Regulatory Decision Summary for Tyenne

The purpose of this new drug submission (NDS) was to seek market authorization of the biosimilar biologic drug, Tyenne (tocilizumab), for use in the treatment of rheumatoid arthritis (RA); systemic juvenile idiopathic arthritis (SJIA) in patients 1 year subcutaneous route (SC)/2 years of age and older intravenous route (IV); juvenile idiopathic polyarthritis (PJIA) in patients 2 years of age and older; giant cell arteritis (GCA), chimeric antigen receptor (CAR)-T cell-induced severe or life-threatening CRS in adults and pediatric patients 2 years of age and older; and coronavirus disease 2019 (COVID-19) in hospitalized adults who are receiving systemic corticosteroids and require supplemental oxygen or mechanical ventilation.

Tyenne is a biosimilar to the Canadian reference product Actemra (tocilizumab). In Canada, Actemra was approved in 2010 and is currently indicated for the treatment of rheumatoid arthritis (RA); systemic juvenile idiopathic arthritis (SJIA) in patients 1 year (SC route)/2 years of age and older (IV route); juvenile idiopathic polyarthritis (PJIA) in patients 2 years of age and older; giant cell arteritis (GCA); chimeric antigen receptor (CAR)-T cell-induced severe or life-threatening CRS in adults and pediatric patients 2 years of age and older; and COVID-19 in hospitalized adults who are receiving systemic corticosteroids and require supplemental oxygen or mechanical ventilation. Tyenne is the first Actemra biosimilar sought for market authorization in Canada.

Pharmacokinetic similarity between Tyenne and Actemra was supported by two phase 1 similarity studies both conducted in healthy subjects in which the 90% confidence interval for the relative C_max and AUC_last were contained entirely within Health Canada’s prespecified comparative pharmacokinetic biosimilarity margin of 80.0% to 125.0%.

The safety profile of Tyenne was consistent with that of Actemra in a phase 3 comparative clinical efficacy and safety study. Tyenne was well tolerated over 55 weeks and up to 63 weeks, with an incidence of adverse events (AEs) generally consistent with those observed for Actemra. Robust conclusions regarding the safety profile of Tyenne are limited by the relatively small number of patients included in the study.

The overall assessment is based on the totality of evidence including analytical, nonclinical and clinical data showing consistency with the mechanism of action and signaling known for tocilizumab, similar efficacy, PK, immunogenicity and safety profiles. The totality of evidence supports biosimilarity between Tyenne and the Canadian reference biologic product, Actemra. There were no areas where discrepancies between groups that were of substantial magnitude or consistency to indicate clinically meaningful differences between products. Given the established favorable benefit-risk profile of Actemra in all its approved indications and the totality-of-the-evidence, supporting the biosimilarity of Tyenne to Actemra, the benefit-risk profile for Tyenne is deemed consistent with Actemra and is therefore favorable in all the sought indications for which Actemra is currently authorized.

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