Regulatory Decision Summary for Metvix

This Supplement to a New Drug Submission (SNDS) was filed to update the wording in the Indications and Dosage and Administration sections of the Product Monograph (PM) for Metvix to clarify its appropriateness for first-line treatment of actinic keratosis (AK) and to specify modalities for treating affected areas of skin. Additionally, the sponsor proposed the inclusion of the adverse event transient global amnesia (TGA) in the Warnings and Precautions section. Format changes were also incorporated in accordance with Health Canada’s Guidance Document: Product Monograph (2020).

The efficacy of Metvix photodynamic therapy (METVIX-PDT) for the treatment of actinic keratosis (AK) was demonstrated in two Phase III, multicentre, double-blind, randomized, vehicle-controlled, parallel-group trials (PC T404/05 and PC T405/05). These trials included patients with multiple, untreated, non-pigmented, non-hyperkeratotic AK lesions on the face and/or scalp for whom other standard therapies (e.g., surgery or cryotherapy at that time) were considered medically less appropriate. Since its approval in 2009, several studies have evaluated the efficacy of Metvix as a first-line alternative, particularly for multiple lesions (field-directed treatment), with no notable safety concerns.

In this submission, the sponsor proposed to remove the statement “when other therapies are considered less appropriate” from the AK indication and to add the term “and/or field cancerization” to the Dosage and Administration section of the Product Monograph (PM). The intent was to clarify that Metvix-PDT can be used not only to treat single isolated lesions but also multiple lesions or areas of field cancerization. Based on the evidence provided, the Pharmaceutical Drugs Directorate (PDD) agreed with the sponsor that the statement should be removed. The final recommended AK indication is:

“Metvix topical cream in combination with 630 nm wavelength red light illumination using the Aktilite CL 128 lamp (conventional photodynamic therapy [c-PDT]) or in combination with daylight (daylight photodynamic therapy [DL-PDT]) is indicated for the treatment of thin or non-hyperkeratotic and non-pigmented actinic keratosis on the face and scalp.”

The sponsor also proposed the addition of the term “and/or field cancerization” to the Dosage and Administration section to clarify that Metvix-PDT can be used for multiple lesions. This change was supported by evidence from a pharmacokinetic study and published literature. While PDD agreed with the sponsor on the importance of clarifying administration modalities, the term “field cancerization” was considered imprecise due to the lack of a standard definition. To avoid vague terminology in the PM, PDD recommended replacing “field cancerization” with “field-directed treatment,” which was accepted by the sponsor.

The association between transient global amnesia (TGA) and Metvix-c-PDT has been known since 2017, with no increase in frequency or severity of reports over the past five years. PDD agreed with the sponsor to include TGA in the PM to raise awareness and align safety information across the PM, the Company Core Data Sheet (CCDS), and the PMs of similar products.

In summary, PDD considers that the PM changes proposed in this SNDS do not affect the way in which the product is used, but rather provide clarification on the appropriateness of using Metvix as a first-line alternative for both single and multiple AK lesions. This aligns with well-established and widely recommended clinical practice.

Based on the evidence reviewed, the benefit-risk profile of Metvix remains favourable.

For further details about Metvix, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.