Regulatory Decision Summary for Tyruko (natalizumab)

The purpose of this new Drug Submission (NDS) is to seek market authorization of Tyruko as a biosimilar biologic drug to the reference biologic drug Tysabri (natalizumab for injection) for the treatment of relapsing-remitting form of multiple sclerosis (RRMS).

Tyruko (also called PB006 during the development program) is a proposed biosimilar to the Canadian reference biologic drug Tysabri (natalizumab for intravenous infusion) for the monotherapy treatment of adult patients with the relapsing-remitting form of multiple sclerosis (MS) on the basis of biosimilarity to the reference biologic drug. Pharmacokinetic similarity between Tyruko and the EU-sourced Tysabri, was supported by a pivotal Phase 1 comparative bioavailability study performed in healthy subjects in which the relative maximum observed serum concentration (C_max) and the 90% confidence interval [CI] for the area under the concentration-time curve to the last measurable concentration (AUC_T) met the Health Canada’s comparative bioavailability standards falling into the recommended comparative biosimilarity margin of 80% to 125%.

A supportive phase III efficacy and safety study between Tyruko and Tysabri was performed in adult patients with relapsing-remitting multiple sclerosis (RRMS). The safety profile of Tyruko appeared to be consistent with that of Tysabri. No patients in any treatment group experienced treatment-emergent adverse events leading to withdrawal from the study and no cases of Progressive Multifocal Leukoencephalopathy (PML) were reported, which is a known risk associated with natalizumab treatment. There were no deaths reported in the study and no new safety signals were identified from the Week 24 and Week 48 data.

There were no notable differences between Tyruko and EU-Tysabri regarding the immunogenicity profile and impact on exposure, efficacy and safety. Results from the four-week repeat-dose toxicity study in Cynomolgus monkeys also did not identify any noteworthy differences between the animals treated with Tyruko and EU-Tysabri.

Overall, in the clinical data package submitted, there were no areas where discrepancies between groups were of substantial magnitude or consistency to indicate clinically meaningful differences between both products.

The totality of evidence reviewed in the clinical assessment is supportive of biosimilarity between Tyruko and Tysabri; establishment of biosimilarity between Tyruko and Tysabri is contingent on the pivotal assessment of comparative physiochemical characteristics and functional properties. Please refer to the quality assessment for more information.

The Risk Management Plan (RMP) for Tyruko was reviewed by Health Canada and considered acceptable.

The Chemistry and Manufacturing information submitted for Tyruko has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

The labelling material met all applicable regulations and guidance.

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