Boehringer’s Blood Thinner Dabigatran (Pradaxa) Unanimously Endorsed
Sep22

Boehringer’s Blood Thinner Dabigatran (Pradaxa) Unanimously Endorsed

After last week's Meridia and Lorqess drama, I could've really used some good news from an FDA panel. And on Monday, I got it- in the form of a unanimous endorsement for a new blood thinner. The drug getting the love is dabigatran etexilate, which was developed by family-owned Boehringer Ingelheim and will be marketed as Pradaxa if approved. It's one of a cadre of drugs trying to replace warfarin (also known as coumadin), a medication that has been on the market for over 50 years and is among the most difficult to manage. Warfarin prevents formation of blood clots and can reduce ongoing clots. Doctors prescribe it to prevent painful leg clots in patients getting hip or knee replacements, to prevent stroke in patients with an abnormal heart rhythm called atrial fibrillation, and more. We recently wrote about how warfarin is a dirt cheap and effective medication, but it interacts with a plethora of foods, herbal supplements, and other drugs. Pradaxa is already approved in several countries outside the U.S. for short-term use, preventing leg clots in patients getting hip or knee replacements. The drug blocks thrombin, a protease enzyme that sits near the end of the complex biochemical pathway known as the coagulation cascade. Just about all of the drugs being developed to replace warfarin, at least the ones toward the end of the pipeline, target either thrombin or Factor Xa, the protein immediately before thrombin in the pathway. FDA's cardiovascular and renal drugs advisory committee voted 9-0 in favor of approving Pradaxa for preventing stroke in patients with atrial fibrillation. (Boehringer-Ingelheim press release) This will be a longer-term stint on Pradaxa than post-hip or knee surgery patients typically experience. So the most important part of the panel's discussion, to me, was their assessment of the drug's effects on the liver. That's because in 2006, another thrombin blocker called ximelagatran, developed by AstraZeneca, was pulled from the market because of liver toxicity. When you dig into the briefing documents that FDA provided to the panel, you find this blurb on page 103: Based on these data, the risk of severe drug induced liver injury from dabigatran appears to be low. Because the perceived risk is low and frequent liver monitoring may not prevent serious cases from occurring (even if an association did exist), regular monitoring of liver tests is not recommended. So it seems that ximelagatran's liver issues may not be a class-wide problem. Still to be determined is what doses of the drug might be approved- read this post by Pharmalot for an assessment of why doses matter. FDA is expected to make its call on...

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Bayer to Eliminate Unsightly Chin Fat
Sep01

Bayer to Eliminate Unsightly Chin Fat

As my husband and I recently looked through photos of our wedding, he kept repeating the same thing: “Yikes, check out my triple chin.” Click. “Another triple chin.” Click. “Hmm, maybe I need to work out.” In reality, his perceived folds of flab were a result of unfortunate camera angles (I swear, dear. Your chin is splendid.). But if a day comes when he genuinely suffers from chin bulge, Bayer might have just the solution. Yesterday, the company agreed to fork over $43 million upfront and upwards of $300 million in milestone payments for Kythera Biopharmaceuticals’ ATX-101, an adipolytic agent “designed to reduce small volumes of facial fat.” Yes, that’s right, folks: it’s a chin fat drug. Because I tend to cover pharmaceuticals that are more in the disease-modifying category rather than those in the aesthetics-modifying category, I was pretty shocked by the price tag. Then I took a look at Allergan’s sales forecast for its wrinkle smoother Botox—the company is predicting it will bring in about $1.3 billion this year. (Well, that’s before subtracting out the $600 million Allergan agreed to pay today to settle criminal and civil charges related to the marketing of Botox.) In other words, the potential market for ATX-101 seems pretty vast. Indeed, I imagine my husband isn’t the only one to look at a photo (poorly angled or not) and cringe. ATX-101 is in Phase II studies, and seems to be administrated in a relatively painless injection. All this made me wonder how one goes about getting rid of small fat deposits without, well, sucking them out. It looks like the folks at Kythera, which is conveniently based in Los Angeles, first thought the active component in the formulation of ATX-101 was phosphatidylcholine, a major component of biological membranes that sports a polar head and fatty acid tails. However, further studies showed that deoxycholate, a secondary bile acid put into the formulation to make the phosphatidylcholine micelles soluble, was actually the secret to getting rid of unsightly chin fat. Deoxycholate, a detergent, causes a shift in the osmotic balance of a cell--in other words, water rushes into the fat cell, causing it to burst.  The finding was curious, as deoxycholate appeared to be only affecting fat tissues when administered in vivo. Kythera eventually determined that deoxycholate isn’t necessarily selective for fat cells, but that tissues in the subcutaneous fat that are protein rich are resistant to its effects. Hence, when administered locally, it appears to be able to get rid of the fat without impacting other tissues. And there you have it, drug goes in, fatty chin goes out. Since later stage trials...

