Mechanism of Action

Picato is a topical gel formulation of ingenol mebutate, an inducer of apoptosis (cell death). Ingenol mebutate is the active agent in the sap of the Australian plant Euphorbia peplus. The mechanism of action by which Picato gel induces cell death in treating actinic keratosis (AK) lesions is unknown.

Side Effects

Adverse effects associated with the use of Picato may include, but are not limited to, the following:

Local skin reactions

Application site pain

Application site pruritus

Application site irritation

Application site infection

Periorbital edema

Nasopharyngitis

Headache

Dosing/Administration

Picato is supplied as a 0.015 percent or 0.05 percent gel for topical administration. The recommended dose for actinic keratosis on the face and scalp is 0.015 percent applied to the affected area once daily for three consecutive days. The recommended dose for actinic keratosis on the trunk and extremities is 0.05 percent applied to the affected area once daily for two consecutive days.

Clinical Trial Results

FDA Approval

The FDA approval of Picato for AK of the face and scalp was based on two double-blind, vehicle-controlled, clinical trials. A total of 547 adults with AK on the face or scalp were enrolled. All subjects had four to eight clinically typical, visible, discrete AK lesions within a 25-cm2 contiguous treatment area. The subjects were randomized to treatment with either Picato gel, 0.015 percent, or vehicle gel for three consecutive days, followed by an eight-week follow-up period. Efficacy was assessed at Day 57. Complete clearance rate was defined as the proportion of subjects with no clinically visible AK lesions in the treatment area. Partial clearance rate was defined as the proportion of subjects with 75 percent or greater reduction in the number of AK lesions at baseline. The percentage of subjects achieving complete and partial clearance at Day 57 are as follows:

Study One: Complete clearance was reached by 37 percent of the Picato treatment arm and 2 percent of the vehicle arm. Partial clearance was reached by 60 percent of the Picato arm and 7 percent of the placebo arm.

Study Two: Complete clearance was reached by 47 percent of the Picato treatment arm and 5 percent of the vehicle arm. Partial clearance was reached by 68 percent of the Picato arm and 8 percent of the placebo arm. The percentage of subjects achieving complete clearance at Day 57 by anatomical location and by trial are as follows:

Study One: Scalp 15 percent and 0 percent and Face 42 percent and 2 percent for the Picato and vehicle arms, respectively.

Study Two: Scalp 29 percent and 4 percent and Face 52 percent and 5 percent for the Picato and vehicle arms, respectively. Subjects who achieved complete clearance at Day 57 in Study 1 and Study 2 (n=108) entered a 12-month follow-up period. The recurrence rate at 12 months was 54 percent.

The FDA approval of Picato for AK of the trunk and extremities was based on two double-blind, vehicle-controlled clinical trials. A total of 458 adults with AK on the trunk or extremities were enrolled. All subjects had with four to eight clinically typical, visible, discrete AK lesions within a 25-cm2 contiguous treatment area. The subjects were randomized to treatment with either Picato gel, 0.05 percent, or vehicle gel for two consecutive days, followed by an eight-week follow-up period. Efficacy was assessed at Day 57. Complete clearance rate was defined as the proportion of subjects with no clinically visible AK lesions in the treatment area. Partial clearance rate was defined as the proportion of subjects with 75 percent or greater reduction in the number of AK lesions at baseline. The percentage of subjects achieving complete and partial clearance at Day 57 are as follows:

Study Three: Complete clearance was reached by 28 percent of the Picato treatment arm and 5 percent of the vehicle arm. Partial clearance was reached by 44 percent of the Picato arm and 7 percent of the placebo arm.

Study Four: Complete clearance was reached by 42 percent of the Picato treatment arm and 5 percent of the vehicle arm. Partial clearance was reached by 55 percent of the Picato arm and 7 percent of the placebo arm. Subjects who achieved complete clearance at Day 57 in Study 4 entered a 12-month follow-up period. Based on 38 Picato gel-treated subjects who achieved complete clearance in Study 4, the recurrence rate at 12 months was 50 percent.