Approval of tenecteplase for stroke in India misguided, says expert

Plans by Indian drugmaker Gennova to launch its generic clot-buster tenecteplase as a treatment for stroke in India are "incomprehensible," according to a leading stroke expert.

Originally developed by Roche and sold under license by Boehringer Ingelheim in India as Metalyse, tenecteplase is used as a treatment for heart attack but is not approved anywhere as an ischemic stroke treatment--other than in India. In fact, the only approved drug therapy for stroke is a clot-busting drug called alteplase, but this is known to have a very narrow therapeutic window, only providing a benefit if given within the first few hours after symptoms start. Boehringer sells alteplase under the Actilyse brand name as a stroke treatment.

Boehringer insists that Gennova should have to conduct its own comparative study with alteplase in order to extend the indications for tenecteplase, but the Indian company is equally adamant, saying that its study met the requirements of the Drug Controller General of India (DCGI).

But a leading stroke expert thinks it is a mistake if India gives the Gennova drug approval for the indication. Kennedy Lees, who is professor of cerebrovascular medicine at the University of Glasgow, told FiercePharma that there is simply not enough evidence to support the use of tenecteplase in stroke.

"Tenecteplase is under trial elsewhere in the world in view of putative advantages over alteplase, but at this stage no adequately powered trial has assessed--let alone established--its safety and efficacy in stroke, neither against control nor for equivalence against alteplase," he said.

That view is shared with Boehringer, which is challenging the Indian government's decision to approve tenecteplase in stroke on the grounds that is based on an open-label study involving just over 100 patients, according to an Economic Times report.

There is some comparative data on the two drugs out there. A Phase II trial published in the New England Journal of Medicine (NEJM) in 2012 with almost 2,700 patients suggested there may be a slight clinical advantage for tenecteplase, but concluded that a larger Phase III trial would be needed before it could be approved for stroke.

Meanwhile, similar conclusions were drawn from the ATTEST trial, published last year in The Lancet, which involved just 355 patients. The investigators suggested tenecteplase's simpler dosing regimen could offer an advantage because "delays between initial bolus and initiation of maintenance infusion are common with alteplase and might compromise effectiveness." However, once again the recommendation was that further study was needed to test the hypothesis.

Prof. Lees was chair of the data and safety monitoring committee for ATTEST, and is forthright in his criticism of the Indian approval on such limited data.

"Even if safe and effective, the dose, time window and effects in marginal groups will require testing in hundreds or thousands rather than tens of patients," he said.

"For a country with as many stroke patients as India and such poor access to specialist stroke care and thrombolysis, to approve use of an inadequately tested drug--simply because it is cheap--is incomprehensible."Gennova says it will sell tenecteplase for stroke at a price of 28,900 rupees (around $430), claiming this will be a significant discount to Boehringer's 70,000-rupee price for alteplase in this indication.

by Phil Taylor | Aug 19, 2016


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