Regulatory Decision Summary for Pyzchiva / Pyzchiva I.V. (ustekinumab)

The purpose of this submission was to seek market authorization for Pyzchiva / Pyzchiva I.V., a proposed biosimilar to the Canadian reference biologic drug 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, ulcerative colitis, and Crohn’s Disease.

Pyzchiva / Pyzchiva I.V. 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).

Pharmacokinetic similarity between Pyzchiva 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 (CI) 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 SB17-3001 was designed to rule out any clinically meaningful difference between Pyzchiva and Stelara. The study was a randomised, double-blind, active-controlled study in adult subjects with moderate to severe plaque psoriasis.

Subjects were randomised (1:1) to receive Pyzchiva (n = 232) or ustekinumab (n = 232). The primary efficacy endpoint was the Psoriasis Area and Severity Index (PASI) percent change (improvement) from baseline to week 12. The percent change from baseline in PASI at week 12 for Pyzchiva was compared to that for EU-Stelara and was found to be within the predefined equivalence margin to establish clinical comparability. Specifically, the adjusted difference in LSMeans at Week 12 was -0.6 (SE: 1.62) and the 95% CI of the adjusted treatment difference was (-3.780 to 2.579) which was entirely contained within the pre-defined equivalence margin of (-15%, 15%), thus supporting a demonstration of no clinically meaningful differences between Pyzchiva and Stelara.

The safety profile of Pyzchiva appears to be consistent with that of Stelara. Pyzchiva 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 Pyzchiva 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 Pyzchiva or EU-Stelara. No consistent impact of ADAs on safety was observed.

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

Health Canada has not authorized the pediatric plaque psoriasis indication because the Sponsor has not included a vial presentation within this submission.

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