开发抗凝血最佳药物竞赛未休

Pipeline
A Blood-Thinner Best Seller?
Robert Langreth, 12.07.07, 6:00 AM ET'

The race to develop new blood thinners is going into overdrive.

Some of the biggest drug companies in the world are moving into final-stage trials of new anti-clotting drugs aiming to be safer and more convenient then existing remedies.

Johnson & Johnson (nyse: JNJ - news - people ), Bayer (nyse: BAY - news - people ), Bristol-Myers Squibb (nyse: BMY - news - people ) and Eli Lilly (nyse: LLY - news - people ) are all rushing to test the new drugs, called factor 10a inhibitors. The pills aim to replace a finicky, fifty-year-old drug called warfarin.

While effective, warfarin is incredibly tricky for doctors to use because there is only a tiny margin between giving too little and giving too much, risking uncontrolled bleeding. It is slow to kick in and interacts with many foods and other drugs. The new drugs aim to avoid these problems. And unlike Sanofi-Aventis' (nyse: SNY - news - people ) big-selling injectable blood thinner, Lovenox, they can be given as pills.

Drug industry research firm Decision Resources predicts that, if successful, the new drugs could double the size of the anti-coagulant market from $3 billion last year to $7.4 billion in 2016. The factor 10a inhibitors have \"home run potential,\" says Citigroup analyst Matthew Dodds in a recent report. The drugs work by blocking an enzyme called factor 10a that helps spur the production of a crucial clot-promoting protein called thrombin.

Anti-clotting drugs represent one of the few big sales opportunities at a time when the drug industry researchers are struggling to come up with new drugs. Genentech's (nyse: DNA - news - people ) bid to get its Avastin colon cancer drug approved in breast cancer was rejected by a Food and Drug Administration panel earlier this week. Drug approval numbers are at a multiyear trough.

Rivaroxaban, invented by Bayer and soon marketed by Johnson & Johnson in the U.S., is among the farthest along of the new clot-stoppers. At a big meeting of hematologists in Atlanta this coming weekend, Johnson & Johnson and Bayer are scheduled to present results of three big trials showing that rivaroxaban is better than Sanofi-Aventis' Lovenox at preventing leg vein clots in patients getting knee or hip replacement surgery.

The presence of such clots, a problem called deep vein thrombosis, is dangerous because they can eventually dislodge and end up causing fatal pulmonary embolisms, clots in the main artery leading from the heart to the lung. Abstracts of these trials were published a few weeks ago in advance of the meeting, but J&J and outside researchers who did the trial are prohibited from commenting in advance of the meeting.

Johnson & Johnson is finishing up a required U.S. trial and hopes to apply for approval for preventing leg clots in the second half of 2008. (Bayer has already filed for European approval.)

Meanwhile, J&J and Bayer have begun a giant 14,000-patient trial in a potentially far bigger market: preventing strokes in patients with a common heart rhythm problem, atrial fibrillation. Some 2.9 million Americans suffer from this problem, estimates Citigroup. But studies have found that only around half of the eligible patients end up on warfarin because of the hassles involved in using it.

Bristol-Myers, with partner Pfizer (nyse: PFE - news - people ), is testing factor 10a blocker apixaban in a giant 15,000-patient trial on preventing stroke. Both of these trials directly compare the new drugs to warfarin. Meanwhile, at an analyst meeting in New York yesterday, Eli Lilly said it's also testing a factor 10a drug and plans to begin first final-stage trials in 2009.

All sorts of issues could still hold up approval of the new drugs, given an increasingly risk-averse FDA. One big concern: whether the drugs cause liver problems. A few years ago, AstraZeneca (nyse: AZN - news - people ) touted its new blood thinner drug Exanta as a breakthrough that could replace warfarin. But the FDA rejected it after regulators saw signs it could cause liver failure; the drug eventually was withdrawn in Europe as well. Expect scrutiny of the J&J/Bayer trials at this weekend's hematology meeting as Wall Street analysts look closely for any hint of liver problems. No signs of such problems have emerged in data released so far.