“In evaluating an anticoagulant,” says heart researcher Michael Ezekowitz, “it’s all about getting the dose right.”

That’s the next big challenge for Merck and its partner Portola as they prepare to advance the closely held South San Francisco biotech’s drug betrixaban into a large-scale clinical trial in the burgeoning race to develop a replacement for the heart drug warfarin.

Ezekowitz, a cardiologist at Lankenau Institute for Medical Research, Wynnewood, Pa., told a packed auditorium at the annual science meeting of the American College of Cardiology on Monday that a daily 40-milligram dose of betrixaban caused significantly fewer cases of major or clinically important bleeding than standard treatment with warfarin. Bleeding rates were similiar to warfarin at 60 and 80 milligrams, said Ezekowitz, who led the study. Side affects included diarrhea and nausea.

The Phase 2 study tested the medicine in patients with atrial fibrillation, a heart rhythm disorder that afflicts some 2.5 million Americans and carries the risk of blood clots that can lead to a stroke.

Warfarin, a half-century old workhorse anticoagulant from Bristol-Myers Squibb and generic companies, effectively prevents such clots. But patients need regular blood checks and frequent dose changes to prevent life-threatening clots or bleeding episodes.

After decades of frustration in the hunt for an effective alternative that doesn’t require monitoring, the pipeline is now full of promise. Boehringer Ingleheim, Daiichi Sankyo and joint ventures between Pfizer and Bristol-Myers and Johnson & Johnson and Bayer all have compounds in development for a global market that some analysts expect will exceed $10 billion by later in the decade.

Merck and Portola trail most of their rivals at the moment, but they believe features of its compound, including once-daily dosing and the fact that Portola is developing an antitode that could quickly turn the drug off in the event of a dangerous bleed, could be advantages for betrixaban if it reaches the market.

First they have to find the dose that hits the sweet spot between too much clotting and too much bleeding. Will a 40-milligram dose with the favorable bleeding risk be strong enough to effectively prevent clots? That’s one big question Merck and Portola will ponder in the months ahead as they plan a trial they hope will lead to the drug’s approval.

Bill Lis, Portola’s new CEO, indicated one possibility is to move more than one dose into a Phase 3 trial. “It’s clear we have an active drug that is safe and tolerable and ready for the next stage of development,” Lis says.

Source: The Wall Street Journal

Popularity: 1% [?]

Will a new FDA warning on Plavix help the personalized-medicine cause, or will it just confuse people? That’s the question the Wall Street Journal Health Blog asks today. A new “black box” warning has been added to Bristol-Myers Squibb/Sanofi-Aventis’ anti-clotting medicine Plavix, which is poorly metabolized by up to 14 percent of patients who use it. Those patients, who have a particular genetic variant, could do better on another anticoagulant or on higher Plavix doses, the warning states.

Perhaps the FDA envisions that doctors will now be more likely to follow its recommendation to test patients for that variant before prescribing Plavix. But do enough doctors have access to the tests? Will they have time to wait for the results? Before such an approach grows common, cardiology associations will have to develop treatment protocols, experts tell the WSJ. Meanwhile, says one Harvard Medical School associate prof, “I expect mass confusion in response to this FDA warning.”

This could be an opportunity for upstart Plavix competitor Effient, from Eli Lilly and Daiichi Sankyo, but that drug carries an increased bleeding risk. Or it could be an opportunity for Medco Health Solutions, which last week said it was expanding its personalized-medicine programming–and planned to extend that program to Plavix at some point. Maybe that point has arrived.

Source: FiercePharma

Popularity: 1% [?]

The FDA says it added its strongest warning today to the label of the widely used bloodthinner Plavix, Bristol-Myers’ best-selling drug, to help physicians treat patients correctly. But the warning could make doctors’ job more difficult.

Docs prescribe Plavix to reduce the risk of heart attacks, strokes and other serious heart problems. The drug prevents dangerous blood clots that can cause those conditions. As a growing number of studies has demonstrated, however, Plavix doesn’t work well in certain patients – those with a genetic variation that makes it difficult for them to metabolize the drug.

The FDA says between 2% and 14% of Plavix users don’t respond well to the drug and might benefit from alternative treatment. Hence the new so-called black-box warning.

Genetic testing could identify the poor responders. But most doctors aren’t well equipped to do genetic testing. They don’t have quick access to the tests. Even if they did, they might not have time in the cases of many patients to wait for results to come back.

What’s more, the FDA has approved only one genetic test, Roche’s AmpliChip, to look for the variation, but not specifically for determining treatment with Plavix. Many laboratories offer other tests, whose quality the FDA says doctors will have to assess before using. Doctors should make sure the tests are at least 98% accurate, FDA officials told reporters.

