Biotech Values

[DewDiligence]

Darexaban Flunks Phase-2 Trial in ACS

[Astellas Pharma’s Darexaban (a/k/a YM150) is not necessarily a bad drug, but it would seem to be a day late and a dollar short in the competition against Eliquis, Xarelto, and Pradaxa. None of these drugs to date has fared well in ACS. The phase-2 trial discussed in this newswire is at http://clinicaltrials.gov/ct2/show/study/NCT00994292 .]

http://www.reuters.com/article/2011/08/30/heart-astellas-idUSL5E7JU0CX20110830

›Tue Aug 30, 2011 4:32am EDT
By Ben Hirschler

PARIS, Aug 30 (Reuters) - An experimental anti-clotting drug from Japan's Astellas increased bleeding two- to four-fold in a mid-stage clinical study of heart patients, raising questions about its role in treating those with acute coronary problems.

The new oral anticoagulant, known as darexaban or YM150, also showed no sign of reducing the risk of heart attacks and strokes, although researchers said the 1,279-patient Phase II study was too small to evaluate efficacy with any certainty.

While the results are disappointing, the outcome does not necessarily mean darexaban has no future, Dr Gabriel Steg of the Hospital Bichat in Paris, who led the research, said on Tuesday.

The Astellas medicine belongs to the same so-called Factor Xa inhibitor drug class as Bristol-Myers Squibb and Pfizer's Eliquis, which on Sunday produced impressive results in another group of patients -- those at risk of stroke because they have dangerously irregular heart rhythms.

Before succeeding in this atrial fibrillation (AF) population, Eliquis had also failed in patients with acute coronary syndrome (ACS) due to excessive bleeding [#msg-56880416].

Patients with ACS, which typically involves chest pain and risk of heart attack due to blocked arteries, are given antiplatelet blood thinners to reduce their risk danger of clots. But doctors are interested to find out if the new generation of oral anticoagulants might also help. The latest study raises fresh doubts about the strategy.

"I think we have a series of mixed signals. It is probably a little too soon to forgo the idea of adding anticoagulants to anti-platelet therapy," Steg told reporters at the European Society of Cardiology annual meeting.

Various doses of darexaban were tested on top of dual antiplatelet therapy in the Phase II trial and bleeding increased as dosing increased.

Dr David Holmes of the Mayo Clinic, who is also president of the American College of Cardiology and was not involved in the research, said it was still worth investigating the use of anticoagulants in ACS, although a low dose of darexaban would be needed in any future tests.

Darexaban is also being studied for stroke prevention in AF patients [http://clinicaltrials.gov/ct2/show/study/NCT00938730 ] and it has already produced good results in preventing the risk of blood clots after orthopaedic surgery. Still, it is a late entrant into an increasingly crowded marketplace, with rivals including Boehringer Ingelheim's Pradaxa, Bayer and Johnson & Johnson's Xarelto, and Bristol and Pfizer's Eliquis -- as well as a late pipeline product called edoxaban from Daiichi-Sankyo .

Last February, Astellas withdrew its Japanese filing for darexaban for use after surgery, following a request from regulators for additional clinical studies. The company has said it will decide on future plans for the drug based on the outcome of discussions with potential global partners.‹