Summary Safety Review - Picato (ingenol mebutate) - Assessing the Potential Risk of Skin Cancer

Review decision

A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.


Issued: 2020-07-02

Product

Picato (ingenol mebutate)

Potential Safety Issue

Skin cancer

Key Messages

  • Picato (ingenol mebutate) is a prescription drug authorized for sale in Canada for use on the skin (topically) in adults to treat actinic keratosis (AK), a condition where thick, hard and scaly patches appear on skin caused by too much exposure to the sun (UV exposure).
  • Health Canada reviewed the risk of skin cancer with Picato based on new safety information from international clinical trials that found an increased risk of skin cancer in patients treated with this drug.
  • Health Canada's review concluded that there may be a link between Picato and the risk of skin cancer.
  • Health Canada will ask for additional information from the manufacturer to determine whether Picato continues to be an effective and safe treatment option for actinic keratosis (AK).

Overview

Health Canada reviewed the potential risk of skin cancer with the use of Picato. The review was triggered by new safety information from international clinical trials that found an increased risk of skin cancer in patients treated with Picato.

Use in Canada

  • Picato (ingenol mebutate) is a prescription drug authorized for sale in Canada for topical use in adults to treat actinic keratosis (AK), a condition where thick, hard, and scaly patches appear on skin that has been damaged by too much sun (UV) exposure.
  • Ingenol mebutate has been marketed in Canada since 2013 under the brand name Picato. Picato is a gel for use on the skin (topically) available in 2 strengths, 0.015% and 0.05%.
  • There were about 5,000 prescriptions filled for Picato in Canada in 2019.

Safety Review Findings

  • Health Canada reviewed the available information from searches of the Canada Vigilance databasea, evidence given by the manufacturer, and studies published in scientific and medical literature.
  • Health Canada's review focused on 43 international clinical trials and found that there was enough evidence to link the use of Picato with skin cancer.
  • Health Canada reviewed 29 case reports (including one Canadian case ) of skin cancer in patients treated with Picato. Of the 29 cases, 26 cases were found to be possibly linked. In the other 3 cases (including the Canadian case), a link was found to be unlikely because of the presence of the skin cancer inside and outside of the area treated with the drug. Assessing whether the skin cancer was related to the use of Picato was challenging in all 29 cases due to several factors including a medical history of skin cancer or use of other medications known to increase the risk of skin cancer.
  • Health Canada assessed 12 studies published in scientific and medical literature in order to determine the link between the use of Picato and skin cancer. Health Canada's review found that 6 of the 12 studies had evidence of skin cancer with the use of Picato.
  • The European Medicines Agency (EMA) has also reviewed this safety issue. In April 2020, it concluded that Picato may increase the risk of skin cancer and that its risks outweigh its benefits. On February 11, 2020, the manufacturer voluntarily withdrew the product from the European market.
  • Picato is currently authorized for sale in other countries including the United States of America, Australia, and New Zealand.

Conclusions and actions

  • Health Canada's review found that there may be a link between Picato and the risk of skin cancer.
  • Health Canada will ask for additional information from the manufacturer to determine whether the benefits of the use of Picato continue to outweigh its risks as a treatment option for AK.
  • Health Canada will continue to monitor safety information involving Picato to identify and assess potential risks, as it does for all health products on the Canadian market. Health Canada will take appropriate and timely action if and when new health risks are identified.

Additional information

The analysis that contributed to this safety review included information from clinical trials, Canadian and international case reports, scientific and medical literature, and what is known about the use of this drug both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

Footnotes

  1. Canadian reports can be accessed through the Canada Vigilance Online Database.