Orexigen has finally inked a deal on its weight-loss drug Contrave, accepting a relatively small $50 million upfront payment and more than a billion dollars in potential milestones from Japan’s Takeda in exchange for North American marketing rights for a therapy that’s about four months away from the FDA’s finish line.

Orexigen’s deal, which bears a close resemblance to the pact rival Arena Pharmaceuticals inked with Eisai for its experimental weight drug, leaves the biotech with co-promotion rights in the big U.S. market. There hasn’t been a new obesity drug approved in the U.S. in more than a decade. And with the obesity epidemic tipping scales throughout the market, any approved drug could achieve blockbuster status.

So far, though, none of the three contenders, which includes Vivus, has been able to get a blockbuster-sized upfront check–a sign of the serious concerns about potential safety issues at the agency. That leaves much of these deals back-ended, built around milestones and the tiered double-digit royalty rate that Orexigen can earn from Takeda. Noticeably absent from the deal-making are the U.S. pharma companies, several of which have been badly burned by obesity drugs’ troubled safety record. Investors, however, were excited by the size of the pact, driving up Orexigen’s shares by 26 percent in early trading today.

The agency’s safety concerns were on full display during a recent FDA panel review of Vivus’s Qnexa, which was rejected by a majority of the agency’s experts ahead of the FDA’s final ruling. Orexigen now faces a panel review on December 7, with a final decision deadline of January 31. Contrave is a combination of naltrexone SR and bupropion SR.

“Contrave represents an important addition to Takeda’s cardiovascular and metabolic disease franchise and we look forward to partnering with Orexigen,” said Shinji Honda, the CEO of Takeda Pharmaceuticals North America. “Takeda has deep experience in providing important medicines to treat chronic disease and Contrave will help us provide a full spectrum of treatment to patients for the management of obesity.”

Source: FierceBiotech

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The analysts at Concept Capital did the math on this year’s decisions by FDA expert panels and reached the disturbing conclusion (for biotech execs, anyway) that the numbers clearly indicate that the panels are getting tougher.

On 23 tries related to new chemical entities and major new indications, developers won 12 votes in favor of recommendation–a 52 percent rate of approval. “The percentage of ‘yes’ recommendations is down significantly compared to 2009 and 2008, when 75 percent and 80 percent of drugs received positive recommendations,” Ramsey Baghdadi, an analyst with Concept Capital, tells Adam Feuerstein at TheStreet, which has the full story.

What’s behind the new level of intensified criticism? New rules require a review now for most new therapies, which is triggering more votes. And the analysts insist that tougher conflict-of-interest rules are forcing the agency to pick less experienced people for the panel. That could be bitter news for anyone up for a review. A negative vote can torpedo a new drug’s chances at the agency.

Source: FierceBiotech

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A study funded by Abbott Laboratories offered more detailed evidence that its weight-loss drug Meridia increases heart risks, prompting renewed calls by consumer advocates and others to pull the drug from the market.

Final data from the so-called SCOUT study, published on Wednesday, showed Meridia increases the risk of heart attacks and strokes in patients who already have heart disease. Patients taking the drug lost an average of 8.8 pounds (4 kg).

Patients given Meridia had a 16 percent increased risk of heart problems such as heart attack or stroke compared to those given a placebo, the study showed. There was no increased risk of death, although Meridia patients also saw an increase in blood pressure and heart rate, it said.

The findings come two weeks ahead of a U.S. Food and Drug Administration public hearing to discuss whether to take further action against the drug, which is already withdrawn in Europe.

“When you put those … things together, you have to wonder if the drug should be on the market any longer,” said Dr. Gregory Curfman, executive director of the New England Journal of Medicine, which published the study.

“That’s what you’re trying to prevent through weight loss. You’re trying to prevent people from having heart attacks, and here this drug caused more,” said Curfman, a cardiologist.

Preliminary results from Abbott’s study were initially disclosed to both U.S. and European health officials in late 2009 and led to Meridia’s removal from the European market.

At the same time, the FDA strengthened the drug’s warning about risks to patients with pre-existing cardiovascular disease and called for a public meeting with its outside advisers.

An FDA advisory panel is to meet on September 15 to discuss the drug.

NOT A BIG SELLER

Meridia is not a big seller for the Illinois-based drugmaker, but has drawn attention to the controversial area of prescription diet drugs ever since its U.S. approval in 1997. The company expects Meridia’s 2010 U.S. sales to be less than $30 million.

The trial looked at 10,744 overweight or obese patients who were at least 55 years old and had either heart disease, diabetes or both conditions. It ran from 2003 to March 2009.

