FDA Approves Tenecteplase for Acute Ischemic Stroke

A major milestone has arrived in stroke care with the FDA granting approval for TNKase (tenecteplase), a thrombolytic (or clot-dissolving agent), to treat acute ischemic stroke (AIS) in adults. This is the second stroke medication that Genentech has developed and brought to market—nearly 30 years after alteplase (Activase®).

TNKase is delivered as a single five-second intravenous bolus, a simpler and faster route than the current standard-of-care, alteplase, which requires an IV bolus plus a 60-minute infusion. To support this new indication, Genentech will soon introduce a 25 mg vial configuration of TNKase.

This latest approval springs from the large, multi-center AcT trial, in which TNKase demonstrated safety and efficacy comparable to alteplase for acute ischemic stroke. Conducted by a leading research institution in Canada, the study evaluated adults who presented with disabling neurological deficits within 4.5 hours of symptom onset. No significant differences in modified Rankin scale scores at 90 to 120 days emerged between TNKase and alteplase, and both treatments had similar rates of intracerebral hemorrhage at 24 hours.

Additional support comes from the TRACE-2 study in China, which also reported comparable outcomes between the two therapies. Beyond stroke, tenecteplase is approved for acute ST-elevation myocardial infarction (STEMI). Research continues to explore using tissue plasminogen activators alongside stroke thrombectomy to promote distal reperfusion and further improve neurological outcomes.

Stroke remains the fifth leading cause of death and the leading cause of long-term disability in the United States. Because brain damage progresses rapidly during an acute ischemic stroke, timely treatment is crucial—making the quick five-second bolus of TNKase an important new tool for clinicians.

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Important Safety Highlights

• TNKase (tenecteplase) is now indicated for AIS in adults. Treatment should begin as soon as possible, and within 3 hours of stroke symptom onset.
• TNKase is also indicated to reduce the risk of death associated with STEMI.
• The most frequent adverse reactions include bleeding and hypersensitivity. Patients should report any unusual bruising or bleeding symptoms immediately.
• Certain conditions (e.g., active internal bleeding, serious head injury within 2 months, uncontrolled high blood pressure) can increase the risk of bleeding and are contraindications.
• Allergic reactions have been reported and can be severe or life-threatening.
• TNKase and Activase (alteplase) are both marketed by Genentech in the United States and Canada.

Below is a concise table highlighting some key differences between alteplase and tenecteplase:

Characteristic	Alteplase (Activase®)	Tenecteplase (TNKase®)
FDA Approval for Acute Ischemic Stroke (AIS)	Approved in 1996	Approved in 2025
Administration	IV bolus followed by a 60-minute infusion	Single 5-second IV bolus
Primary Study Supporting AIS Use	Multiple trials, including NINDS	AcT trial (and others, e.g., TRACE-2) demonstrating non-inferiority vs. alteplase
Onset-to-Treatment Window	Within 3 - 4.5 hours (per specific guidelines)	Up to 3 hours recommended in label (some studies explored up to 4.5 hours)
Mechanism	Both are tissue plasminogen activators (tPAs)	Both are tissue plasminogen activators (tPAs)
Dosing Simplicity	Requires bolus plus an infusion (more complex)	Single bolus (faster, simpler administration)
Manufacturer	Genentech (United States/Canada)	Genentech (United States/Canada)
Additional Indication	Used off-label in some cases, originally STEMI approval in 1987	STEMI indication (approved for acute myocardial infarction)
Key Safety Considerations	Risk of bleeding (including intracerebral hemorrhage)	Similar bleeding and hypersensitivity risks; caution with uncontrolled hypertension

Note: Both alteplase and tenecteplase are indicated to dissolve clots in the setting of acute ischemic stroke, but differ primarily in dose administration and infusion time. Always consult prescribing information and clinical guidelines for the most up-to-date usage recommendations.

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Take-Home Key Points

1. TNKase is the first new FDA-approved stroke medication in nearly 30 years.
2. A single five-second intravenous bolus makes TNKase faster and simpler to administer than the hour-long infusion required by alteplase.
3. The AcT trial confirmed TNKase is comparable to alteplase in terms of neurologic outcomes and safety.
4. Genentech now offers the only two FDA-approved medicines for acute ischemic stroke—TNKase and Activase.
5. Prompt treatment is critical in acute ischemic stroke, making quick administration methods an important advance in stroke care.