Regulatory Decision Summary for Elidel

Health Canada considers the changes proposed in this Supplemental New Drug Submission (SNDS) to be acceptable with respect to the safety and efficacy data submitted. The indication for Elidel was expanded to include pediatric patients 3 months to 2 years of age. This change was supported primarily by the safety and efficacy data from a 5-year, multicenter, multinational, open-label, active-controlled Phase 3 study CASM981C2306. This study was conducted in 2350 patients with mild to moderate atopic dermatitis (AD) that were randomized in a 1:1 ratio to either Elidel or the comparator treatment (first-line AD therapy). The overall efficacy results were similar in both treatment groups. At Week 3 and Week 6 of treatment (acute phase), overall Investigators Global Assessment (IGA) treatment success was achieved in more than 50% of patients in both treatment groups, and facial IGA treatment success was achieved in at least 61% of patients in both treatment groups. By the end of the fifth year of treatment, patients who remained in the trial still demonstrated treatment success. The total body surface area (TBSA) affected by AD decreased in both treatments groups in a similar degree throughout the study. The mean TBSA affected by AD at baseline was approximately 21% in both treatment groups, and it decreased to less than 10% by week 6 (acute phase); this response was sustained by the end of the fifth year of treatment in patients who remained in the trial. The overall incidence of adverse events (AEs), serious AEs, or discontinuations due to AEs were similar between the treatment groups. No malignancies were reported in the Elidel group.

The Serious Warnings and Precautions box regarding the safety of long-term use of topical calcineurin inhibitors and the risk of skin malignancies and lymphoma was removed from the Elidel Product Monograph. However, the information from the box warning was retained in the Warnings and Precautions section, under Carcinogenesis. This change was supported by safety data from above described clinical study CASM981C2306 and from study ASM981C2311 (the Pediatric Eczema Elective Registry; PEER). The PEER study is a prospective 10-year observational registry of pediatric subjects 2-17 years of age with AD who have used Elidel. Of the 8,014 enrolled subjects (3,729 male, 4,274 female), 3,373 have data up to 5 years and 1,842 have data up to 10 years. Over the 10-year duration, the use of Elidel has decreased relative to baseline; the proportions of subjects who reported using Elidel over the 6-month period prior to the 5-year and 10-year time points were 45% and 29%, respectively. The Data and Safety Monitoring Board of the PEER study has not reported any safety concerns. The results of the PEER registry do not indicate an increased risk of cancer at this time.

The overall benefit-risk for Elidel remains favorable when used under conditions described in the Elidel Product Monograph at this time.