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FDA Approved Drugs » 2012
Medical Areas: Dermatology | Oncology | Family Medicine

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Picato (ingenol mebutate) gel

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company: LEO Pharma
Approval Status: Approved January 2012
Treatment Area: actinic keratosis

General Information

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 lesions is unknown.

Picato is specifically indicated for the topical treatment of actinic keratosis of the face, scalp, trunk and extremities.

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

Clinical Results

FDA Approval

The FDA approval of Picato for actinic keratosis 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% or vehicle gel for three consecutive days, followed by an 8 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% 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% of the Picato treatment arm and 2% of the vehicle arm. Partial clearance was reached by 60% of the Picato arm and 7% of the placebo arm. Study Two: Complete clearance was reached by 47% of the Picato treatment arm and 5% of the vehicle arm. Partial clearance was reached by 68% of the Picato arm and 8% 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% and 0% and Face 42% and 2% for the Picato and vehicle arms, respectively. Study Two: Scalp 29% and 4% and Face 52% and 5% 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%.

The FDA approval of Picato for actinic keratosis 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% or vehicle gel for two consecutive days, followed by an 8 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% 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% of the Picato treatment arm and 5% of the vehicle arm. Partial clearance was reached by 44% of the Picato arm and 7% of the placebo arm. Study Four: Complete clearance was reached by 42% of the Picato treatment arm and 5% of the vehicle arm. Partial clearance was reached by 55% of the Picato arm and 7% 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%.

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

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 AK lesions is unknown.

Literature References

Rosen RH, Gupta AK, Tyring SK Dual mechanism of action of ingenol mebutate gel for topical treatment of actinic keratoses: Rapid lesion necrosis followed by lesion-specific immune response. Journal of the American Academy of Dermatology 2011 Nov 4

Anderson L, Schmieder GJ, Werschler WP, Tschen EH, Ling MR, Stough DB, Katsamas J Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis. Journal of the American Academy of Dermatology 2009 Jun;60(6):934-43

Siller G, Gebauer K, Welburn P, Katsamas J, Ogbourne SM PEP005 (ingenol mebutate) gel, a novel agent for the treatment of actinic keratosis: results of a randomized, double-blind, vehicle-controlled, multicentre, phase IIa study. The Australasian Journal of Dermatology 2009 Feb;50(1):16-22.

Additional Information

For additional information regarding Picato or actinic keratosis, please visit the LEO Pharma web page.