Abbott has defended continued use of the drug in the United States, where two out of three people are overweight or obese. The company, along with the study’s authors, said Meridia should still be used, just not by people with heart problems.

Abbott spokesman Scott Davies said the company only studied the drug in riskier patients because regulators required it as a condition for approval, and that Meridia already clearly warns heart disease patients against using the drug.

“If you look at all of the data involved, in the approved patient population there is certainly a positive risk-benefit profile,” he said. Those who are obese with no heart problems and have not lost weight with diet and exercise are ideal candidates for the drug, also known as sibutramine, he said.

Consumer groups and an FDA whistle-blower have long called on FDA to pull Meridia, in part because so many people have undiagnosed heart disease and are at greater risk.

Public Citizen’s Health Research Group Director Sidney Wolfe said the journal’s detailed data shows the FDA should have acted long ago.

“FDA has unconscionably allowed this drug, which should not have been approved in the first place, to stay on the market,” said Wolfe, who petitioned the FDA for Meridia’s removal in 2002. “The agency appears immobilized to act against drugs that have no unique benefits but unique, serious dangers.”

The FDA denied his request, in part saying it would await the results from the SCOUT trial.

FDA spokeswoman Karen Riley said the FDA advisory panel would review the company’s latest analysis, among other information. “There’s going to be a lot more data than what’s being provided in the journal piece,” she added.

Source: Reuters

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Don’t pooh-pooh FDA’s warnings on marketing violations. That’s the message Baxter Healthcare got in a recent warning letter. As Pharmalot points out, the letter citing Baxter for mismarketing its lung drug Aralast not only demands that the company stop using the offending brochure, but requires Baxter, as a repeat offender, to come up with a plan to make sure its drug promos tell the truth.

“[S]ince we have cited you for similar violations in the recent past, we request a response in writing indicating what policies and procedures your firm intends to adopt to ensure your prescription drug promotion activities comply” with the law, wrote FDA’s Mary Malarkey, director of the Office of Compliance and Biologics Quality. Baxter also has to explain to FDA why it thinks those proposed changes would actually work.

The FDA has stepped up its oversight of drug-marketing materials, issuing 68 letters so far this year, compared with just 41 in 2009 and 21 in 2008. Plenty of reasons for this, not least of which is that the agency changed hands when the White House did. Eye on FDA recently reported that DDMAC, the agency’s marketing oversight arm, has staffed up, so more eyes are looking at more media.

Source: FiercePharma

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The FDA has asked AstraZeneca’s MedImmune for more data on motavizumab, a monoclonal antibody being considered to help prevent serious respiratory syncytial virus. The disease is a major cause of lower respiratory tract infection and hospital visits in infants and children. In the complete response letter, the agency said it would need data from an additional trial of the drug to support a satisfactory risk/benefit profile for which the prophylaxis indication is being requested.

“The company continues to believe in the clinical benefit of motavizumab, and it will conduct a complete review of the CRL, continue ongoing constructive dialogue with FDA as well as make a decision regarding next steps in due course,” MedImmune noted in a statement.

The FDA previously moved its decision date on the drug from from June 24 to Aug. 27. That adjustment followed a 14 to 3 vote by an FDA expert panel, which raised a red flag on data linking motavizumab to a higher number of allergic reactions. The panel also wondered whether motavizumab is more more effective than Synagis–which loses patent protection in 2015.

Source: FierceBiotech

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This year’s flu vaccine has some consumers worried. While it might protect them against a potentially deadly virus, could they end up with salmonella instead?

The answer is no, according to the Food and Drug Administration and vaccine manufacturers.

Flu vaccine is manufactured by growing virus in chicken eggs, and eggs are the source of a salmonella outbreak this summer that has been linked to nearly 1,470 illnesses and prompted a nationwide recall of more than 550 million eggs.

But the eggs used to make flu vaccine come from different farms than those sold to consumers as food. Considered an important part of the government’s arsenal against a flu pandemic, they’re also tested vigorously for pathogens, officials say.

Eggs used for vaccines are also fertilized, while those sold for eating are not. A “seed virus” is injected into eggs, which grows in the egg white and is later harvested for use in vaccine.

“The recent August 2010 salmonella outbreak in shell eggs for food consumption and subsequent recall does not affect 2010-2011 influenza virus vaccine production, safety or availability,” an FDA spokeswoman confirms in an email to the Health Blog.

Sanofi-Aventis, the largest supplier of flu vaccine in the U.S., has its own suppliers of eggs. “The companies that supply our eggs are exclusive to us and follow much higher levels of biosecurity than companies that supply table eggs,” Donna Cary, a Sanofi spokeswoman, tells the Health Blog in an email. “The network of farms which supply our eggs are inspected by us and continuously meet rigid guidelines under which the chickens & eggs are monitored for any illness.”

