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The $12 Billion Battle At Pharma’s Bleeding Edge

http://blogs.forbes.com/matthewherper/2010/09/17/the-12-billion-battle-at-pharmas-bleeding-edge/

On Monday, things start getting hot for a trio of drugs that could be the pharmaceutical industry’s salvation.

Drug companies have struggled to replace the aging cholesterol, blood pressure, and depression treatments that were once their best sellers, and retreated into high cost specialty medicines for rare diseases. But there is a giant exception to this rule: the field of blood-thinners, which could be about to explode.

More than 2 million Americans suffer from an condition called atrial fibrillation, in which sporadic heart rhythm leads to pooling blood and the creation of clots that increase the risk of stroke more than five-fold. The only way to reduce this risk is with warfarin, a cheap generic that is difficult to given and can cause too much bleeding.

Now, after years of effort, several of the world’s largest pharmaceutical companies seem close to launching warfarin replacements. C. Anthony Butler, the pharmaceutical analyst at Barclay’s, forecasts 2021 sales of $12 billion for these new medicines.

The first of these warfarin replacements, from Boehringer Ingelheim, goes before an FDA advisory committee on Monday. Another from Bayer and Johnson & Johnson, will get a coming out party at the American Heart Association meeting in November, when data from its key study will be released. A third pill, from Bristol-Myers Squibb and Pfizer, is trailing slightly behind, but Butler expects it to be the biggest winner of the three because of what, so far, looks like a less worrisome bleeding profile.

Both Bayer’s drug, Xarelto, and Bristol’s, apixaban, presented promising data at a recent cardiology meeting in Europe. But those studies don’t seem likely to get the drugs approved in the U.S. Monday’s FDA meeting on Boehringer’s Pradaxa is the first time we get a really good look at one of these compounds.

Pradaxa’s been building buzz for a while now, ever since a study showing it prevented strokes as well as warfarin without added bleeding was published in the New England Journal of Medicine along with an editorial supporting approval. It works differently from the other two replacements, blocking the protein thrombin; Xarelto and apixaban knock out another clotting factor, called Xa (that’s the Roman numeral ten followed by the letter a.)

The FDA released briefing documents related to the Pradaxa panel yesterday, and they let some of the hot air out of Boehringer’s balloon. The FDA reviewers questioned the effectiveness of the drug’s lower dose, and it also seems very uncomfortable with aspects of the design of the company’s key trial, which was open-label, meaning patients knew whether they were getting warfarin. This could force Boehringer to market Pradaxa as equivalent to warfarin, not better.

Proof the FDA is treading carefully: Steven Nissen of the Cleveland Clinic is serving on the panel. He’s become famous as a safety advocate. Years ago, serving as an FDA advisor, he led an effort on another FDA advisory panel that kept another potential warfarin replacement, Exanta, off the market. It was eventually withdrawn worldwide because of the very liver toxicity that worried Nissen.

The most likely outcome: Pradaxa gets approved at both doses, but with a weak label. This would also, as it happens, be the best outcome for Bayer/J&J and Pfizer/Bristol. A non-approval probably raises the bar too high for the other entrants, but a bad label gives them something they can beat in the marketplace. Unlike Boehringer’s study, the other companies are testing their medicines in trials in which patients are blind to what treatment they are receiving.

In a big new drug market, being first isn’t always best. Take the market for cholesterol medicines, which Merck established, and then, several years later, Pfizer stole with Lipitor, a more potent drug. Right now, drug #3, from Pfizer and Bristol, is getting the most buzz. And Merck is trying to repeat Pfizer’s old trick with its own blood-thinner, being developed with Portola Pharmaceuticals. It’s years behind, but would be the first of these drugs with once-a-day dosing.