Platform Presentation The Joint Annual Meeting of the Stroke Society of Australasia (SSA) and Smartstrokes 2023

Biochemical and Enzymatic Comparison of Metalyse (Tenecteplase) and Generic rh-TNK-tPA (#79)

Isabel Tippett 1 , Zikou Liu 1 , Amy McDonald 2 , Andrew Bivard 2 , Longting Lin 3 , Bruce C Campbell 2 , Mark Parsons 4 5 , Robert Medcalf 1
  1. Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia
  2. Neurology, Royal Melbourne Hospital, Parkville, VIC, Australia
  3. Sydney Brain Center, South West Sydney Clinical Campuses, Sydney, NSW, Australia
  4. Department of Neurology, Liverpool Hospital UNSW South Western Sydney, Sydney, NSW, Australia
  5. Ingham Institute for Applied Medical Research, Sydney, NSW, Australia

Background: Tenecteplase (TNK) is a variant of tissue-type plasminogen activator (tPA; “alteplase”) that differs at only 6 amino acids. TNK has a longer plasma half-life than tPA and clinical studies have indicated that TNK is non-inferior to tPA as a thrombolytic for patients with acute ischaemic stroke (AIS). TNK, like tPA exists in a single chain (intact) form and as a two-chain form after cleavage by plasmin although both forms are catalytically active. A generic form of TNK (rhTNK-tPA) has been compared against alteplase in Chinese patients with AIS and was found to be non-inferior1. However, direct comparison of generic rhTNK-tPA with TNK has not been undertaken.

Aims: To undertake a biochemical and enzymatic comparison of TNK with generic rhTNK-tPA.

Methods: Generic rhTNK-tPA was provided by the China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou) Co. Ltd. The company had no role in this study. Tenecteplase was obtained from Victorian hospitals remaining after thrombolysis for patients with AIS. Equimolar concentration of TNK and rhTNK-tPA were compared for fibrinolytic and plasminogen activating capacity by fibrin zymography and amidolytic assays, respectively. The protein constituents of each formulation were compared by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) and Coomassie staining under reduced and non-reduced conditions.

Results: Fibrin zymographic analysis revealed that both forms of TNK possessed fibrinolytic activity that migrated at the same molecular weight and had similar dose-dependent activity. Similarly, the amidolytic activity of each formulation did not significantly vary. Coomassie staining after SDS-PAGE under non-reduced conditions showed the identical pattern for both formulations. However, under reduced conditions, rhTNK-tPA appeared to be more homogeneous having a greater percentage of single-chain v two-chain-rhTNK-tPA compared to tenecteplase.

Conclusion: TNK and rhTNK-tPA are essentially indistinguishable in relation to fibrinolytic and plasminogen activating capacity.

  1. Wang et al. (2023) Lancet 401(10377) 645-654