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

Australas J Dermatol. 2009 Feb;50(1):16-22. doi: 10.1111/j.1440-0960.2008.00497.x.


The sap of the plant Euphorbia peplus is a traditional remedy for skin conditions, including actinic keratosis. The active constituent of the sap is ingenol mebutate (ingenol-3-angelate), formerly known as PEP005. This randomized, double-blind, vehicle-controlled, phase IIa study investigated the safety (and secondarily the efficacy) of two applications of ingenol mebutate gel in 58 patients with biopsy-confirmed actinic keratosis. Five preselected lesions were treated with ingenol mebutate gel, 0.0025%, 0.01% or 0.05%, or vehicle gel, on days 1 and 2 (Arm A) or days 1 and 8 (Arm B). There were no significant differences in tolerability or efficacy between Arms A and B. Treatment was well tolerated. The most common local skin responses were dose-related erythema, flaking/scaling/dryness and scabbing/crusting. Efficacy was greatest with ingenol mebutate gel, 0.05%, which resulted in complete clinical clearance of 71% of treated lesions (P < 0.0001 vs vehicle gel). In addition, 67% of patients treated with ingenol mebutate gel, 0.05% had clinical clearance of at least four of five treated lesions (P = 0.0185 vs vehicle gel). Ingenol mebutate gel is being developed as a short-course topical therapy for actinic keratosis and non-melanoma skin cancer.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Arm / pathology
  • Australia
  • Diterpenes / therapeutic use*
  • Double-Blind Method
  • Drug Administration Schedule
  • Esters / therapeutic use*
  • Face / pathology
  • Female
  • Gels / therapeutic use
  • Humans
  • Keratosis, Actinic / drug therapy*
  • Keratosis, Actinic / pathology
  • Male
  • Middle Aged
  • Scalp / pathology
  • Treatment Outcome


  • 3-ingenyl angelate
  • Antineoplastic Agents, Phytogenic
  • Diterpenes
  • Esters
  • Gels