FDA approves first gel for short-term topical AK therapy

FDA approved ingenol mebutate (Picato, LEO Pharma) gel (0.015%, 0.05%) for the topical treatment of actinic keratosis (AK). It is the first topical AK therapy that can be used for as few as 2 or 3 consecutive days.

AK is a precancerous condition caused by cumulative sun exposure that has the potential to progress to squamous cell carcinoma (SCC), the second most common type of skin cancer. Picato 0.015% gel is used once daily on the face and scalp for 3 consecutive days; Picato 0.05% gel is used once daily on the trunk and extremities for 2 consecutive days.

“The approval of Picato gel is very exciting as it will give physicians and health plans an effective 2- or 3-day topical solution for actinic keratosis, which can lead to squamous cell carcinoma,” John Koconis, president and CEO of LEO Pharma, told Formulary.

According to the American Academy of Dermatology (ADD), 1 in 5 Americans will develop skin cancer in the course of their lifetime. Studies show that about 65% of SCCs begin as untreated AK, and guidelines from the AAD estimate that 60% of predisposed persons older than age 40 years have at least 1 actinic keratosis.  

“Since there is no way to predict which actinic keratosis will advance to skin cancer, early detection and treatment of lesions are critical,” said ingenol mebutate study investigator  Mark Lebwohl, MD, department of dermatology, Mount Sinai Medical Center, New York.  “What makes this new solution particularly exciting is the 2- or 3-day course of treatment.”  

In four phase 3 clinical studies of more than 1,000 patients with AK, a significantly higher proportion of those treated with Picato gel (n=503) saw complete clearance of AKs in the field of treatment as compared to placebo (n=502). The most common adverse events were local skin reactions, including erythema, flaking/scaling, crusting, and swelling.  

Picato gel is for topical use only; not for oral, ophthalmic, or intravaginal use. Eye disorders, including severe eye pain, eyelid edema, eyelid ptosis, and periorbital edema, can occur after exposure. Patients should wash hands well after applying Picato gel, and avoid transfer of the drug to the periocular area during and after application. Severe skin reactions in the treated area, including erythema, crusting, swelling, vesiculation/pustulation, and erosion/ulceration, can occur after application. Administration of Picato gel is not recommended until the skin is healed from any previous drug or surgical treatment.

The most common adverse reactions observed in clinical trials (≥2%) are local skin reactions, application-site pain, application-site pruritus, application-site irritation, application-site infection, periorbital edema, nasopharyngitis, and headache.

There are no adequate and well-controlled studies of Picato gel in pregnant women. Picato gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. The safety and effectiveness of Picato gel for AK in patients less than 18 years of age have not been established.