Regulatory Decision Summary for Wynzora

The purpose of this New Drug Submission (NDS) was to obtain market authorization, pursuant to section C.08.004 of the Food and Drug Regulations for Wynzora, filed by MC2 therapeutics Ltd. This submission was filed for Wynzora (0.05 mg/g of calcipotriol, 0.5 mg/g of betamethasone (as dipropionate)) for the topical treatment of psoriasis vulgaris in adults for up to 8 weeks.

The proposed indication is supported by data from two multicenter, randomized, investigator-blind, parallel-group Phase 3 studies (MC2-01-C2 [C2]and MC2-01-C7 [C7]) conducted in adults with plaque psoriasis (psoriasis vulgaris) for at least 6 months. Both trials were vehicle- and active-comparator–controlled and employed a 3:1:3 randomization ratio to Wynzora (0.05mg/g of calcipotriol [CAL], 0.5 mg/g of betamethasone (as dipropionate [BDP]), vehicle, and active comparator (CAL/BDP gel in Study C7 and CAL/BDP suspension in Study C2). The studies were designed to demonstrate the superiority of Wynzora and the active comparator over vehicle and the non-inferiority of Wynzora to the active comparator.

In Study C2, 794 subjects were randomized (Wynzora: 342; active comparator: 337; vehicle: 115), and in Study C7, 490 subjects were randomized (Wynzora: 213; active comparator: 209; vehicle: 68). The study population included a range of skin types, which was representative of the general population of patients with plaque psoriasis. The trials enrolled subjects who had plaque psoriasis involving non-scalp regions (trunk and/or limbs), Physician Global Assessment (PGA) of mild or moderate disease, a modified Psoriasis Area and Severity Index (mPASI) score of ≥2 (Study C2) or ≥3 in (Study C7), and affected treatment area ranging from 2–30% of the of total body surface area (BSA). In Study C7, subjects with scalp psoriasis could be included, provided that the combined body and scalp involvement did not exceed 30% BSA. Most subjects had mild-to-moderate disease, while 20–35% had more extensive disease and 10–13% had more severe disease. Subjects applied study medication once daily for eight weeks.

Efficacy was evaluated using the PGA and mPASI. The PGA utilized a 5-point scale (clear, almost clear, mild, moderate, and severe) based on the average appearance of psoriatic lesions, while the mPASI was a composite score assessing disease severity (erythema, scaling, and induration) and the extent of affected area, excluding the scalp, face, and flexures. The primary efficacy endpoint in Study C2 was the proportion of subjects achieving treatment success at Week 8, defined as a ≥2-point improvement in PGA. This endpoint served as a secondary endpoint in Study C7, where the primary endpoint was the percentage change in mPASI on the body from Baseline to Week 8 – the same measure that served as the secondary endpoint in Study C2.

The primary efficacy endpoints were achieved in both studies. At Week 8, Wynzora was statistically superior to vehicle in achieving treatment success (PGA) (p <0.0001) (Wynzora: 37.4% and 50.7% in Study C2 and C7, respectively; active comparator: 22.8% and 42.7%, respectively; vehicle: 3.7% and 6.1%, respectively). Wynzora was statistically superior to vehicle in reducing mPASI from baseline at Week 8 (p <0.0001) (Wynzora: 65.7% and 62.9% in Study C2 and C7, respectively; active comparator: 63.5% and 51.3%, respectively; vehicle: 11.7% and 22.9%, respectively). Both studies also demonstrated the non-inferiority of Wynzora to the active comparator.

The efficacy of Wynzora was further supported by the study’s key multiplicity controlled secondary endpoints, including the change in itch intensity, evaluated using the numerical rating scale (NRS) for itch from baseline to Week 4 in Study C2, and PGA treatment success on the scalp at Week 8 in Study C7. Among subjects with a baseline peak pruritus NRS score ≥4, 60.2% of those treated with Wynzora achieved a ≥4-point improvement, compared with 21.4% in the vehicle group at Week 4. Scalp PGA success rates were also significantly higher for Wynzora than for vehicle at Week 4 (p = 0.0051) and Week 8 (p = 0.0002).

The safety review was based on the integrated safety database from two Phase 3 trials in patients with plaque psoriasis, supported by data from targeted Phase 2 studies evaluating hypothalamic–pituitary–adrenal (HPA) axis function, systemic exposure, and local tolerability. The pooled Phase 3 safety dataset included 1,283 subjects, of whom 555 subjects applied Wynzora (213 in C7 and 342 in C2) for up to 8 weeks. The incidence of treatment-emergent-adverse events (TEAEs), and serious adverse events (SAEs) was similar across treatment groups, and most adverse reactions occurred at frequencies below 1%. The most common adverse reaction was application-site pain (1.1 %) in adults treated with Wynzora for up to 8 weeks. Less common (<1 %) reactions included application site- folliculitis,- irritation, -pruritus, -eczema, exfoliation, and -telangiectasia, insomnia, pruritus, rash, and urticaria.

There were no treatment-related SAEs or clinically significant class-related safety findings, including effects on calcium metabolism. No notable HPA-axis suppression, a known effect of topical corticosteroids, was observed under maximal-use conditions in adults and adolescents for up to 8 weeks. In phototoxicity studies, Wynzora did not show potential for phototoxicity or photosensitization. All adverse events are adequately captured in the Wynzora Product Monograph.

The chemistry and manufacturing information submitted for Wynzora (0.05 mg/g CAL and 0.5 mg BDP) has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and Product Monograph were considered acceptable.

Overall, the benefit-harm-uncertainty profile was favourable for Wynzora (0.05 mg/g CAL and 0.5 mg/g BDP) for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

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