January 30, 2020: UK and Europe suspend the marketing of Picato® Gel.
The Regulatory Agency for Medicines and Health Products, United Kingdom [1] and the European Medicines Agency (EMA) [2] have announced that the marketing of Picato® Gel containing ingenol mebutate has been discontinued. They have recommended that patients stop using the product pending an investigation into its safety with regard to the skin. Cancer.
See more:
European marketing of Picato is suspended while the risk of skin cancer is reviewed. January 17, 2020. Medscape Medical News.
Class 2 Drug Recall: LEO Laboratories Ltd, Picato 150 mcg / g gel. January 27, 2020. Gov.UK
Introduction
The FDA approval for the use of ingenol mebutate gel was based on data from four Phase III studies in more than 1,000 people showing that ingenol mebutate gel applied once a day for two to three consecutive days is significantly more effective than placebo in the clearing actinic keratosis.
Actinic keratosis of the face and scalp
In two double-blind, vehicle-controlled clinical trials, 547 adult subjects with actinic keratosis on the face or scalp were randomized to treatment with ingenol mebutate gel, 0.015%, or vehicle gel for 3 consecutive days, followed by a follow-up period 8 weeks.
Studies included subjects with 4 to 8 clinically typical, visible, discreet actinic keratoses within 25 cm2 adjoining 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 of 64 years). Approximately 85% of the subjects were male, and all subjects treated with ingenol mebutate were Caucasian.
Effectiveness was evaluated on day 57. The complete elimination rate was defined as the proportion of subjects without clinically visible actinic keratoses in the treatment area.
The partial clearance rate was defined as the proportion of subjects with a reduction of 75% or more in the number of actinic keratosis lesions in base in the selected treatment area.
The key results are tabulated below.
| Study 1 | Study 2 | |||
|---|---|---|---|---|
| Ingenol Mebutate Gel, 0.015% (n = 135) | Vehicle (n = 134) | Ingenol Mebutate Gel, 0.015% (n = 142) | Vehicle (n = 136) | |
| General full dispatch on day 57 | 50 (37%) | 3 (2%) | 67 (47%) | 7 (5%) |
| General partial clearance on day 57 | 81 (60%) | 9 (7%) | 96 (68%) | 11 (8%) |
| Complete removal of lesions of the scalp (day 57) | 4/26 (15%) | 0/25 (0%) | 9/31 (29%) | 1/25 (4%) |
| Complete removal of facial injuries (day 57) | 46/109 (42%) | 3/109 (2%) | 58/111 (52%) | 6/111 (5%) |
- Subjects who achieved complete clearance on day 57 in Study 1 and Study 2 entered a 12-month follow-up period.
- Based on 108 subjects treated with ingenol mebutate gel who achieved complete clearance in Study 1 and Study 2, the reappearance the 12-month rate was 54%.
- Recurrence was defined as the percentage of subjects with any actinic keratosis identified in the previously treated area who achieved complete clearance on day 57.
Actinic keratosis of the trunk and extremities.
In two vehicle-controlled double-blind clinical trials, 458 adult subjects with actinic keratosis on the trunk or limbs were randomized to treatment with ingenol mebutate gel, 0.05%, or vehicle gel for 2 consecutive days, followed by follow-up 8 weeks. -now. Studies included subjects with 4 to 8 discrete, clinically typical actinic keratosis lesions visible within a 25 cm range.2 adjoining 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 the subjects were male, and all subjects treated with ingenol mebutate were Caucasian.
Complete and partial clearance rates were defined as in Study 1.
The key results are tabulated below.
| Study 3 | Study 4 | |||
|---|---|---|---|---|
| Ingenol Mebutate Gel, 0.05% (n = 126) | Vehicle (n = 129) | Ingenol Mebutate Gel, 0.05% (n = 100) | Vehicle (n = 103) | |
| General full dispatch on day 57 | 35 (28%) | sixty-five%) | 42 (42%) | 5 (5%) |
| General partial clearance on day 57 (≥75%) | 56 (44%) | 9 (7%) | 55 (55%) | 7 (7%) |
| Complete clearance (CR) arm injuries (day 57) | 22/84 (26%) | 4/82 (5%) | 27/59 (46%) | 3/67 (5%) |
| Hand injuries from CR (day 57) | 4/25 (16%) | 0/29 (0%) | 6/28 (21%) | 0/27 (0%) |
| CR chest injuries (day 57) | 8/9 (89%) | 1/8 (13%) | 3/5 (60%) | 1/3 (33%) |
| CR (leg / shoulder / back) | 1/8 (13%) | 1/10 (10%) | 6/8 (75%) | 1/6 (17%) |
- Subjects who achieved complete clearance on day 57 in Study 4 entered a 12-month follow-up period. Based on 38 subjects treated with ingenol mebutate gel 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 keratosis. injury in the previously treated area that achieved complete cleaning on day 57.
No long-term animal studies have been conducted to assess the carcinogenic ingenol mebutate potential.
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% was 65 years of age or older and 21% was 75 years of age or older.
- No overall differences in safety or effectiveness were observed between these subjects and the younger subjects.
More information
Return to the page on ingenol mebutate gel.
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