Key clinical-trial evidence for ingenol mebutate gel

30 January 2020 — UK and Europe suspend the marketing of Picato® Gel.

The Medicines and Healthcare products Regulatory Agency, UK [1] and the European Medicines Agency (EMA) [2] have announced that marketing of Picato® Gel containing ingenol mebutate has been suspended. They have recommended that patients stop using the product pending an investigation into its safety with respect to skin cancer.

See more:

• European Marketing of Picato Suspended While Skin Cancer Risk Reviewed. 17 Jan 2020. Medscape Medical News.
• Class 2 Medicines Recall: LEO Laboratories Ltd, Picato 150 mcg/g gel. 27 Jan 2020. Gov.UK

Introduction

The FDA approval for the use of ingenol mebutate gel was based on data from four Phase III studies in over 1000 people showing that ingenol mebutate gel applied once-daily for two or three consecutive days is significantly more effective than placebo at clearing actinic keratoses.

Actinic keratosis of the face and scalp

In two double-blind, vehicle-controlled, clinical trials, 547 adult subjects with actinic keratoses on the face or scalp were randomised to treatment with either ingenol mebutate gel, 0.015% or vehicle gel for 3 consecutive days, followed by an 8-week follow-up period.

The studies enrolled subjects with 4 to 8 clinically typical, visible, discrete actinic keratoses within a 25 cm² contiguous treatment area.

On each scheduled dosing day, the study gel was applied to the entire treatment area. A total of 536 subjects (98%) completed these studies. Study subjects ranged from 34 to 89 years of age (mean 64 years). Approximately 85% of subjects were male, and all ingenol mebutate-treated subjects were Caucasian.

Efficacy was assessed at day 57. Complete clearance rate was defined as the proportion of subjects with no clinically visible actinic keratoses in the treatment area.

Partial clearance rate was defined as the proportion of subjects with 75% or greater reduction in the number of actinic keratoses lesions at baseline in the selected treatment area.

Key results are tabulated below.

• Subjects who achieved complete clearance at day 57 in Study 1 and Study 2 entered a 12-month follow-up period.
• Based on 108 ingenol mebutate gel-treated subjects who achieved complete clearance in Study 1 and Study 2, the recurrence rate at 12 months was 54%.
• Recurrence was defined as the percentage of subjects with any identified actinic keratosis in the previously treated area who achieved complete clearance at day 57.

Actinic keratosis of the trunk and extremities

In two double-blind, vehicle-controlled clinical trials, 458 adult subjects with actinic keratoses on the trunk or extremities were randomized to treatment with either ingenol mebutate gel, 0.05% or vehicle gel for 2 consecutive days, followed by an 8-week follow-up period. The studies enrolled subjects with 4 to 8 clinically typical, visible, discrete actinic keratoses lesions within a 25 cm² contiguous treatment area. Hypertrophic and hyperkeratotic lesions were excluded from treatment. On each scheduled dosing day, the study gel was applied to the entire treatment area. A total of 447 subjects (98%) completed these studies. Study subjects ranged from 34 to 89 years of age (mean 66 years).

Approximately 62% of subjects were male, and all ingenol mebutate-treated subjects were Caucasian.

Complete and partial clearance rates were defined as in study 1.

Key results are tabulated below.

• Subjects who achieved complete clearance at day 57 in study 4 entered a 12-month follow-up period. Based on 38 ingenol mebutate gel-treated subjects who achieved complete clearance in study 4, the recurrence rate at 12 months was 50%.
• Recurrence was defined as the percentage of subjects with any identified actinic keratoses lesion in the previously treated area who achieved complete clearance at day 57.

Long-term animal studies have not been performed to evaluate the carcinogenic potential of ingenol mebutate.

The effects of ingenol mebutate on fertility have not been evaluated.

Use in the elderly

• Of 1165 subjects treated with ingenol mebutate gel in clinical trials, 56% were 65 years and older and 21% were 75 years and older.
• No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

Further information

Return to the page on ingenol mebutate gel.

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