The primary outcome of excellent functional outcome (modified Rankin Scale score 0-1) at 3 months was achieved by 64% of patients randomized to tenecteplase versus 63% on alteplase (OR 1.08, 95% CI 0.84-1.38), Nicola Logallo, PhD, of Haukeland University Hospital in Bergen in Norway, and colleagues reported online in the Lancet Neurology.
While these findings were actually a failure for the superiority-designed phase III trial, Brian Silver, MD, of UMass Memorial Medical Center in Worcester, MA, suggested the findings were actually "encouraging with respect to having an alternative agent that is less expensive."
A recent study of Centers for Medicare and Medicaid data showed that alteplase costs have more than doubled since 2005, to about $6,400 per 100-mg vial in 2014, which was about half of the payment to hospitals in 2013.
While alteplase is off-patent, no biosimilar has been announced as under development and it remains as the only thrombolytic with an indication in acute ischemic stroke. Both tenecteplase and alteplase are marketed in the U.S. by Genentech, which has told MedPage Today it has no plans to develop an indication in stroke for tenecteplase beyond the one it has in acute MI.
"If a non-inferiority study is positive, then I think many people would change drugs not just because of cost, but also because of convenience -- tenecteplase can be given as a bolus over a couple of minutes, while alteplase has to be given as a bolus followed by an infusion over an hour," Silver noted. "Hospital transfer for patients eligible for mechanical thrombectomy would be much simpler."
One surprise in NOR-TEST was the lack of advantage to tenecteplase in intracerebral hemorrhage (ICH), which had been seen in prior studies. Any ICH at 24 to 48 hours occurred in 9% of both groups. Symptomatic ICH at that point occurred in 3% of tenecteplase-treated patients and 2% of alteplase-treated patients (P=0.70).
One reason might have been the fairly low proportion of patients with severe stroke in the trial, which had a lower than expected median NIHSS score at admission of 4, the researchers suggested.
The frequency of serious adverse events overall was identical between groups (26% in both). The 3-month mortality rate was 5% with both treatments, 0.4 mg/kg tenecteplase (to a maximum of 40 mg) and 0.9 mg/kg alteplase (to a maximum of 90 mg).
The 1,100-patient, single-blind trial included acute ischemic strokes eligible for thrombolysis and admitted within 4.5 hours of symptom onset or awakening with symptoms or those eligible for bridging therapy before thrombectomy.
"Since our results might not be completely generalizable to patients with severe neurological impairment at admission, future phase 3 studies should investigate the safety and efficacy of tenecteplase in patients with severe stroke," the researchers wrote.
The study was funded by a grant from the Research Council of Norway.