A Landmark Decision: Tenecteplase Gains FDA Approval
For decades, alteplase (Activase, tPA) was the only thrombolytic agent approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute ischemic stroke (AIS). However, on March 3, 2025, Genentech announced that the FDA had approved its drug TNKase (tenecteplase) for treating AIS in adults. This approval marked a significant shift in stroke care, making tenecteplase the second medication approved for this condition in nearly 30 years.
The approval was largely based on data from the AcT (Alteplase compared to Tenecteplase) clinical trial, a large, noninferiority study conducted across 22 stroke centers in Canada. The trial demonstrated that tenecteplase was comparable to alteplase in terms of both safety and efficacy for patients with AIS. This milestone followed years of growing off-label use, where tenecteplase was already favored in many stroke centers due to its practical advantages and strong clinical evidence.
The Shift from Off-Label Use to Official Guideline
Prior to its official approval, tenecteplase was widely used 'off-label' for AIS, a practice supported by a growing body of evidence and endorsements in national guidelines. The American Heart Association/American Stroke Association (AHA/ASA) had already updated its guidelines to recommend tenecteplase as a reasonable alternative to alteplase, particularly for patients eligible for mechanical thrombectomy. This institutional adoption was justified by clinical data demonstrating its safety and efficacy, which helped mitigate liability concerns associated with off-label use. The official FDA approval in March 2025 solidified its role and eliminated these concerns, paving the way for wider, standardized adoption.
Tenecteplase vs. Alteplase: A Detailed Comparison
Tenecteplase is a genetically modified variant of alteplase, engineered to have a longer half-life and greater specificity for fibrin, the main protein component of blood clots. These molecular differences translate into significant practical advantages in a time-critical emergency like a stroke.
Administration and Dosing
The most significant operational benefit of tenecteplase is its administration as a single intravenous (IV) bolus given over just five seconds. In contrast, alteplase requires an IV bolus followed by a 60-minute infusion. This simplified, rapid administration can reduce treatment delays and the potential for dosing errors, which is critical when every minute counts.
Efficacy and Safety
Multiple clinical trials have established that tenecteplase is non-inferior to alteplase in achieving excellent functional outcomes at 90 days. Studies like the EXTEND-IA TNK trial showed that tenecteplase may even be superior for patients with large vessel occlusions (LVO) who are also candidates for mechanical thrombectomy. In terms of safety, the rates of symptomatic intracranial hemorrhage (sICH), the most feared complication of thrombolysis, have been found to be similar between the two drugs across major trials. Some meta-analyses have even suggested lower mortality rates and major bleeding risks with tenecteplase.
Comparison Table: Tenecteplase (TNK) vs. Alteplase (tPA)
| Feature | Tenecteplase (TNKase) | Alteplase (Activase) |
|---|---|---|
| Administration | Single IV bolus over 5 seconds | IV bolus followed by a 60-minute infusion |
| FDA Approval for AIS | Yes, as of March 2025 | Yes |
| Fibrin Specificity | Higher | Lower |
| Half-Life | Longer | Shorter |
| Efficacy | Non-inferior to alteplase; may be superior for LVO | Established standard of care |
| Safety (sICH Risk) | Similar to alteplase | Established safety profile |
Landmark Clinical Trials Supporting Approval
The approval of tenecteplase was not based on a single study but on a culmination of evidence from numerous international trials.
- AcT Trial: This large Canadian trial was pivotal for the FDA's approval, confirming that tenecteplase (0.25 mg/kg) was non-inferior to alteplase for functional outcomes at 90 days in a broad population of stroke patients.
- EXTEND-IA TNK Trials: These trials focused on patients with large vessel occlusions eligible for mechanical thrombectomy. The results showed that tenecteplase improved reperfusion rates before the procedure compared to alteplase, supporting its use in this specific, high-risk group.
- TRACE-2 Trial: Conducted in China, this trial provided further robust evidence of tenecteplase's non-inferiority to alteplase, strengthening the case for a worldwide switch in thrombolytic agents.
- ATTEST-2 and NOR-TEST: These and other trials contributed to a large meta-analysis confirming tenecteplase's favorable safety and efficacy profile, including similar rates of mortality and sICH compared to alteplase.
Conclusion: A New Standard in Thrombolysis
The FDA's approval of tenecteplase for acute ischemic stroke in March 2025 marks a pivotal moment in stroke care. Backed by extensive clinical trial evidence and years of successful off-label use, tenecteplase is now officially recognized as a safe and effective alternative to alteplase. Its primary advantage lies in its simple and rapid single-bolus administration, which streamlines the treatment process in a critical emergency setting. While both drugs have similar safety profiles regarding intracranial hemorrhage, the operational benefits of tenecteplase have led many institutions and the AHA/ASA guidelines to favor it. This approval solidifies its position, not just as an alternative, but as the emerging new standard for thrombolysis in acute ischemic stroke.
For more detailed guidelines, consult the official recommendations from the American Heart Association/American Stroke Association.
