Patients at risk of stroke due to an irregular 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% 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.
A lower 110 mg showed similar efficacy to warfarin and carried a lower bleeding risk.
"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.
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.
Better than rat poison
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 millions of 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, senior adviser for Northern California at Kaiser Permanente.
"(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."
Stuart Connolly of Canada's McMaster University, one of the principal investigators, said the results - which were also published online in the New England Journal of Medicine - had "exceeded all our expectations".
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.
"I would anticipate the FDA (US Food and Drug Administration) would come forward with a somewhat restrictive labelling," said Clyde Yancy, president of the American Heart Association.
Still, if all goes well, Boehringer hopes its new medicine will reach the market by the end of next year.
After that the focus will switch to pricing, where experts predict a tussle. Pradaxa will be going up against a cheap generic in warfarin, but one which requires regular monitoring, resulting in a monthly cost of anything from $75 to $750.
"I think insurers are going to be putting a lot of pressure on to not pay for the (new) drug for a period of time," said Alfred Bove, president of the American College of Cardiology. "It's going to be a battle."