FDA Approves Tenecteplase for Acute Ischemic Stroke

Levi Garraway, MD, PhD

(Credit: Genentech)

The FDA has approved tenecteplase (TNKase; Genentech) for the treatment of acute ischemic stroke (AIS) in adults, according to a Genentech announcement.¹ The thrombolytic medicine is an intravenous (IV) tissue plasminogen activator that is clot-dissolving, administered as a single 5-second IV bolus. The company noted that it will be providing a 25-mg vial configuration in the coming months to support the approval.

Tenecteplase’s approval was based on the data collected from the phase 3 AcT trial (NCT03889249), which enrolled 1600 patients and compared outcomes between patients treated with the new therapy compared with alteplase. The data showed that 36.9% of those treated with tenecteplase (296 of 802) reported modified Rankin Scores (mRS) of 0-1 in the 90- to 120-day window compared with 34.8% of the alteplase group (266 of 765), showing noninferiority and an unadjusted risk difference of 2.1% (95% CI, –2.6 to 6.9).²

The safety analyses revealed that 3.4% of patients (27 of 800) in the tenecteplase-treated group and 3.2% of patients (24 of 763) in the alteplase-treated group had 24-hour symptomatic intracerebral hemorrhage (ICH). Additionally, 15.3% (122 of 796) and 15.4% (117 of 763) of patients died within 90 days of starting treatment in both groups, respectively.²

“Today’s approval is a significant step forward and underscores our commitment to advancing stroke treatment options for patients. TNKase provides a faster and simpler administration, which can be critical for anyone who is dealing with an acute stroke,” Levi Garraway, MD, PhD, the chief medical officer and head of Global Product Development at Genentech, said in a statement.¹

An analysis from the AcT trial published in 2023 in Stroke suggested that the faster administration of tenecteplase resulted in better clinical outcomes compared with alteplase. Those data revealed that the type of thrombolytic agent (tenecteplase versus alteplase) did not modify the association between continuous onset to needle time (P = .161) nor the door-to-needle time (P = .972) or primary clinical outcome. Regarding the probability of achieving a 90-day mRS score of 0 to 1, irrespective of the agent used, each 30-minute reduction in onset to needle time was associated with a 1.8% increase, whereas every 10-minute reduction in door-to-needle time was associated with a 0.2% increase, respectively.³

Tenecteplase is only the second such approval for this indication, following the 2015 approval of alteplase (Activase; Genentech).⁴ Tenecteplase is faster and more simply administered than alteplase, according to Genentech.¹ It is also FDA-approved for the treatment of acute ST-elevation myocardial infarction (known as STEMI) in adults.

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The FDA label for the tenecteplase included important safety information—specifically, the treatment is contraindicated for the treatment of active brain bleeding, for the treatment of STEMI with a history of brain bleeding, and for those with a history of ischemic stroke within 3 months. Additionally, physicians should avoid using this option for patients with the following conditions:

• Patients with active internal bleeding.
• Patients undergoing brain or spinal surgery.
• Patients with a serious head injury within 2 months.
• Patients with a condition that increases the risk of bleeding more than normal.
• Patients with severe, uncontrolled high blood pressure.
• Patients with brain tumor(s), an abnormal connection between veins and arteries in the brain or spinal cord, or an abnormal bulge in the wall of an artery.

Additional Tenecteplase Data

ANGEL-TNK Trial

Earlier this year, late-breaking data from the ANGEL-TNK trial (NCT05624190) of tenecteplase were presented by Xiaochuan Huo, MD, PhD, director of the Neurological Disease Center at Beijing Anzhen Hospital, China, at the 2025 International Stroke Conference (ISC), held February 5-7, in Los Angeles, California. Ultimately, those data showed that the use of intra-arterial tenecteplase after successful endovascular thrombectomy may improve the likelihood of excellent neurological outcomes among patients with acute large vessel occlusion (LVO) treated between 4.5 to 24 hours.⁵

At 90 days in ANGEL-TNK, 40.5% (n = 51) of patients in the intra-arterial tenecteplase group demonstrated 'excellent' outcome compared with just 26.4% (n = 34) of those in the medical management group (treatment effect, 1.44; 95% CI, 1.06-1.95; P = .02). Mortality was relatively unchanged between the groups, as 21.4% (n = 27) of those in the intra-arterial group and 21.7% (n = 28) in the medical management group died during the 90-day period (treatment effect, 0.99; 95% CI, 0.62-1.58; P = .39).

TIMELESS Trial

Prior to that, data from the TIMELESS trial (NCT03785678) showed that the use of tenecteplase between 4.5 to 24 hours after stroke in patients with occlusions of the middle cerebral artery or internal carotid artery did not result in better clinical outcomes than those with placebo. Despite this, certain subgroups did show greater benefit; TIMELESS was the first study to show that IV thrombolytics could be given up to 24 hours without an increase in brain hemorrhage.⁶

Using the entire cohort in TIMELESS, results showed an adjusted common OR of 1.13 (95% CI, 0.82-1.57; P = .45) for the distribution of scores on the mRs at 90 days for tenecteplase compared with placebo. In a subgroup analysis of patients with occlusion of the M1 segment (which was notably not powered for conclusions), 45.9% of those in the tenecteplase achieved functional independence vs 31.4% of those on placebo (adjusted OR, 2.03; 95% CI, 1.14-3.66). Compared with placebo, this subgroup of patients had an adjusted common OR of 1.59 (955 CI, 1.00-2.52) for mRs scores.⁷

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. Menon, Bijoy KSrivastava, Abhilekh 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
3. Singh N, Almekhlafi MA, Bala F, et al. Effect of Time to Thrombolysis on Clinical Outcomes in Patients With Acute Ischemic Stroke Treated With Tenecteplase Compared to Alteplase: Analysis From the AcT Randomized Controlled Trial. Stroke. 2023;54(11):2766-2775. doi:10.1161/STROKEAHA.123.044267
4. Alteplase (Activase). FDA Label. Revised February 2015. Accessed March 3, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/103172s5203lbl.pdf
5. Removing large brain artery clot, chased with clot-buster shot may improve stroke outcomes. News release. American Stroke Association. February 7, 2025. Accessed March 3, 2025. https://newsroom.heart.org/news/removing-large-brain-artery-clot-chased-with-clot-buster-shot-may-improve-stroke-outcomes
6. Albers GW, Purdon B, Yang M, et al. Subgroup analyses from the TIMELESS trial. Presented at: International Stroke Conference; February 7-9, 2024; Phoenix, AZ. LB23.
7. Albers GW, Jumaa M, Purdon B, et al. Tenecteplase for stroke at 4.5 to 24 hours with perfusion-imaging selection. NEJM. Published February 8, 2024. doi:10.1056/NEJMoa2310392