Regulatory Decision Summary for Cibinqo

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:

New Drug Submission (New Active Substance)

Control number:

What was the purpose of this submission?

The purpose of this New Drug Submission (New Active Substance) was to seek marketing authorization for Cibinqo, an oral Janus kinase 1 (JAK1) inhibitor, for use in the treatment of refractory moderate to severe atopic dermatitis.

Why was the decision issued?

Cibinqo (abrocitinib) is a systemic JAK1 inhibitor that functions as a selective immunosuppressant. It is intended to be used in the treatment of patients with moderate to severe atopic dermatitis (AD) that is refractory to medicated topical treatment. 

The efficacy of Cibinqo was supported by data from three pivotal Phase 3 clinical studies, a Phase 2b study, two non-pivotal Phase 3 studies, and a Phase 3 long-term extension study. The co-primary endpoints of successful treatment response in the Investigator’s Global Assessment (IGA) and 75% reduction in the Eczema Area and Severity Index (EASI-75) were used to assess change in AD skin lesions after twelve weeks of treatment. Response rates for both the IGA and EASI-75 endpoints demonstrated a significant benefit in skin lesion improvement with both a 100 milligram (mg) and a 200 mg daily dosage in comparison to placebo. Though not formally tested statistically, the 200 mg daily dosage demonstrated an improved benefit relative to the 100 mg daily dosage. IGA response rates of up to 48.4% were observed in a combination therapy study, wherein patients remained on background medicated topical treatments. Similar results were seen with the EASI-75 endpoint, though overall response rates were higher (up to 70.3% in the combination therapy study). Key secondary endpoints used two different validated symptom scoring tools to provide evidence of pruritus relief. Demonstration of a more rapid onset of symptom relief relative to dupilumab, the only other systemic treatment approved for moderate to severe AD at the time of the study, was provided in the combination therapy study. The overall efficacy of Cibinqo was comparable (at 100 mg daily) or better (at 200 mg daily) relative to dupilumab over a twelve week treatment period. Sensitivity analyses and multiple other secondary endpoints supported the efficacy of both 100 mg and 200 mg daily dosages of Cibinqo. Patient-reported outcome assessments were consistent in indicating a significant quality of life benefit provided by Cibinqo relative to placebo.

While efficacious, there are significant safety concerns related to Cibinqo and to the drug class. JAK inhibitors can produce an increased risk of thrombosis, malignancies, and serious infections (as noted in the Serious Warnings and Precautions box in the proposed product monograph). Serious drug-related adverse events were not common in the submitted clinical studies and Cibinqo was generally well tolerated, with mostly mild adverse events experienced by some subjects. However, evidence of thrombosis came from observations of deep vein thrombosis and pulmonary embolism, which only occurred in subjects treated with the 200 mg daily dosage. Several cases of malignancies, all but one occurring in Cibinqo-treated subjects, were observed. The most commonly reported serious infections were herpes zoster, herpes simplex and pneumonia. Elderly subjects in particular are likely to have increased risk factors relevant to the serious side effects associated with Cibinqo, and showed dose-related increases in incidence of herpes zoster, thrombocytopenia, and lymphocytopenia. Recommendations to initiate elderly patients on the lower 100 mg daily dosage, and to step all patients down from the 200 mg daily dosage after achieving symptom control, were proposed to help mitigate risk of serious side effects. Though safety data from over 600 subjects administered Cibinqo over at least 48 weeks was summarized by the sponsor, there is significant uncertainty regarding long-term safety, including risk of malignancies and cardiovascular adverse reactions.

Recommended dosage adjustments were based on approximately two-fold increased exposures to the overall active moiety (unbound parent drug + active metabolites) in persons with moderate to severe renal impairment, or with the concomitant use of CYP2C19/2C9 inhibitors. In order to accommodate these dosage adjustment recommendations, a 50 mg tablet was developed for use in patients who would otherwise be prescribed the 100 mg dose. Quality and exposure data to support the use of all tablet strengths was found to be acceptable.

Severe AD can have a major impact on quality of life, and is associated with increased rates of anxiety, depression, and suicide. Patients with moderate to severe AD also have an increased risk of serious, potentially life-threatening, infections. Proposed dosing recommendations promote balancing the risks of the drug with its potential benefits. The revised indication proposed by Health Canada recommends using Cibinqo as a second-line systemic treatment, in recognition of the potentially life-threatening side effects associated with this drug. However, for patients who have had an inadequate response to prior treatments and continue to experience moderate to severe AD symptoms, and with appropriate risk mitigation, the potential benefits of Cibinqo outweigh the harms. 

Decision issued

Authorized; issued a Notice of Compliance (NOC) in accordance with the Food and Drug Regulations.