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Efficacy

Metalyse 25 mg is now available for adults for thrombolytic treatment of acute ischaemic stroke within 4.5 hours from last known well and after exclusion of intracranial haemorrhage1

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Non-inferior efficacy to alteplase

In the AcT phase III clinical trial, tenecteplase* demonstrated non-inferior efficacy compared to alteplase for the treatment of AIS2

The primary outcome (% patients with mRS score of 0-1 at days 90-120)†2 occurred in 36.9% of tenecteplase patients, versus 34.8% of alteplase patients (unadjusted RD 2.1% [95% CI -2.6 to 6.9]).2 

The efficacy of tenecteplase* versus alteplase was consistent across subgroups by age, sex, and National Institutes of Health Stroke Scale (NIHSS) status.2

modified-rankin-scale

This figure is made by Boehringer Ingelheim based on ref. Menon BK, et al. Lancet 2022; 400:161-169.

AcT was a multicenter, open-label, parallel-group, registry-linked, RCT (Randomized Controlled Trial), in which 1600 patients were enrolled from 22 primary and comprehensive stroke centres across Canada and randomly assigned to tenecteplase (as a weight-tiered bolus dose, based on 0.25 mg/kg, to a maximum of 25 mg, n=816) or alteplase (0.9 mg/kg to a maximum of 90 mg, n=784). Patients 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4.5 hours of symptom onset, and eligible for thrombolysis per Canadian guidelines, were included. The primary outcome in AcT was a mRS score of 0-1 at 90-120 days after treatment, assessed via blinded review in the ITT (Intention-To-Treat) population.2

In the EXTEND IA TNK Phase II study of AIS patients with large vessel occlusion, tenecteplase showed greater reperfusion before mechanical thrombectomy compared to those receiving alteplase3

Treatment with tenecteplase was associated with significantly higher odds of achieving the primary outcome (reperfusion of > 50% of the involved ischemic territory)# versus alteplase (incidence difference was 12 % [95% CI, 2% - 21%]; incidence ratio, 2.2 [95% CI, 1.1 to 4.4]; P = 0.002 for noninferiority; P = 0.03 for superiority).3

Efficiency Page

This figure is made by Boehringer Ingelheim based on ref. Campbell BCV, et al. N ENgl J Med. 2018; 378:1573-82.

The EXTEND-IA TNK trial is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded outcome trial involving patients with ischemic stroke within 4.5 hours after onset who had LVO of the internal carotid, middle cerebral, or basilar artery and who were eligible to undergo IV thrombolysis and endovascular thrombectomy. Patients were randomly assigned in a 1:1 ratio to receive IV tenecteplase (0.25 mg/kg) or alteplase (0.9 mg/kg). Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome of substantial reperfusion was defined as the restoration of blood flow to > 50% of the involved territory or an absence of retrievable thrombus in the target vessel at the time of the initial angiographic assessment. Perfusion was assessed with the use of the mTICI (Modified treatment in cerebral infarction) classification (scores range from 0 [no flow] to 3 [normal flow]).3

Door-To-Needle

This figure is made by Boehringer Ingelheim based on ref. Burgos A. M. and Saver J. L. Stroke 2019; 50:2156-2162.

A meta-analysis of 5 randomised controlled trials further supported that tenecteplase is non-inferior to alteplase in efficacy for the treatment of AIS4

The primary end point was crude cumulative rates of disability-free (mRS score, 0-1) 3-month outcome.4

In an informal, random-effects meta-analysis, the risk difference was 4% (95% CI, -1% to 8%).4

A systematic literature search and formal meta-analysis were conducted per PRISMA guidelines, adapted to noninferiority analysis. The primary outcome was freedom from disability (mRS score, 0–1) at 3-months, and additional efficacy and safety outcomes were analysed. The systematic search identified 5 trials enrolling 1585 patients (tenecteplase=828, alteplase=757). All alteplase patients received standard 0.9 mg/kg dosing, while tenecteplase dosing was 0.1 mg/kg in 6.8%, 0.25 mg/kg in 24.6%, and 0.4 mg/kg in 68.6% of participants.4

Footnotes

  • *
    Tenecteplase was administrated within 4.5 hours after onset of stroke symptoms, as a one-time decile-weight-tiered bolus dose, based on 0.25 mg/kg for the maximum weight at each tier: < 60 kg, 15 mg tenecteplase; ≥ 60 to < 70 kg, 17.5 mg; ≥ 70 to < 80 kg, 20 mg; ≥ 80 to < 90 kg, 22.5 mg; and ≥ 90 kg, 25 mg.2
  • †
    The mRS score is a seven-point ordered categorical scale from 0 to 6 for functional neurological outcome, with 0 indicating no neurological symptoms and 6 indicating death.2
  • ‡
    Four patients did not have initial intracranial endovascular thrombectomy images.2
  • §
    Scored as follows: 0, primary occlusive thrombus remains same; 1, debulking of proximal part of the thrombus but without any recanalisation; 2a, partial or complete recanalisation of the primary thrombus with occlusion in major distal vascular branch; 2b, partial or complete recanalisation of the primary thrombus with occlusion in minor distal vascular branch, or partial recanalisation of the primary thrombus with no thrombus in the vascular tree at or beyond the primary occlusive thrombus; and 3, complete recanalisation of the primary occlusive thrombus with no clot in the vascular tree beyond. rAOL was not assessable in six patients because of missing initial intracranial angiography or missing baseline CT angiography images.2
  • #
    The primary outcome of substantial reperfusion was defined as the restoration of blood flow to > 50% of the involved territory or an absence of retrievable thrombus in the target vessel at the time of the initial angiographic assessment. Perfusion was assessed with the use of the mTICI classification (scores range from 0 [no flow] to 3 [normal flow]).3
  • ‖
    Scores range from 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability, 2 slight disability, 3 moderate disability, 4 moderately severe disability, 5 severe disability, and 6 death.2
  • **
    Adjusted for age, sex, baseline stroke severity, stroke symptom onset-to-needle time, and source registry as fixed effects variables, and site as a random effects variable.2
  • AIS = Acute ischemic stroke, CI = Confidence Interval, eTICI = extended Thrombolysis in Cerebral Infarction, mRS = modified Rankin Scale, rAOL = revised Arterial Occlusive Lesion score, RD = Risk Difference.
  • Fibrinolytic treatment of acute ischaemic stroke (within 4,5 hours of last know well and after exclusion of intracerebral haemorhage by suitable imaging technology)
References

  1. Metalyse® European Summary of Product Characteristics.12/2023

  2. Menon BK, et al. Lancet 2022; 400:161-169.

  3. Campbell BCV, et al. N Engl J Med. 2018; 378:1573-82.

  4. Burgos A. M. and Saver J. L. Stroke. 2019; 50:2156-2162.

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