STOCKHOLM The $10 billion-plus race to oust warfarin, a 65-year-old heart medicine originally developed as rat poison, remains wide open following strong clinical trial results from rival new anticoagulant drugs.
With no clear winner so far in a three-way battle between Bayer, Bristol-Myers and Boehringer Ingelheim, doctors say a complex -- and potentially confusing -- market could develop, as each new drug focuses on different patient groups.
"This space will get complicated very quickly now because you will be dealing with drugs that have different mechanisms," said Clyde Yancy of the Baylor Heart and Vascular Institute in Dallas and past president of American Heart Association.
"I think many practitioners will become perplexed, confused, and the real concern is: are we at risk of making some major mistakes here? The complications are very real if you are dealing with bleeding risk."
Unlisted Boehringer will learn its chances of replacing warfarin in the key market for preventing stroke in patients with atrial fibrillation, a common arrhythmia, when a U.S. advisory panel reviews its drug Pradaxa on September 20.
But Xarelto, from Bayer (BAYGn.DE) and its partner Johnson & Johnson (JNJ.N), and apixaban, being developed by Bristol-Myers Squibb (BMY.N) and Pfizer (PFE.N), remain firmly in the race following good clinical results on Tuesday.
"You have here good drug alternatives, which is what clinicians need," Fausto Pinto of Lisbon University Medical Schoo told Reuters.
He said the latest studies on Xarelto and apixaban showed clear benefits in particular indications and demonstrated the new drugs could be safely given, but neither was definitive. In both cases the tests were part of wider development programs.
Pinto chaired the program committee for this week's European Society of Cardiology's congress in Stockholm, which chose to highlight research on the drugs as "hot line" sessions.
Industry analysts estimate the warfarin-replacement market at more than $10 billion a year and possibly up to $20 billion.
Medical experts have cheered the arrival of a new generation of anti-clotting drugs, since it is hard to maintain the right balance of warfarin in patients and the drug also interacts badly with certain foods and other medicines.
"Patients and physicians have been begging for a warfarin replacement," according to Ralph Brindis, president of the American College of Cardiology.
"I don't know which one is going to win or lose among that family but the body of evidence about safety and efficacy is growing and growing."
While the first new oral drug to make it to market as a stroke preventer will have a clear marketing advantage, this will not be the end of the story.
In an era of austerity and ever-greater focus on costs, pricing will also be a key determinant of market share, as will doctors' concerns about making sure patients adhere to treatments that can mean the difference between life and death.
In that respect, a simpler dosing regimen could be a significant advantage, Brindis said.
Xarelto needs to be taken only once a day, while Pradaxa and apixaban are twice-daily pills.
Although the three rivals drugs are competing in the same space, different clinical trials address different groups of patients and regulatory approvals -- at last initially -- are likely to be confined to certain market segments.
Doctors are, however, free to prescribe licensed medicines "off label" in non-approved indications, which could be a danger, Pinto said, making clear guidelines from medical societies very important.
Shares in both Bayer and Bristol rose on Tuesday in reaction to the latest positive clinical trial news as analysts latched on to data that underpinned upbeat sales forecasts.
Jeff Holford of Jefferies said apixaban's 52 percent risk reduction versus aspirin for stroke compared favorably with Pradaxa, suggesting eventual potential peak annual sales of more than $6 billion for apixaban several years out.
For Xarelto, the impressive data in treating deep vein thrombosis augured well for upcoming data in November on stroke prevention, where the drug could sell $2.8 billion, he added. Jefferies also expects another $800 million in peak sales for Xarelto in venous thromboembolism.
(Editing by David Cowell)