Regulatory Decision Summary for Eucrisa

Review decision

The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.

Product type:


Medicinal ingredient(s):


Therapeutic area:

Other Dermatological Preparations

Type of submission:

Supplemental New Drug Submission (SNDS)

Control number:

What was the purpose of this submission?


This Supplemental New Drug Submission (SNDS) was filed to change the minimum authorized age for the use of Eucrisa from 2 years of age to 3 months of age, for the treatment of atopic dermatitis (AD).


Why was the decision issued?


One single-arm clinical study was conducted by the sponsor to support the efficacy and safety of Eucrisa, a 2% crisaborole cream, in treating atopic dermatitis (AD) in children 3 months to less than 2 years of age. Crisaborole is a selective phosphodiesterase-4 inhibitor with anti-inflammatory properties. The use of several types of anti-inflammatory creams, including crisaborole-containing cream, have previously demonstrated efficacy in treating AD. The primary endpoint of the study provided for this submission was safety, assessed mainly by the incidence of treatment-emergent adverse events. Pharmacokinetic measurements of crisaborole and its major metabolites, as well as efficacy endpoints, were considered as exploratory. Extrapolation of efficacy from results obtained in older children with AD was used to support the overall benefit of Eucrisa in children 3 months to less than 2 years of age.

The main efficacy endpoint used in the study was success in the investigator’s static global assessment (ISGA) at Day 28. This endpoint was the same as that used for the previously conducted pivotal phase 3 trials that included subjects 2 years of age or older. The ISGA is a 5-point symptom scoring system, with success being counted as a decrease of at least 2 points. There was a similarity in the numbers achieving success at Day 28 in subjects less than 2 years of age (30.2%) and subjects 2 years of age or older (32.1%). Though supportive of efficacy, the lack of a control arm limited conclusions that could be drawn from this study. Thus, a rationale for extrapolation of efficacy from results obtained in older subjects was also provided by the sponsor.

Extrapolation of efficacy from patients 2 years of age or older was justified by the following: 1) Itchy, inflamed skin is common to AD in all age groups, though the pattern and distribution of skin lesions typically differs between children less than 2 years of age, children 2 to 12 years of age, and adolescents/adults. 2) The underlying pathophysiology is thought to be highly similar across these 3 age groups. Pruritus commonly results in scratching and an amplification of inflammation in the skin. 3) The skin is anatomically mature at birth, though some change, such as a thickening of the stratum corneum, occurs with maturation. 4) Irrespective of age, it is thought that optimal control of AD is achieved through skin hydration, restoration of the skin barrier, and the control of skin inflammation. The results obtained for children 3 months to less than 2 years of age were consistent with the likelihood that Eucrisa will be of benefit in this regard.

Pharmacokinetic analysis in the infants and toddlers indicated some potential for increased exposure to crisaborole relative to older patients, though there was uncertainty in the data collected due to outlier values. Excluding values assessed as likely having been obtained due to methodological error, exposures were similar (similar overall systemic exposure, with maximum plasma concentration increased by 1.25x) between AD patients 3 month to less than 2 years of age compared to patients 2 to 17 years of age. No patients with higher recorded exposure values experienced any unique adverse events. No safety results were indicative of toxicity associated with higher drug exposure.

Treatment-emergent adverse events were consistent with adverse events previously reported for patients 2 years of age or above. The only treatment-related adverse events that occurred in clinical trials across all age groups were application site pain/discomfort (localized burning and stinging) and erythema. Other treatment-emergent adverse events that occurred in children 3 months to less than 2 years of age included upper respiratory tract infections and skin infections. Similar occurrence of these adverse events in subjects over 2 years of age was not judged to be treatment-related. No serious adverse events were judged to be related to the use of Eucrisa. No other safety parameters, including vital signs, laboratory values, and height and weight measurements demonstrated any clinically meaningful changes with the use of Eucrisa.

Overall, the benefit-harm-uncertainty profile for Eucrisa in the treatment of AD was considered favourable for its use in children 3 months to less than 2 years of age


Decision issued

Authorized; issued a Notice of Compliance in accordance with the Food and Drug Regulations