposure is minimal. No studies have reported cognitive or neurological side effects that could impair driving performance.

How Does Klisyri Interact with Other Drugs?

Klisyri has minimal systemic absorption when applied topically, which greatly limits the potential for systemic drug interactions. However, you should tell your doctor about all medications you are using, including other topical skin treatments, to avoid applying multiple products to the same area.

Because tirbanibulin is applied topically and has very low systemic absorption, the likelihood of clinically significant interactions with oral or injectable medications is extremely low. In clinical pharmacokinetic studies, plasma concentrations of tirbanibulin were very low or below the limit of detection following topical application of the 1% ointment to a 25 cm² area for 5 days. This negligible systemic exposure means that the drug is unlikely to interact with hepatic cytochrome P450 enzymes or other systemic drug-metabolising pathways.

However, there are several important considerations regarding concomitant use of other products:

Topical Product Interactions

Avoid applying other topical products (including cosmetics, sunscreens, moisturisers, or other prescription or over-the-counter skin treatments) to the treated area during the 5-day treatment period. Using other products on the same area may alter the absorption or effectiveness of Klisyri, or may exacerbate local skin reactions. If you need to use sunscreen, apply it to areas of the face and scalp that are not being treated with Klisyri.

Previous Topical Treatments

If you have previously used other topical treatments for actinic keratosis – such as fluorouracil (5-FU), imiquimod, diclofenac, or photodynamic therapy – ensure the treated area has fully healed before starting Klisyri. Applying Klisyri to skin that has not recovered from a prior treatment could intensify local reactions and compromise the therapeutic outcome. Your doctor will advise on the appropriate waiting period.

If you have previously used Klisyri or similar medicines for actinic keratosis, tell your doctor before starting a new course of treatment. Your doctor will assess the treated area and determine whether a repeat course or an alternative approach is most appropriate.

What Is the Correct Dosage of Klisyri?

Apply a thin layer of Klisyri ointment to the affected area once daily for 5 consecutive days. Each single-use sachet contains 250 mg of ointment (2.5 mg tirbanibulin), which is sufficient to treat an area of up to 25 cm² on the face or scalp.

Always use Klisyri exactly as your doctor has told you. If you are unsure, check with your doctor or pharmacist. The treatment consists of a single 5-day cycle of once-daily application. Do not extend the treatment beyond 5 days unless specifically instructed by your doctor.

Adults

Step-by-Step Application Instructions

1. Wash your hands thoroughly with soap and water before applying the ointment
2. Clean the affected area with mild soap and water and gently pat dry
3. Open a new sachet each time by tearing along the perforation
4. Squeeze a small amount of ointment onto your fingertip
5. Apply a thin, even layer over the entire affected area on the face or scalp
6. Wash your hands immediately with soap and water after application
7. Do not wash or touch the treated area for approximately 8 hours. After 8 hours, you may gently wash the area with mild soap and water
8. Do not cover the treated area with bandages or dressings
9. Repeat at approximately the same time each day for all 5 treatment days

Elderly Patients

No dose adjustment is required for elderly patients. Since actinic keratosis is most prevalent in older adults, the majority of patients in clinical trials were over the age of 65. The safety and efficacy profiles were consistent across age groups, and no additional precautions are necessary beyond those applicable to all adult patients.

Children

Klisyri is not indicated for use in children and adolescents under 18 years of age. Actinic keratosis does not occur in this population.

Missed Dose

If you miss a dose, apply the ointment as soon as you remember and then continue with your regular schedule. Do not apply the ointment more than once per day to compensate for a missed dose. If you miss multiple doses, consult your doctor about whether to extend the treatment course or consider alternative options.

Overdose

If you apply too much Klisyri, wash the treated area with mild soap and water. Excessive application may increase the severity of local skin reactions such as redness, swelling, and irritation. Contact your doctor or pharmacist if you develop severe skin reactions after over-application. In the unlikely event that Klisyri is accidentally swallowed, drink plenty of water and seek medical attention immediately, bringing the packaging with you.

What Are the Side Effects of Klisyri?

The most common side effects of Klisyri are local skin reactions at the application site, including redness, flaking, crusting, swelling, and skin erosion. These are expected effects of the treatment and typically peak around day 8 and resolve within 2–3 weeks after the 5-day course is completed.

Like all medicines, Klisyri can cause side effects, although not everybody gets them. The side effects are predominantly localised to the area where the ointment has been applied. Because Klisyri works by destroying abnormal skin cells, some degree of local skin reaction is an expected and indeed necessary part of the treatment process. Understanding this can help you manage expectations during and after treatment.

In the two pivotal Phase III clinical trials (KX01-AK-003 and KX01-AK-004), local skin reactions were assessed using a composite Local Skin Reaction (LSR) grading scale. The majority of patients experienced some degree of local reaction, with the peak severity occurring at approximately day 8 (3 days after the last application). In most patients, the reactions resolved to mild or minimal levels by day 29 (approximately 3 weeks after starting treatment) and fully resolved by day 57.