Moreover, steps in the manufacturing process would remove salmonella or other bacteria, Cary points out. Sanofi and the FDA also test every lot of vaccine before its release, she adds. “One of the tests is for sterility, to ensure the product is free from bacterial contamination,” she says.

Cary won’t disclose the locations of the farms, which she says are in “numerous geographical areas.” That confidentiality, she says, is “part of the biosecurity measures.”

Source: The Wall Street Journal

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Company claims French drug giant is significantly undervaluing its potential.

Genzyme’s board responded with obvious scorn as Sanofi-aventis ended press speculation and confirmed yesterday that it had made a nonbinding offer to acquire the firm for $18.5 billion in cash. Genzyme chairman and CEO Henri Termeer says his firm will not even consider the $69 per share proposal, which sanofi-aventis points out represents a 31% premium on Genzyme’s stock price prior to July 22. This was the day before rumors of a takeover bid first hit the headlines.

“The Genzyme board is not prepared to engage in merger negotiations with Sanofi based upon an opportunistic proposal with an unrealistic starting price that dramatically undervalues our company,” Termeer states in today’s letter to sanofi-aventis’ CEO Christopher Viehbacher.

Sanofi-aventis maintains it was forced to make its offer public because attempts to engage Genzyme’s management in merger discussions had previously failed. The $69 per share offer was first batted to Genzyme chiefs on July 29, but the latter’s shareholders have essentially been kept in the dark, Viehbacher suggested in his letter sent  to Termeer yesterday. “We are committed to a transaction with Genzyme, and, therefore, we feel we are left with no choice but to take our compelling proposal directly to your shareholders by making its terms public …. Your continued refusal to enter into constructive discussions will serve only to further delay the ability of your shareholders to receive the substantial value represented by our all-cash offer.”

Sanofi-aventis believes Genzyme has “underperformed its peers for a number of years”. In stressing that the latter “continues to face several significant and well-documented challenges” that will take three to four years to resolve, Viehbacher’s letter is undoubtedly referring to the continuing and well-documented financial backlash of last year’s contamination at Genzyme’s Allston Landing manufacturing plant for Cerezyme and Fabrazyme. “An acquisition by sanofi-aventis would not only position Genzyme to overcome these challenges quickly and successfully by applying sanofi-aventis’ global resources and expertise to help realize Genzyme’s business strategy, but also deliver near-term compelling value to Genzyme’s shareholders that takes into account the company’s future upside potential,” Viehbacher maintains.

In response, Genzyme claims progress with respect to getting Cerezyme and Fabrazyme manufacturing back on track has been encouraging. On reporting its second quarter 2010 results in July, the firm confirmed that production of Cerezyme had reached its historical average, and the Allston Landing facility had returned to full operation. Shipments of Cerezyme were therefore due to start increasing in August, which would allow patients to start upping their doses in September and return to normal dosing during the fourth quarter. Genzyme, in parallel, confirmed receipt of both FDA and EMA approval to use the new working cell bank for Fabrazyme production, although shipments of the drug were not expected to increase until the fourth quarter 2010. Two bioreactors at the new Framingham manufacturing facility are also now operational, and Fabrazyme engineering runs are planned for September. Genzyme said it expects the facility to achieve approval during late 2011.

The rapid dismissal of sanofi-aventis’ second attempt to initiate acquisition talks “should come as no surprise,” Termeer stresses. “Without exception, each member of the Genzyme board believes this is not the right time to sell the company, because your opportunistic takeover proposal does not begin to recognize the significant progress under way to rectify our manufacturing challenges or the potential for our new-product pipeline.”

In May Genzyme confirmed it would have to forfeit $175 million in profits under a consent decree to correct manufacturing quality violations at the Allston Landing manufacturing facility. The same month the company announced plans to effect a $2 billion stock buyback and in addition sell, spin-out, or facilitate a management buy-out of its genetic testing, diagnostic products, and pharmaceutical intermediates businesses.

Reporting its second quarter 2010 results in July the company confirmed that during the period shipments of Cerezyme could still only meet 50% of demand for the drug, while shipments of Fabrazyme reached only 30% of demand. As a result, Cerezyme sales were $138.7 million in the second quarter of 2010, down from $298.1 in the equivalent 2009 quarter. Sales of Fabrazyme were $39.5 million in the 2010 quarter, down from $134.3 million during the same three months of 2009.

When the results were released, Termeer admitted the period was “difficult”. However, he stressed, “We expect that increasing sales of these products combined with reductions in our operating costs will produce an increase in earnings during the second half of the year.”