Christopher Cannon, a Harvard Medical School associate professor and editor-in-chief of Cardiosource, tells the WSJ’s Ron Winslow that heart-doctor associations will need to develop protocols for testing and treatment. The alternatives include increasing the dose of Plavix or switching to bloodthinner Prasugrel from Lilly and Daiichi Sankyo, but Cannon says neither has been tested for that purpose.

“Thus a real conundrum” for patients and their physicians, Cannon said. “I expect mass confusion in response to this FDA warning,” he added.

Plavix, which is also marketed by Sanofi Aventis, is the second-best selling drug world-wide with $8.6 billion in sales in 2008, according to IMS Health.

Source: The Wall Street Journal

Popularity: 1% [?]

While Big Pharma bewails the forthcoming loss of patent protection on many top-selling drugs, the knock-off drug business is rubbing its hands in anticipation. Just witness the Indian pharma industry, which is positioning itself to capture as much of that business as it can.

Considering that nearly $60 billion worth of drugs fall off patent over the next four years, who could blame Indian drugmakers for angling for their share? After all, they’ve spent years building up their generics businesses. “While we are not too much into new drug inventions, we are quite strong in manufacturing formulations and bulk drugs,” J. Jayaseelan of the Indian Pharmaceutical Association tells the Times of India. “When the $60 billion worth of patents expire … Indian companies will be able to capture a major chunk of the market.”

In fact, Indian pharma firms are gathering over the weekend to discuss how they plan to do that. One strategy has to be hooking up with multinational drugmakers. After all, Pfizer, GlaxoSmithKline, Daiichi Sankyo and now AstraZeneca have forged ties in India for that very reason: To gain access to that generics capability and the attached sales-and-distribution networks. It may just be that when Indian drugmakers capture a share of the off-patent market, they’ll be bringing Big Pharma along, too.

Source:

Popularity: 1% [?]

Eli Lilly executives said there’s every reason to be optimistic about future sales of Effient, the blood thinner launched last summer with expectations of perhaps growing to become a billion-dollar seller one day. The only worry seems to be early sales of the drug are headed in the wrong direction.

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Reporting its fourth-quarter results, Lilly said that sales of Effient, which the company co-markets with Japan’s Daiichi Sankyo, slid to a tiny $3.8 million world-wide in the fourth quarter. In the third quarter following the drug’s August launch, world-wide sales totaled $22.6 million.

On the conference call with analysts, Lilly execs said they were undeterred about Effient’s prospects, offering comments like “we feel just as good about Effient today as we did when we launched the product.” CEO John Lechleiter explained it was still early days in the roll-out and noted there was an initial jump in third-quarter sales because wholesalers were stocking up on the drug.

Lilly has long had high hopes for Effient to help replace the revenue from drugs that are losing patent protection in the next few years. But Effient also is in a tough market, competing against Plavix whose fourth-quarter sales rose 10% to $1.6 billion, Bristol-Myers reported today.

There was some better fourth-quarter numbers in Lilly’s results today and Lilly and Bristol-Myers also announced a settlement in a fight stemming from Lilly purchase of Imclone in 2008. Here’s the Dow Jones Newswires report with more details.

Source: The Wall Street Journal

Popularity: 3% [?]

What kind of company gets a drug through the FDA? If you’re a Japanese company, it seems to help if your main business isn’t prescription pharmaceuticals.

Perusing the list of FDA new drug approvals from Washington Analysis, we found four that originated in the labs of Japanese companies. A new drug for gout came from Teijin, a major textile maker. (Teijin licensed U.S. rights to Takeda.)

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The Otsuka group of companies, best known in some circles as the maker of the Pocari Sweat sports drink, came up with approval for a niche product for certain patients with low sodium levels in plasma.

Then there’s Kowa, which won approval for a cholesterol-lowering statin called Livalo. We’re somewhat at a loss to describe its core business. Its Web site mentions professional broadcasting equipment, apparel, textiles, home fashion, “bioarchitectural research” and a few other areas in addition to medicines.

Less successful at getting drugs through the FDA were the pharmaceutical giants that spend billions of dollars each year for precisely that purpose. Pfizer and Merck were among the big names that struck out for the year. That’s food for thought as the pharma industry tries to survive a wave of patent expirations and growth in U.S. prescription-drug spending slows sharply.

To be sure, some of the bigger names did get new drugs through the FDA in 2009, including Tokyo’s Daiichi-Sankyo, which won approval for the clot-buster Effient (co-marketed with Eli Lilly).

Source: The Wall Street Journal

Popularity: 3% [?]

The FDA approved 26 new drugs last year, edging out the 25 approvals for first-of-a-kind therapies in 2008, according to analysts at Washington Analysis. But biotechnology emerges as the real winner in the annual statistical review. Of the 26 new drug approvals in 2009, seven were for biotech therapies. That compares to four new biotech drugs in 2008 and two new sanctions in 2007.

