Regulatory Decision Summary for Wezlana/Wezlana I.V.

The purpose of this submission was to seek market authorization for Wezlana/Wezlana I.V., a proposed biosimilar to the Canadian reference biologic product Stelara/Stelara I.V. (ustekinumab injection/ustekinumab for injection). The Sponsor sought all the 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, Crohn’s Disease and Ulcerative Colitis patients.

Wezlana/Wezlana I.V. is a proposed biosimilar to the reference biologic drug Stelara/Stelara I.V. (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).

Pharmacokinetic similarity between Wezlana and the reference biologic drug EU-sourced Stelara was supported by a Phase 1 comparative bioavailability study 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 20190232) was designed to rule out any clinically meaningful difference between Wezlana and Stelara. The study was a randomized, double-blind, active-controlled study in adult subjects with moderate to severe plaque psoriasis. Subjects were randomized (1:1) to receive Wezlana (n = 281) or Stelara (n = 282). The primary efficacy endpoint was the Psoriasis Area and Severity Index (PASI) percent change (improvement) from baseline to week 12.

The mean (SD) PASI percent change (improvement) from baseline to week 12 based on multiple imputation was 81.46 (20.058) and 81.45 (20.004). The point estimate of the difference between means in PASI percent change (improvement) from baseline to week 12 between the treatment groups was 0.14 with a 2-sided 95% CI of (-3.16, 3.43). The 95% CI was within the prespecified similarity margin of (-10, +10), thus supporting a demonstration of no clinically meaningful differences between Wezlana and ustekinumab. Additional secondary efficacy endpoints were suggestive of similarly; however, these endpoints were not assessed with the same rigor as the primary efficacy endpoint.

The safety profile of Wezlana appears to be consistent with that of Stelara. Wezlana 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 Wezlana compared with EU-Stelara. ADA positive subjects had lower exposures than ADA negative patients and a small but not clinically meaningful decrease in efficacy was observed in ADA positive vs ADA negative patients. The impact of ADAs on exposure and efficacy was consistent between patients dosed with Wezlana or EU-Stelara. No consistent impact of ADAs on safety was observed.

There were no areas where discrepancies between groups were of substantial magnitude or consistency to indicate clinically meaningful differences between products. As such, the benefit-risk profile of Wezlana is consistent with Stelara and is favourable for all indications held by the reference biologic drug.

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