Tenecteplase for Acute Ischemic Stroke: From Molecular Bioengineering to Phase III Pivotal Trials.
- 1Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
- 2Department of Radiology, Yonsei University College of Medicine, Seoul, Korea.
- 3Department of Neurology, Ajou University School of Medicine, Ajou University Medical Center, Suwon, Korea. [email protected].
Abstract
Intravenous thrombolysis with alteplase is a primary reperfusion therapy for acute ischemic stroke, yet its clinical utility is constrained by a short half-life, continuous infusion requirements, and susceptibility to plasminogen activator inhibitor-1. Tenecteplase, a bioengineered variant of alteplase, was developed to address these limitations through a prolonged half-life, increased fibrin specificity, and enhanced resistance to plasminogen activator inhibitor-1. These structural modifications enable single-bolus administration and reduce systemic fibrinolytic disturbance. In this review, we examine how the targeted molecular modifications of tenecteplase shaped its stepwise translational development in acute ischemic stroke. We first detail the limitations of alteplase, which motivated the transition to alternative agents, the molecular rationale for tenecteplase, and its preclinical evidence. Furthermore, we synthesize the phase II dose-finding trials that established 0.25 mg/kg as providing the optimal efficacy and safety balance, distinguishing it from the excess intracranial hemorrhage observed with the 0.4 mg/kg dose. Finally, we review the pivotal phase III trials across diverse populations demonstrating that tenecteplase 0.25 mg/kg is non-inferior to alteplase and represents a practical, evidence-based alternative, particularly where single-bolus administration may facilitate workflow or transfer for endovascular thrombectomy. Viewed through this molecular-to-clinical framework, the development of tenecteplase illustrates how targeted protein engineering can translate into pharmacological, operational, and clinical advantages in stroke reperfusion therapy.
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BibTeX
@article{jung2026tenecteplase,
title = {{Tenecteplase for Acute Ischemic Stroke: From Molecular Bioengineering to Phase III Pivotal Trials.}},
author = {Jae Wook Jung and Jin Soo Lee},
journal = {Journal of stroke},
year = {2026},
month = sep,
doi = {10.5853/jos.2026.03412},
url = {https://europepmc.org/article/MED/42894449},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Tenecteplase for Acute Ischemic Stroke: From Molecular Bioengineering to Phase III Pivotal Trials.
AU - Jae Wook Jung
AU - Jin Soo Lee
PY - 2026
DA - 2026/09/30
JO - Journal of stroke
DO - 10.5853/jos.2026.03412
UR - https://europepmc.org/article/MED/42894449
AB - Intravenous thrombolysis with alteplase is a primary reperfusion therapy for acute ischemic stroke, yet its clinical utility is constrained by a short half-life, continuous infusion requirements, and susceptibility to plasminogen activator inhibitor-1. Tenecteplase, a bioengineered variant of alteplase, was developed to address these limitations through a prolonged half-life, increased fibrin specificity, and enhanced resistance to plasminogen activator inhibitor-1. These structural modifications enable single-bolus administration and reduce systemic fibrinolytic disturbance. In this review, we examine how the targeted molecular modifications of tenecteplase shaped its stepwise translational development in acute ischemic stroke. We first detail the limitations of alteplase, which motivated the transition to alternative agents, the molecular rationale for tenecteplase, and its preclinical evidence. Furthermore, we synthesize the phase II dose-finding trials that established 0.25 mg/kg as providing the optimal efficacy and safety balance, distinguishing it from the excess intracranial hemorrhage observed with the 0.4 mg/kg dose. Finally, we review the pivotal phase III trials across diverse populations demonstrating that tenecteplase 0.25 mg/kg is non-inferior to alteplase and represents a practical, evidence-based alternative, particularly where single-bolus administration may facilitate workflow or transfer for endovascular thrombectomy. Viewed through this molecular-to-clinical framework, the development of tenecteplase illustrates how targeted protein engineering can translate into pharmacological, operational, and clinical advantages in stroke reperfusion therapy.
SN - 2287-6391
SN - 2287-6405
ER -