Who Owns TNKase?

Tenecteplase was developed by Genentech scientists in the 1990s as a modified version of alteplase (Activase), the company's first-generation recombinant tissue plasminogen activator. The goal was to engineer a molecule with a longer plasma half-life, higher fibrin specificity, and greater resistance to plasminogen activator inhibitor-1. These properties would allow administration as a single intravenous bolus rather than the prolonged infusion required for alteplase.

The key modifications to the alteplase molecule included three amino acid substitutions and a carbohydrate modification at one of the glycosylation sites. The result was a protein with an initial plasma half-life of 20 to 24 minutes, compared with approximately 5 minutes for alteplase. The terminal phase half-life of tenecteplase is 90 to 130 minutes. The increased fibrin specificity means the drug preferentially activates plasminogen at the clot surface rather than in the general circulation, potentially reducing systemic bleeding risk.

The FDA approved TNKase on June 2, 2000 for the reduction of mortality associated with acute myocardial infarction. The approval was based on the ASSENT-2 trial, a large multicenter study of nearly 17,000 patients that compared weight-adjusted tenecteplase given as a single bolus against the standard 90-minute accelerated infusion of alteplase. The trial found that 30-day mortality rates were virtually equivalent between the two treatments, with lower rates of non-cerebral bleeding in the tenecteplase group. The weight-tiered dosing regimen ranged from 30 to 50 mg based on patient body weight.

For the first 25 years of its market life, TNKase was approved only for acute myocardial infarction. Its use in ischemic stroke was off-label, though clinical interest grew as researchers recognized the practical advantages of single-bolus administration in emergency stroke care. Multiple randomized trials compared tenecteplase against alteplase for acute ischemic stroke, including the NOR-TEST, TAA-I, and most notably the AcT (Alteplase compared to Tenecteplase) trial conducted by the University of Calgary.

The AcT trial enrolled approximately 1,600 patients across 22 Canadian stroke centers and was funded by the Canadian Institutes of Health Research. It demonstrated that tenecteplase at a dose of 0.25 mg per kilogram was non-inferior to alteplase at the standard 0.9 mg per kilogram dose in terms of functional outcomes at 90 days. The results were published in The Lancet Neurology and formed the basis for the FDA stroke indication.

On March 3, 2025, the FDA approved TNKase for the treatment of acute ischemic stroke in adults. This was the first new drug approval for acute ischemic stroke in nearly 30 years, since Activase (alteplase) received its stroke indication in 1996. Genentech introduced a new 25 mg vial configuration to support the stroke indication, as the weight-based dosing for stroke (0.25 mg per kilogram, maximum 25 mg) differs from the higher doses used for myocardial infarction.

The 2026 AHA/ASA Guideline for the Early Management of Patients With Acute Ischemic Stroke, published in January 2026, gave a Class 1 recommendation for either tenecteplase or alteplase within 4.5 hours of symptom onset. The guideline noted that tenecteplase may offer practical advantages over alteplase due to its single-bolus administration and fewer dosing complexities. This represented a shift from prior guidelines that primarily endorsed alteplase with tenecteplase as an alternative.

In 2026, Genentech announced the commercial discontinuation of Activase (alteplase) 100 mg vials and kits in the United States, effective August 28, 2026. This made TNKase the primary Genentech thrombolytic available for acute ischemic stroke in the U.S. market. The discontinuation reflected the clinical community's shift toward tenecteplase, driven by its ease of administration and the 2025 FDA stroke approval.