Boehringer stroke drug proves a winner in trial
Barcelona, August 30, 2009
Patients at risk of stroke due to an erratic heartbeat should soon have a viable alternative to 50-year-old warfarin, after a new pill from Boehringer Ingelheim beat expectations in a major clinical study.
The strong showing for the unlisted German company's drug Pradaxa impressed experts attending the annual meeting of the European Society of Cardiology (ESC) and promises to change clinical practice in the management of atrial fibrillation (AF).
It also sets a high bar for Bayer and Johnson & Johnson, whose rival drug and big blockbuster hope Xarelto is about a year behind in development.
A pivotal trial involving more than 18,000 patients found a 150 milligram dose of Pradaxa, or dabigatran, given twice daily reduced the risk of stroke and systemic embolism by 34 percent compared to warfarin.
There was no increase in the risk of major bleeding, a common problem with anticoagulants, and there were no signs of liver damage, an issue that sank AstraZeneca's warfarin replacement candidate Exanta five years ago.
'These results are very good,' said Fausto Pinto, director of the Lisbon Cardiovascular Institute and programme chairman of the ESC, who was not involved in the trial. 'It's a very good alternative to warfarin and will probably replace warfarin.'
Industry analysts believe oral anticoagulants that can be used instead of warfarin represent a multibillion opportunity for drugmakers, with some predicting the market could eventually be worth more than $10 billion a year.
Doctors have long wanted an alternative to warfarin, which was first developed as rat poison and is difficult to use. Patients need regular blood tests and must avoid certain foods.
Yet the drug, sold under the brand name Coumadin by Bristol-Myers Squibb and also available as a cheap generic, has remained the gold standard for patients with AF.
The condition causes the two upper chambers of the heart to quiver instead of beating properly, resulting in blood pooling and potentially forming clots that can cause a stroke.
'We've been looking for two decades for an alternative to warfarin,' said Ralph Brindis, president-elect of the American College of Cardiology and senior adviser for Northern California at Kaiser Permanente, a health maintenance organisation.
'(Now) the Holy Grail is maybe obtained that you can have a drug that is safe, efficacious and does not require frequent blood monitoring. It could be a huge advance.'
Pradaxa was not without problems, however. Patients taking the new drug often suffered dyspepsia, which caused some to drop out of the trial, and there was also a puzzlingly higher number of heart attacks seen in the Pradaxa arm compared to warfarin.
Coupled with the fact that Boehringer's study was open-label rather than doubled-blinded -- meaning patients and doctors knew which drug was being used -- the side effects mean regulators will study Pradaxa very closely before approving it.
Still, if all goes well the new medicine could be on the market by the end of next year. Stuart Connolly of Canada's McMaster University, one of the principal investigators for the study presented at the meeting in Barcelona, said the clinical study had 'exceeded all our expectations'.
The results were published online in the New England Journal of Medicine. Other oral anticoagulants in development include Pfizer and Bristol's apixaban and Merck's betrixaban, both of which are further behind Pradaxa and Xarelto in testing. - Reuters