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Chemicals In The Steel City
May14

Chemicals In The Steel City

Earlier this week I attended Pittsburgh Chemical Day. The event is a one day meeting followed by a gala dinner. Local Pittsburgh firms—Bayer, Lanxess, Nova, Koppers--put it on. Many other firms attend from out of town, most of them from the East Coast. The event is also heavily attended by chemical distributors. The organizers have complained that attendance for Pittsburgh Chemical Day, which has been held for 43 years, has been waning. They opined that it was emblematic of the decline in the U.S. chemical industry as a whole. But from my perspective, it wasn’t so bad. Although the event seemed scaled down from the last time I attended—in 1999—they did get about 400 people to show up. And dinner was sold out that night. From what I overheard, they even had to add more tables. The keynote speaker at the dinner was Greg Babe, CEO of Bayer Corp., the U.S. arm of German pharmaceutical, polymer, and agricultural chemical maker Bayer AG. Babe called for a renewal of U.S. manufacturing and a reversal of the thinking that says that in another ten years, the U.S. chemical industry will be irrelevant on the global stage. He did point fingers at the public, saying their indifference about whether chemical manufacturers move capacity overseas is part of the problem. The public clamors to help other industries, like car makers—as when Chrysler and GM got bailed out right alongside the troubled banks. “The big three has their problems, but lack of public support isn’t one of them,” he says. Babe said that the industry needs to do a better job of communicating with the public about accidents and contamination. He even referenced a 2008 incident where an explosion killed two workers and nearly ruptured a methyl isocyanate (MIC) tank at Bayer’s plant in Institute, West Virginia. MIC was the chemical behind Union Carbide’s Bhopal disaster in 1984. “We fell short both in terms of communicating the incident and keeping stakeholders apprised of the latest developments,” he said. This may sound a little like blaming the public for the chemical industry’s problems. It is the chemical industry executive themselves that decide to take their capital and invest it in the Middle East and Asia. And they do so for the relative competitive advantages those places offer. The public and the chemical industry making nice would indeed be helpful, but not helpful enough to reverse that momentum all by itself. On the other hand, at an earlier press conference Babe made the same point but applied it to American manufacturing more generally. That makes for a better point. People pay lip service to manufacturing moving...

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Underemployed at Big Pharma?
Mar30

Underemployed at Big Pharma?

An article this week in the NYTimes got me wondering about the work prospects for the tens of thousands of scientists laid off by big pharma. The piece profiled several of the so-called “underemployed”—people who in a dismal labor market took jobs for which they were overqualified. A few years back, I followed a group of chemists that lost their jobs when Bayer decided to close the doors of its New Haven, Conn., campus as they searched for new employment. The take away was that it was a snap for folks with a masters degree—or “hands to make molecules”—to find a job, but much tougher for mid-career scientists to find positions. Nearly every PhD ended up leaving the state, and all but three went to biotech firms. At least they found jobs. That was in 2007. Just three years later, I’m wondering how much worse it has gotten out there. The mega-mergers (Pfizer/Wyeth, Merck/Schering-Plough, Roche/Genentech) and the arrival of the patent cliff have prompted a fresh round of research cuts across all of the major players. In theory, this would mean there are even fewer jobs out there and more people looking for ‘em. And with financing tight, it has gotten harder to get the funds to start-up a new venture. For biotechs looking to hire, the employment glut is obviously a boon. When I interviewed the folks at Cambridge, Mass.-based Forma Therapeutics in December, it was clear that it is a great time to be in an expansion mode. And Joseph Gardner, the CEO of Akebia, a tiny company that was borne out of the ashes of P&G’s pharma unit, told me during the JPMorgan Healthcare conference in January that he had opened a satellite office in Ann Arbor, Mich. The move was solely to accommodate four ex-Pfizer scientists that were affected by the closure of the research site there. I’ve heard similar stories from many small- and medium-sized biotechs. Still, it seems the companies adding significant numbers of researchers are few and far between (a situation underscored in our recent story about the lack of jobs in California). The Times piece talks about mid-level managers taking significant steps back in their career to stay in their field, or even ending up at Starbucks. What I’m wondering is whether most biotech or pharma companies will even consider letting someone come in so many levels below where they left off and, if so, whether that arrangement can actually work out. Or are folks looking into new careers? If so, what’s out there? Leave your thoughts in the comments or, if you're shy, feel free to email...

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