Regulatory Decision Summary for Opzelura

The purpose of this Supplement to a New Drug Submission filed by Incyte Corporation was to obtain market authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for Opzelura (ruxolitinib [as phosphate]), 1.5% cream, to extend the indication to pediatric patients with atopic dermatitis ages 2 to 11 years of age.

Upon review of the submitted data package, Health Canada authorized Opzelura as filed.

The safety and efficacy of Opzelura was predominantly determined in a Phase 3 double-blind, randomized, vehicle-controlled trial (TRuE-AD3), which enrolled a total of 330 pediatric patients 2 to 11 years of age (51% of patients were 2 to 6 years of age and 49% of patients were 7 to 11 years of age). Females constituted 54% of patients, 55% of patients were White, 32% were Black, and 6% were Asian. Patients had affected body surface area (BSA) of 3% to 20%, and an Investigator Global Assessment (IGA) score of 2 (mild) to 3 (moderate) on a severity scale of 0 to 4. At baseline, patients had a mean affected BSA of 10.5%, 23.6% of patients had an IGA score of 2, and 76.4% of patients had a score of 3. Additionally, patients had a mean Eczema Area and Severity Index score of 8.6 (moderate) at baseline. For patients aged 6 to 11 years, the mean baseline itch numerical rating scale (NRS), defined as the 7-day average of the worst level of itch intensity in the last 24 hours, was 6.7 on a scale of 0 (no itch) to 10 (worst imaginable itch).

In the TRuE-AD3 study, patients were randomized 2:2:1 to treatment with Opzelura, ruxolitinib 0.75% cream, or vehicle cream twice daily for 8 weeks. Following the 8-week vehicle-controlled period, eligible patients entered the 44-week, long-term safety period in which patients treated areas of active or recurrent atopic dermatitis lesions as needed. Patients were instructed to stop treatment three days after clearance of lesions and restart treatment at the first signs of recurrence. Patients applying Opzelura or ruxolitinib 0.75% cream during the vehicle-controlled period continued the same treatment in the long-term safety period, whereas, those applying vehicle during the vehicle-controlled period were randomized 1:1 to Opzelura or ruxolitinib 0.75% cream during the long-term safety period.

The primary efficacy endpoint was the proportion of patients at week 8 achieving IGA treatment success (IGA-TS) defined as a score of 0 (clear) or 1 (almost clear) with a score of 2 or greater improvement from baseline.

The proportion of patients who achieved IGA-TS at week 8 in the TRuE-AD3 study was significantly higher in patients who applied Opzelura compared with patients who applied vehicle cream, 56.5% versus (vs) 10.8%, respectively.

During the long-term safety period, the proportion of patients with an IGA of 0 (clear) or 1 (almost clear) remained high at study visits during weeks 8 through 52 for patients in the Opzelura treatment group who continued the study and applied Opzelura on an intermittent, as needed basis. For patients who switched from vehicle to Opzelura, the proportion of patients with an IGA of 0 (clear) or 1 (almost clear) increased by week 12 (4 weeks after switching) and was maintained until the end of the 44-week long-term safety period with intermittent, as needed treatment with Opzelura.

With regard to safety, during the 8-week vehicle-controlled period, patients treated with Opzelura versus patients who applied the vehicle cream, the most common adverse reactions reported more with Opzelura were application site reaction (including application site pain, application site irritation, application site discomfort; 5% vs 0%), COVID-19 (4% vs 2%), pyrexia (2% vs 0%), and decreased white blood cell count (including leukopenia; 2% vs 0%). Adverse reactions such as upper respiratory tract infection and nasopharyngitis observed in patients 12 years of age and older were also observed in patients 2 to 11 years of age but at higher frequencies (9% vs 3% and 6% vs 2%, Opzelura vs vehicle cream, respectively). When compared with patients aged 12 years and older with atopic dermatitis, there were no meaningful differences in the safety profile of Opzelura in patients 2 to 11 years of age.

Uncertainties with Opzelura from a clinical perspective involve its long-term use due to the known class effects of JAK inhibitors, specifically the possibility of malignancies and major cardiovascular events, particularly in a vulnerable pediatric patient population. To mitigate these concerns and inform health care professionals the class effects of JAK inhibitors have been characterized in the Opzelura Product Monograph.

An updated Risk Management Plan for Opzelura was reviewed by Health Canada and considered acceptable.

The final labelling and Product Monograph were considered acceptable.

Overall, the benefit-harm-uncertainty profile of Opzelura is favourable for the authorized indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance was recommended.

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