Multicentric, randomized, double-blind, comparative study in STEMI patients to establish clinical biosimilarity of biosimilar tenecteplase with reference product

Abstract

Objectives: Tenecteplase (TNK) is an established third-generation class 1A thrombolytic. The objective of the present study was to establish clinical biosimilarity of TNK biosimilar in a comparative phase III study with the reference product in the patients of ST elevation myocardial infarction (STEMI). Materials and Methods: In the double-blind, randomized, comparative clinical study 105 individuals were enrolled (70 in biosimilar TNK arm and 35 in the reference arm). Primary endpoint was thrombolysis in myocardial infarction (TIMI) 3-flow rate of the infarct-related artery at 90 min and all-cause mortality rate at 30 days' post dosing. Secondary endpoints considered were 50% resolution of elevated ST segment at 90 min, re-infarction till day 30, change in the left ventricular ejection fraction at day 30, events of ventricular tachyarrhythmias till day 30, and comparative pharmacokinetics. Immunogenicity was assessed along with the evaluation of safety at day 30. Results: TIMI grade 3-flow rate was achieved in 29 (43.28%) individuals in biosimilar arm and 14 (41.18%) individuals in the reference arm. The difference between the groups was statistically not significant (P = 0.8396). Four (5.71%) all-cause mortality were reported in biosimilar TNK arm compared to 2 (5.71%) in reference arm (all-cause mortality rate at 30 days' post dosing) and the difference between the two arms was statistically not significant (P = −1.00). Conclusion: Biosimilar TNK demonstrated biosimilar equivalence with the reference product in terms of the efficacy and safety analysis in this Phase III study and may be considered as a suitable alternative to reference TNK in patients with STEMI.