Summary Safety Review - Braftovi (encorafenib) - Assessing the Potential Risk of Severe Cutaneous Adverse Reactions

Braftovi (encorafenib)

Severe cutaneous adverse reactions (SCAR), a group of serious, potentially life-threatening, adverse reactions to drugs that involve the skin

• Health Canada’s review found a possible link between the use of Braftovi and the risk of SCAR.

• Health Canada has worked with the manufacturer to update the product safety information in the Canadian product monograph (CPM) for Braftovi to include the risk of SCAR. Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication.

Health Canada reviewed the potential risk of SCAR with the use of Braftovi. The safety review was triggered by safety information received from the manufacturer.

Braftovi belongs to a class of prescription drugs called B-Raf serine-threonine kinase (BRAF) inhibitors. Across all BRAF inhibitors marketed in Canada, Braftovi is the only one not labelled for SCAR.

This safety review focused on the following types of SCAR: Stevens-Johnson syndrome (SJS, a severe skin and mucous membrane disorder with peeling), toxic epidermal necrolysis (TEN, a more severe form of SJS), drug reaction with eosinophilia and systemic symptoms (DRESS, a severe reaction affecting the skin and internal organs), generalized bullous fixed drug eruption (GBFDE, a severe skin disorder with blisters), acute generalized exanthematous pustulosis (AGEP, a severe rash with pustules), and erythema multiforme (EM) major (a severe rash).

• Braftovi is a prescription drug authorized for sale in Canada for the treatment of:

  • Melanoma (a type of skin cancer), when used in combination with binimetinib. This type of skin cancer must have:

    • a mutation (change) in the BRAF gene, and

    • spread to other parts of the body or cannot be removed by surgery.

  • Metastatic (has spread to other parts of the body) colorectal cancer (a type of large intestine cancer), when used in combination with cetuximab. This type of intestine cancer must have:

    • a mutation in the BRAF gene, and

    • spread to other parts of the body and has already been treated with other cancer drugs.

• Since the completion of this review, Braftovi has also been authorized with conditions^a for the treatment of metastatic colorectal cancer with a mutation in the BRAF gene, when used in combination with cetuximab and mFOLFOX6 (chemotherapy). The risk of SCAR was not reviewed for this treatment indication.

• Braftovi has been marketed in Canada since 2021. It is currently available as 75 mg capsules.

• Since 2021, approximately 5,200 prescriptions for Braftovi have been dispensed by Canadian retail pharmacies. Overall, there has been a steady increase in prescriptions for Braftovi during this time.

• Health Canada reviewed the available information provided by the manufacturer, as well as from searches of the Canada Vigilance database^b and the scientific literature.

• At the time of the review, Health Canada had received 1 Canadian report of SCAR in a patient taking Braftovi. However, this case did not meet the criteria for further assessment to determine if there was a link due to incomplete information about when or how long the drug was taken relative to the adverse reaction.

• Health Canada reviewed 7 international cases of SCAR in patients taking Braftovi. Of the 7 cases, SJS and AGEP were reported in 1 case each in patients with colorectal cancer, and 1 case reported TEN, 3 reported DRESS, and 1 reported AGEP in patients with melanoma. All 7 cases were found to be possibly linked to the use of Braftovi and no deaths were reported. Most cases involved the combined use of Braftovi with another medication known to be linked to severe skin reactions.

• Health Canada’s review found a possible link between the use of Braftovi and the risk of SCAR.

• Health Canada has worked with the manufacturer to update the CPM for Braftovi to include the risk of SCAR.

• Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication.

• Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of Braftovi, and other health products, to the Canada Vigilance Program.

• Health Canada will continue to monitor safety information involving Braftovi, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified.

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

For additional information, contact the Marketed Health Products Directorate.

1. Authorized with conditions means it has passed Health Canada’s review, but the manufacturer has agreed to complete more studies to make sure the drug works the way it should.

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