Managing Local Skin Reactions

Local skin reactions are a normal part of the Klisyri treatment process and generally do not require you to stop the treatment. However, the following strategies may help you manage discomfort:

• Avoid irritants: Do not apply cosmetics, sunscreens, or other topical products to the treated area during the treatment period and for at least a few days after completing the course
• Protect from the sun: Keep the treated area covered with protective clothing and avoid direct sun exposure, as UV radiation can worsen inflammation
• Gentle cleansing: After the 8-hour contact period, wash the area gently with mild soap and lukewarm water. Avoid scrubbing or using harsh cleansers
• Moisturise after treatment: Once the acute reaction phase has subsided (typically after 1–2 weeks post-treatment), a gentle, fragrance-free moisturiser may help the skin recover
• Contact your doctor if reactions become severe – for example, if you experience extensive blistering, intense pain, or signs of infection (increasing warmth, pus, fever)

It is important to understand that the absence of local skin reactions does not indicate that the treatment has failed to work. Some patients experience milder reactions than others. The efficacy of Klisyri should be assessed by your doctor at the follow-up visit approximately 8 weeks after treatment.

Reporting Side Effects

It is important to report suspected side effects after a medicine has been approved. This helps in the continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients are encouraged to report any suspected adverse reactions to their national pharmacovigilance authority or through the relevant reporting system in their country.

How Should You Store Klisyri?

Store Klisyri at room temperature, protected from cold. Do not freeze. Keep out of the sight and reach of children. Each sachet is for single use only – discard any unused ointment.

Proper storage is essential to maintain the effectiveness and safety of Klisyri. Follow these guidelines:

• Temperature: Store at room temperature. Protect from cold. Do not refrigerate and do not freeze, as extreme cold may alter the ointment formulation
• Keep out of reach of children: Store in a location that children cannot access
• Check the expiry date: Do not use Klisyri after the expiry date stated on the outer carton and sachet label after “EXP”. The expiry date refers to the last day of that month
• Single use only: Each sachet is intended for one application only. Do not save an opened sachet to reuse another day, even if ointment remains inside
• Disposal: Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use, to help protect the environment

What Does Klisyri Contain?

Each single-use sachet of Klisyri contains 250 mg of white to off-white ointment. The active substance is tirbanibulin (2.5 mg per sachet, equivalent to 10 mg per gram of ointment). The ointment also contains propylene glycol and glycerol monostearate 40-55 as inactive ingredients.

Active Ingredient

The active substance in Klisyri is tirbanibulin. Each single-use sachet contains 2.5 mg of tirbanibulin in 250 mg of ointment. The concentration is 10 mg per gram (1% w/w). Tirbanibulin is a synthetic small molecule that acts as a dual inhibitor of tubulin polymerisation and the Src proto-oncogene tyrosine kinase signalling pathway.

Inactive Ingredients (Excipients)

The other ingredients in Klisyri are:

• Propylene glycol: A common pharmaceutical excipient used as a solvent and to improve the consistency of the ointment. Propylene glycol may cause mild skin irritation in some individuals
• Glycerol monostearate 40-55: An emulsifier that helps maintain the uniform consistency of the ointment formulation

Packaging and Appearance

Each sachet contains 250 mg of white to off-white ointment. Klisyri is supplied in cartons containing 5 single-use sachets made of polyethylene/aluminium foil, providing enough medication for the complete 5-day treatment course. The sachets are designed with a perforation for easy opening.

How Does Klisyri Work? (Mechanism of Action)

Klisyri works through a novel dual mechanism: it simultaneously inhibits tubulin polymerisation (disrupting cell division) and Src kinase signalling (blocking cell growth and survival signals), leading to the selective death of abnormal keratinocytes in actinic keratosis lesions.

Tirbanibulin represents a new class of topical treatment for actinic keratosis, combining two distinct antiproliferative mechanisms in a single molecule. This dual mechanism of action distinguishes it from existing topical therapies and contributes to its clinical efficacy.

Tubulin Polymerisation Inhibition

Tubulins are proteins that polymerise to form microtubules, which are essential components of the cell’s cytoskeleton and play a critical role in cell division (mitosis). During mitosis, microtubules form the mitotic spindle, which is responsible for segregating chromosomes equally between daughter cells. Tirbanibulin binds to tubulin and prevents its polymerisation into microtubules. This disrupts the formation of the mitotic spindle, arresting cell division and triggering programmed cell death (apoptosis) in rapidly dividing abnormal keratinocytes.

Src Kinase Pathway Inhibition

The Src family of tyrosine kinases are non-receptor kinases that play a central role in cellular growth, differentiation, and survival signalling. In actinic keratosis, the Src kinase pathway is often overactivated, promoting the survival and proliferation of dysplastic keratinocytes. Tirbanibulin inhibits Src kinase signalling, thereby reducing the pro-survival signals in abnormal cells. This effect complements the anti-mitotic action by simultaneously removing both the proliferative drive and the survival advantage of AK cells.

Together, these dual mechanisms create a targeted approach that selectively eliminates the abnormal cells of actinic keratosis while minimising damage to surrounding normal tissue. The result is a concentrated, field-directed treatment that addresses both established lesions and subclinical areas of dysplasia within the treated field.

Clinical Evidence

The efficacy of Klisyri was demonstrated in two Phase III, randomised, double-blind, vehicle-controlled trials involving 702 adults with 4 to 8 clinically typical, visible, non-hypertrophic, non-hyperkeratotic actinic keratosis lesions on the face or scalp within a contiguous 25 cm² area. The primary endpoint was complete clearance (100% reduction in the number of AK lesions) at day 57.

Results showed that Klisyri achieved complete clearance rates of 44% and 54% in the two trials, compared with 5% and 13% for vehicle control, respectively (p<0.001 for both). Partial clearance (≥75% reduction in lesion count) was achieved in 68% and 76% of Klisyri-treated patients. These clearance rates are clinically meaningful and comparable to other established topical treatments for actinic keratosis.

Frequently Asked Questions About Klisyri