• Procedure started
  • Under evaluation
  • PRAC recommendation
  • CHMP opinion
  • European Commission final decision
Current status:
European Commission final decision


Risks of Picato for actinic keratosis outweigh benefits

On 30 April 2020, EMA completed its review of Picato (ingenol mebutate), a gel for treating the skin
condition actinic keratosis, and concluded that the medicine may increase the risk of skin cancer and
that its risks outweigh its benefits.

The review looked at results of a study comparing Picato with imiquimod (another medicine for actinic keratosis). After 3 years, 6.3% of patients treated with Picato (15 out of 240 patients) developed skin cancer, particularly squamous cell carcinoma, in the treated skin area compared with 2% of patients treated with imiquimod (5 out of 244 patients).

Data from other studies with ingenol mebutate or a similar medicine ingenol disoxate, laboratory studies and reports received since the medicine has been on the market were also assessed in the review.

It was noted that recent data from a study on the effectiveness of actinic keratosis treatments supported the previous observation, detailed in the medicine’s product information, that Picato’s effectiveness decreases over time. 

Picato is no longer authorised in the EU as the marketing authorisation was withdrawn on 11 February 2020 at the request of LEO Laboratories Ltd, the company that marketed the medicine.

Key facts

About this medicine
Approved name
International non-proprietary name (INN) or common name

ingenol mebutate

Associated names
About this procedure
Current status
European Commission final decision
Reference number
Article 20 procedures

This type of procedure is triggered for medicines that have been authorised via the centralised procedure in case of quality, safety or efficacy issues.

Decision making model
Authorisation model
Centrally authorised product(s)
Key dates and outcomes
Procedure start date
PRAC recommendation date
CHMP opinion/CMDh position date
EC decision date

All documents

Procedure started

Under evaluation

  • List item

    Picato Article-20 referral - Annex I - Scientific conclusions (PDF/109.95 KB)

    First published: 21/01/2020

  • List item

    Picato Article-20 referral - Assessment report on provisional measures (PDF/3.17 MB)


    First published: 21/01/2020
    Last updated: 04/03/2020

  • List item

    Picato Article-20 referral - EMA suspends Picato as a precaution while review of skin cancer risk continues (PDF/124.3 KB)

    First published: 17/01/2020
    Last updated: 21/01/2020

  • Recommendation provided by Pharmacovigilance Risk Assessment Committee

    European Commission final decision

  • List item

    Picato Article-20 referral - Risks of Picato for actinic keratosis outweigh benefits (PDF/124.18 KB) (updated)

    First published: 30/04/2020
    Last updated: 27/07/2020

  • List item

    Picato Article-20 referral - Annex - Scientific conclusions (PDF/106.21 KB) (new)

    First published: 27/07/2020

  • List item

    Picato Article-20 referral - Assessment report (PDF/2.46 MB) (new)


    First published: 08/07/2020

  • Document description

    • Annex I - List of the medicines affected by the referral
    • Annex II - Scientific conclusions of the CHMP or CMDh
    • Annex III - Changes to the summary of product characteristics, labelling or package leaflet - available when the CHMP or CMDh recommends changes to the product information. Also includes conditions for lifting of suspensions, if applicable
    • Annex IV - Conditions of the marketing authorisation - available when the CHMP or CMDh recommends other measures to be taken for the marketing authorisation such as safety measures or additional studies
    • Notification - A letter from a Member State, the European Commission or a marketing-authorisation holder requesting the initiation of a referral procedure
    • Rationale for triggering - Background provided by the party triggering the referral explaining the issues leading to the initiation of the procedure
    • PRAC list of questions - Questions agreed by the PRAC requesting further information to evaluate the issues identified
    • PRAC timetable - Timeframe agreed by the PRAC to receive information, assess the issues and adopt a recommendation
    • PRAC / CHMP or CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated


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