FDA Approves Tenecteplase (TNKase) for Acute Ischemic Stroke

The US Food and Drug Administration (FDA) has approved tenecteplase (TNKase) for the treatment of adults with acute ischemic stroke (AIS), becoming the first stroke medicine approved by the regulatory agency in nearly 3 decades.1

Announced by Genentech, on March 3, 2025, tenecteplase, a tissue plasminogen activator, clot-dissolving, thrombolytic medicine, is administered as a single, five-second intravenous (IV) bolus. The company announced further plans to introduce a 25 mg vial configuration in the coming months to support its approval for AIS.

“Today’s approval is a significant step forward and underscores our commitment to advancing stroke treatment options for patients,” said Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech.1 “[Tenecteplase] provides a faster and simpler administration, which can be critical for anyone who is dealing with an acute stroke.”

The fifth leading cause of death, and the leading cause of long-term disability in the US, more than 795,000 people are impacted by stroke each year. Approximately one-quarter of these events occur among individuals with a prior history of strokes. Brain damage can progress suddenly during AIS, making early intervention crucial to prevent irreversible loss of nervous tissue.2

Tenecteplase’s approval for AIS was awarded based on the large, multicenter, non-inferiority Phase 3 AcT trial comparing the drug to the standard-of-care AIS treatment, alteplase (Activase). Results from AcT revealed the noninferiority of tenecteplase to alteplase for safety and efficacy in AIS treatment.1

Approximately 1600 patients with AIS were enrolled from 22 primary and comprehensive stroke sites in Canada and randomly assigned to intravenous tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg as a bolus and then a 60-minute infusion of the remaining 0.81 mg/kg. The trial’s primary outcome was the number of patients who achieved a modified Rankin Scale (mRS) score of 0–1 at 90–120 days after treatment.3

At the data cutoff, 296 (36.9%) of 802 patients in the tenecteplase cohort and 266 (34.8%) of 765 in the alteplase cohort achieved an mRs score of 0–1 at the 90–120 window, meeting the prespecified non-inferiority threshold of ≥–5% (unadjusted risk difference, 2.1% [95% CI, –2.6 to 6.9]).

Safety findings reported 3.4% (27 of 800) and 3.2% (24 of 763) of patients in the tenecteplase and alteplase-treated cohorts, respectively, experienced 24-hour symptomatic intracerebral hemorrhage (ICH). Within 90 days of initiating treatment, 15.3% (122 of 796) and 15.4% (117 of 763) of patients died in both groups, respectively.

Genentech reported the most frequent adverse reactions associated with tenecteplase are bleeding and hypersensitivity. The Dosage and Administration section of the label recommends treatment initiation immediately or within 3 hours after the onset of stroke symptoms.1

Approval of tenecteplase marks Genentech’s second approval for stroke and only the second approval for AIS after the 2015 approval of alteplase. With the single five-second IV bolus, tenecteplase offers a faster and simpler administration than the standard-of-care. The FDA previously approved tenecteplase to treat acute ST-elevation myocardial infarction (STEMI) in adults.1

References

1. FDA Approves Genentech’s TNKase® in Acute Ischemic Stroke in Adults. News release. Genentech. March 3, 2025. Accessed March 3, 2025. https://www.gene.com/media/press-releases/15053/2025-03-03/fda-approves-genentechs-tnkase-in-acute-

2. Hui C, Tadi P, Khan Suheb MZ, et al. Ischemic Stroke. [Updated 2024 Apr 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499997/

3. Menon BK, Buck BH, Singh N, et al. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. Lancet. 2022;400(10347):161-169. doi:10.1016/S0140-6736(22)01054-6