Regulatory Decision Summary for Otulfi / Otulfi IV

The purpose of this submission was to seek market authorization for Otulfi/Otulfi IV, a proposed biosimilar to the Canadian reference biologic product Stelara/Stelara IV (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. After evaluation of the submitted data package, Health Canada authorized indications in adult patients with plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis patients

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

Otulfi/Otulfi 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, and in adults with psoriatic arthritis, Crohn’s disease and ulcerative colitis.

Pharmacokinetic similarity between Otulfi and European Union (EU) licensed Stelara, the proxy to the Canadian reference biologic drug, was supported by a Phase 1 comparative bioavailability study conducted in healthy subjects in which the relative maximum (peak) concentration (C_max) and the 90% confidence interval for the area under the concentration versus time curve to the time of the last quantifiable concentration (AUC_last) were contained entirely within Health Canada’s prespecified comparative pharmacokinetic biosimilarity margin of 80.0% to 125.0%.

A supplemental phase 3 comparative efficacy and safety study did not detect clinically meaningful differences in efficacy or safety between Otulfi and EU-sourced Stelara in adult subjects with moderate-to-severe plaque psoriasis.

Across both clinical studies, anti-drug antibody (ADA) incidence was lower in subjects dosed with Otulfi compared with EU-licensed Stelara. ADA positive subjects had slightly lower exposures than ADA negative patients but that was not deemed clinically significant.

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 Otulfi/Otulfi IV is consistent with Stelara/Stelara IV and is favourable for all indications held by the reference biologic drug, with the exception of pediatric plaque psoriasis indication due to the lack of a subcutaneous vial presentation (required for dosing in these patients).

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

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

The chemistry and manufacturing information submitted for Otulfi/Otulfi 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 Otulfi (45 mg/0.5mL and 90 mg/mL) and Otulfi IV (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 Otulfi/Otulfi IV, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.