Roche ends the 30-year US hiatus in new stroke drugs

Against all the odds, Roche's Genentech unit has won FDA approval for its clot-busting drug TNKase as a treatment for acute ischaemic stroke, after all but abandoning the project a couple of years ago.

Fibrin-specific plasminogen activator TNKase (tenecteplase) is the first stroke medicine approved by the FDA in nearly 30 years, joining Roche/Genentech's Activase (alteplase), which is the only other option available.

Tenecteplase is a genetically modified version of alteplase with a higher specificity for fibrin and increased resistance to being inactivated, which extends its half-life in the body. That means it can be administered in a single five-second intravenous (IV) bolus, while alteplase needs an IV bolus followed by a 60-minute infusion.

So-called thrombolytic therapies like alteplase and tenecteplase can be used in the very early stages of a stroke to restore blood flow and limit damage to the brain, but have to be given within a few hours of the onset of symptoms and only after a haemorrhagic stroke caused by a bleed has been ruled out.

TNKase's US labelling recommends initiating treatment as soon as possible and within three hours after the onset of stroke symptoms, a slightly narrower window than the four and a half hours approved in Europe, where the drug is sold as Metalyse by Boehringer Ingelheim.

In 2023, Roche said it was removing TNKase for stroke from its phase 3 programmes after a readout of the TIMELESS trial, but indicated that it would continue to review data from the study and other "internal datasets" to see if there was a way forward.

The approval is based on a large multicentre non-inferiority study – called AcT – which showed that TNKase was comparable to Activase in acute ischaemic stroke patients in terms of safety and efficacy.

The drug has been approved for the treatment of acute myocardial infarction (AMI) by the FDA since 2000, and – while Roche doesn't separate Activase and TNKase sales in its financial reporting – the two products contributed more than CHF 1.2 billion ($1.35 billion) last year.

Genentech's chief medical officer Levi Garraway said that the approval "is a significant step forward and underscores our commitment to advancing stroke treatment options for patients," adding: "TNKase provides a faster and simpler administration, which can be critical for anyone who is dealing with an acute stroke."

Stroke is the fifth leading cause of death, and the leading cause of long-term disability in the US, affecting more than 795,000 people each year.

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