LOS ANGELES — Tenecteplase (TNKase) is a more powerful thrombolytic for large vessel acute ischemic stroke than alteplase (Activase) but just as safe, the EXTEND-IA TNK trial showed.
Tenecteplase increased the proportion of patients headed to endovascular therapy who had substantial reperfusion on the initial angiogram, with TICI 2b/3 flow or no retrievable thrombus at that point, compared with alteplase (22% versus 10%, adjusted OR 2.6, P=0.002 for non-inferiority and P=0.02 for superiority).
The number needed to treat was 9.1 to avoid one thrombectomy procedure, Bruce Campbell, MBBS, PhD, of Australia’s Royal Melbourne Hospital, reported here at the International Stroke Conference.
Functional outcomes on the modified Rankin Scale at 90 days were also significantly shifted toward less disability in the tenecteplase group after adjustment for age and initial stroke severity (ordinal cOR 1.7 95%CI 1.0-2.8, P=0.037).
In terms of safety, mortality trended in favor of tenecteplase (10% versus 18%, OR 0.44, P=0.08), with an identical 1% rate of symptomatic intracranial hemorrhage and a similar rate of parenchymal hematoma between groups (6% versus 5%, P=0.76).
Tenecteplase, which is currently approved for myocardial infarction, also has other features to recommend it, noted Campbell: The convenience of a single bolus administration that avoids complications for transferring patients during infusion, as required for alteplase, when they need thrombectomy at a capable center. The drug is lower cost, with a U.S. wholesale at $5,861.87 per 50 mg (dosing in the trial was 0.25mg/kg) compared with $8,800.36 per 100 mg alteplase (dosed at 0.90 mg/kg in the trial). And it spares some patients from needing thrombectomy, which also trims costs.
However, there’s little commercial momentum to push for FDA approval of tenecteplase beyond its current indication.
Genentech markets both tenecteplase and alteplase in the U.S. While it has been raising the price on alteplase, Genentech doesn’t plan to work toward a stroke indication for tenecteplase, as it told MedPage Today in November when data suggesting it was at least on par with alteplase were reported. The company had no role in the current trial, which was funded mainly by the Australian government.
“It’s been a slow journey,” commented Bruce Ovbiagle, MD, of the Medical University of South Carolina in Charleston. He called the EXTEND-IA TNK data “impressive. It was a noninferiority design but ended up being superior in so many ways.”
Still, he predicted it would likely take a U.S. trial to move things forward.
“If it was FDA approved, we would look at the results, see how it fits in our system. If tenecteplase is faster, better, and safer we would probably pick it,” commented Mark Alberts, MD, of Hartford Healthcare.
EXTEND-IA TNK included 202 patients in Australia and New Zealand with a large vessel occlusion eligible for thrombectomy randomized to open-label treatment with blinded-endpoint assessment.
Two non-thrombectomy trials are underway but both outside the United States — TASTE (from centers in Australia, Taiwan, Canada, and Europe) and ATTEST-2 (out of England and Scotland) — testing 0.25-mg/kg tenecteplase head-to-head against alteplase.
The trial was funded chiefly by the Australian government. Medtronic “provided an unrestricted grant for trial infrastructure but had no role in study design conduct or analysis.”
Campbell and Ovbiagle disclosed no relevant relationships with industry.