Study Demonstrates Noninferiority of Tenecteplase to Alteplase for Treatment of Acute Ischemic Stroke

Study results published in JAMA Network demonstrated that TNKase (tenecteplase; Genentech, South San Francisco, CA) is noninferior to Activase (alteplase; Genentech, South San Francisco, CA) for the treatment of acute ischemic stroke (AIS) in individuals eligible for intravenous thrombolysis when administered within 4.5 hours of symptom onset. TNKase is a bioengineered variant of Activase with the advantage of single-bolus administration due to its enhanced fibrin specificity and extended half-life.

The multicenter, active-controlled, parallel-group, randomized, open-label, blinded endpoint, noninferiority phase 2b/3 ORIGINAL trial (NCT04915729), included 1465 participants from 55 neurology clinics and stroke centers across China who had AIS with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 1 to 25 and who were symptomatic for at least 30 minutes without significant improvement. Individuals were randomized 1:1 to receive either intravenous TNKase (0.25 mg/kg; n=732) or Activase (0.9 mg/kg; n=733) within 4.5 hours of symptom onset. The primary endpoint was the proportion of participants with a modified Rankin Scale (mRS) score of 0 or 1 (no symptoms or no significant disability) at day 90 with a noninferiority risk ratio [RR] margin of 0.937.

• 72.7% of individuals treated with TNKase met the primary endpoint compared with 70.3% of individuals treated with Activase (RR, 1.03; 95% CI, 0.97 to 1.09; P=.003).
• Symptomatic intracerebral hemorrhage occurred in 1.2% of patients in both groups.
• 90-day mortality rates were 4.6% in the TNKase group and 5.8% in the Activase group (RR, 0.80; 95% CI, 0.51 to 1.23).