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The Wall Street Journal asked Ira Loss, a senior health policy analyst at Washington Analysis, whether the spike represents a watershed of sorts for biotech drugs versus the small-molecule drug field. But he was a tad skeptical.

“I think it has the potential to be a breakout,” he responded, “but I am not prepared to say so based on one year. If there is a repeat performance in 2010 then I would be prepared to say the long awaited breakthrough in therapeutic biotech approvals may in fact be here. But not yet!”

The slow pace of drug approvals overall has bedeviled the biopharma industry for years. But with the Obama administration dedicating more money to the FDA, it’s quite possible that the routine breach of PDUFA deadlines can be rectified. With fewer regulatory delays at the agency, more approvals are almost a sure thing. That would be a big boon for biotech drugs and small-molecule therapies alike.

Among the potential blockbusters approved by the FDA last year: Eli Lilly’s and Daiichi Sankyo’s blood thinner Effient and Sanofi-Aventis’ Multaq. Amgen’s D-mab and Liraglutide from Novo Nordisk, meanwhile, are still on hold long after approvals were expected.

Source: FierceBiotech

Popularity: 3% [?]

Lots of big drug makers have been pushing into China lately. Eli Lilly’s adding jobs there even as it makes cuts in the U.S.; Novartis is spending $1 billion to expand an R&D facility in Shanghai; and Pfizer has made a couple deals to study and sell drugs in China.

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But at least one drug maker is moving in the other direction: Ranbaxy, the big Indian generics shop, said it’s getting out of a joint venture with a state-owned company to manufacture drugs in China. The partnership, established 16 years ago, was one of the first Sino-Indian joint ventures, the Financial Times notes.

Ranbaxy will still sell drugs in China, but the company is consolidating manufacturing as part of a series of cost-cutting measures. The company has also cut staff in some markets, Dow Jones Newswires says.

Last year, the Japanese drug maker Daiichi Sankyo bought a controlling share in Ranbaxy, shortly before Ranbaxy ran into trouble with the FDA. Daiichi Sankyo took a write-down of nearly $4 billion on the deal.

Source: The Wall Street Journal

Popularity: 2% [?]

Sweden’s BioInvent International has inked a license and discovery agreement with Japanese drugmaker Daiichi Sankyo to develop therapeutic antibodies against multiple targets.

Under the terms of the agreement, Daiichi Sankyo, which will fund all research work, will have access to BioInvent’s discovery and development technology platform and in-house antibody expertise. BioInvent, which has therapeutic antibodies to treat thrombosis, atherosclerosis and cancer in preclinical and clinical development, will secure certain co-promotion rights in Scandinavia and Baltic countries.

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BioInvent also will receive fees for its antibody library, as well as success-based milestone payments. It also is entitled to royalties on any commercialized products and will have the opportunity for selective co-promotion.

“We are pleased that our technology platform and expertise continue to attract the attention and long term commitment of big pharma.” BioInvent President and CEO Svein Mathisen says in a statement. “BioInvent is established as a trusted partner for the discovery and development of therapeutic antibodies, and with this agreement we are continuing to grow our presence and recognition in the Japanese market.”

Source: FierceBiotech

Popularity: 2% [?]

Ranbaxy Laboratories counsels patience. The Indian drugmaker, which has been negotiating with FDA over manufacturing problems since last year, says discussions with the agency are still in process. “Issues with the USFDA will take long and cannot be resolved in a day,” CEO Atul Sobti told reporters at the India Economic Summit (as quoted by the Economic Times).

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Predictably, the company’s shares dropped on Sobti’s comment. After all, some 30 Ranbaxy drugs were banned after FDA inspectors uncovered irregularities at two India manufacturing plants. And after that, the agency stopped even considering approval applications for drugs slated to be made at its Paonta Sahib plant.

Also predictably, Ranbaxy’s U.S. sales have fallen preciptiously since the ban, to $44 million in the third quarter. That’s a drop of 53 percent year over year.

Thankfully, Ranbaxy has its new parent company, Japan’s Daiichi Sankyo. Together with Daiichi, Ranbaxy has been making progress in markets outside the U.S. It’s getting ready to launch Eli Lilly’s osteoporosis drug Evista in Romania, under Daiichi’s European license for that drug. It’s planning to introduce Daiichi’s blood pressure med Olvance in India. In fact, Ranbaxy is working with Daiichi on a three-year growth plan, the Wall Street Journal reports. “It’ll be a comprehensive arrangement, which will cover manufacturing and even new chemical entities, Sobti told the Journal. So stay tuned.

Source: FiercePharma

Popularity: 3% [?]