Regulatory Decision Summary for Steqeyma/Steqeyma IV

The purpose of this submission was to seek market authorization for Steqeyma/Steqeyma IV, a proposed biosimilar to the Canadian reference biologic product Stelara/Stelara IV (ustekinumab injection/ustekinumab for injection). The Sponsor sought the following indications held by the reference biologic drug, namely for the treatment of adult and pediatric (6-17 years of age) Plaque Psoriasis patients, as well as for the treatment of adult Psoriatic Arthritis, and Crohn’s Disease.

The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

Steqeyma/Steqeyma IV is a proposed biosimilar to the reference biologic drug Stelara/Stelara IV (ustekinumab injection/ustekinumab for injection).

In Canada, Stelara/Stelara IV was first approved in 2008 and is currently authorized for use in adults and pediatric patients between 6 – 17 years of age with Plaque Psoriasis (Ps), and in adults with Psoriatic Arthritis (PsA), Crohn’s Disease (CD) and Ulcerative Colitis (UC).

Following review, Steqeyma/Steqeyma I.V. is recommended for the treatment of adult plaque psoriasis, psoriatic arthritis, and Crohn’s disease indications.

This decision was based on the analysis of 3 studies (two pharmacokinetic studies and one confirmatory efficacy/safety study).

Pharmacokinetic similarity between Steqeyma and the reference biologic drug EU-sourced Stelara was supported by a Phase 1 comparative bioavailability study (Study CT-P43 1.2) conducted in healthy subjects in which the relative C_max and the 90% confidence interval for AUC_last were contained entirely within Health Canada’s prespecified comparative pharmacokinetic biosimilarity margin of 80.0% to 125.0%.

The comparative clinical efficacy and safety study (Study CT-P43 3.1) was designed to rule out any clinically meaningful difference between Steqeyma and Stelara. The study was a randomized, double-blind, active-controlled study in adult subjects with moderate to severe plaque psoriasis. 509 patients were randomized in a 1:1 ratio to either receive Steqeyma (n = 256) or Stelara (n = 253). The primary endpoint for efficacy evaluation was the mean percent improvement from baseline in PASI score at week 12.

At week 12, the primary efficacy analysis was conducted on patients that received the 45 mg dose of study drug. The results demonstrated an estimate of treatment difference of 0.94% (95% CI [-2.29,4.16]) for the difference between Steqeyma and Stelara as assessed by the PASI score from baseline. The difference was entirely contained within the predefined equivalence margin of -15% to 15%, thus supporting a demonstration of no clinically meaningful differences between Steqeyma and Stelara.

The safety profile of Steqeyma appears to be consistent with that of Stelara. Steqeyma was well-tolerated over 12 weeks and up to 52 weeks, with an incidence of adverse events (AEs) generally consistent with those observed for Stelara, with few serious AEs, AEs of special interest, or discontinuations due to AEs.

Across both clinical studies, anti-drug antibody (ADA) incidence was lower in subjects dosed with Steqeyma compared with EU-Stelara. Nevertheless, the impact of ADAs on efficacy and safety was consistent between patients dosed Steqeyma or EU-Stelara.

As a biosimilar to Stelara, Steqeyma has demonstrated a comparable benefit/risk profile for the treatment of adult plaque psoriasis, based on the evidence provided in this submission. Based on the scientific justification and the Sponsor’s rationale, this favourable profile is extended to the psoriatic arthritis and Crohn’s disease indications currently authorized for the Canadian reference product in line with relevant guidelines.

Overall, the totality of evidence reviewed in the clinical assessment is supportive of biosimilarity between Steqeyma and the reference biologic drug, Stelara; establishment of biosimilarity between Steqeyma and Stelara is contingent on the pivotal assessment of comparative physiochemical characteristics and functional properties.

An updated Risk Management Plan (RMP) for Steqeyma/Steqeyma IV was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for Steqeyma/Steqeyma IV 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 to be acceptable.

Overall, the benefit-harm-uncertainty profile was favourable for Steqeyma/Steqeyma IV (45 mg/0.5 mL, 90 mg/mL, 5 mg/mL) 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 Steqeyma/Steqeyma IV, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.