Sanofi-aventis has a market capitalization of some $75 billion, with annual revenues of about $38 billion and annual EBITDA of $16 billion. Sanofi-aventis’ share price on the Euronext Paris exchange has remained relatively stable today, oscillating 1.5% around its price at close yesterday. The firm’s stock dipped within the first 15 minutes of the Euronext Paris market opening this morning, before climbing up 1.2% at lunchtime in France.

Source: GEN

Popularity: 1% [?]

Japanese drugmaker Eisai’s blood clot candidate E5555 may be able to reduce heart attacks, strokes and cardiovascular deaths without increased serious bleeding risks, researchers say.

Scientists evaluated E5555, a new protease-activated receptor 1 inhibitor, in two Phase II trials in Japanese patients to assess the drug’s safety and tolerability. The researchers also wanted to determine its effects on major adverse cardiac events (MACE) and platelet aggregation in acute coronary syndrome and coronary artery disease.

Principal investigator Professor Shinya Goto says the data indicate E5555 may have the potential to reduce MACE with no increase in serious bleeding events even with addition to standard care in both ACS and CAD patients. Although there was a numerical trend towards an increase in bleeding with ascending treatment dose of E5555, this was not statistically significant, according to a release.  The data were presented Monday at the European Society of Cardiology (ESC) Congress.

“From these results, PAR-1 receptor antagonism may be an attractive pathway in the treatment of atherothrombosis,” Goto says in a statement. ”But we need further adequately powered trials to determine the efficacy and safety of E5555.” He notes that E5555 is worth taking into Phase III studies, but adds he doesn’t  know if Eisai has such plans, Reuters reports. Eisai is one of a number of drugmakers trying to develop drugs to compete in a market dominated by Sanofi-Aventis and Bristol-Myers Squibb’s mega-blockbuster Plavix.

ALSO: Eisai has received notification from the FDA that the agency expects to complete priority review of the eribulin mesylate NDA for locally advanced or metastatic breast cancer on or before December 30, 2010, which is a three month extension from the original Prescription Drug User Fee Act action date of Sept. 30.

Source: FierceBiotech

Popularity: 1% [?]

Tekamlo is a single pill that contains both a direct renin inhibitor and a calcium channel blocker.

FDA approved Novartis’ Tekamlo™ tablets for the treatment of high blood pressure. Tekamlo is a single pill combining the direct renin inhibitor Tekturna® (aliskiren) with the calcium channel blocker amlodipine. It is approved as initial therapy for patients who are likely to need multiple drugs to achieve their blood pressure goals and as replacement therapy for patients whose blood pressure is not adequately controlled with either aliskiren or amlodipine alone.

“Single-pill combination therapies provide a convenient treatment option while supporting physicians in addressing the complex needs of patients,” says Alan H. Gradman, M.D., professor of medicine at Temple University School of Medicine. “This new single-pill combination demonstrated greater blood pressure reductions than either drug alone in clinical studies and therefore provides a new option to consider when choosing appropriate high blood pressure therapies.”

Tekamlo works to lower blood pressure in two ways. The Tekturna component targets the activity of the renin angiotensin aldosterone system (RAAS), a blood pressure regulator. Tekturna directly binds to and inhibits renin, an enzyme produced by the kidneys that starts a process that can make blood vessels narrow and lead to high blood pressure.

The calcium channel blocker amlodipine lowers blood pressure by relaxing the blood vessel walls through the inhibition of calcium. Both of these medicines enable blood to flow more easily, therefore lowering blood pressure. The blood pressure lowering effects of Tekamlo are largely attained within one to two weeks, according to Novartis.

FDA sanction of Tekamlo was based on clinical trial data involving more than 5,000 patients with mild-to-moderate high blood pressure. An eight-week, randomized, double-blind study showed that the combination of Tekturna and amlodipine resulted in decreases in systolic/diastolic blood pressure at trough of 14–17/9–11 mmHg, compared to 4–9/3–4 mmHg for Tekturna alone and 9–14/6–8 mmHg for amlodipine alone.

In two additional double-blind, active-controlled studies of similar design evaluating patients with moderate-to-severe high blood pressure (SBP 160–200 mmHg), Tekamlo demonstrated significantly greater reductions in systolic and diastolic blood pressures when compared to amlodipine alone. In one study of 443 patients, the systolic/diastolic treatment difference between Tekamlo and amlodipine was 5.2/3.8 mmHg at the primary endpoint of eight weeks. In the other study of 484 patients, the treatment difference between Tekamlo and amlodipine was 7.1/3.8 mmHg at endpoint.

Source: GEN

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New BLA is expected to be submitted in mid-2012.

FDA has sent Genentech a refuse to file (RTF) letter with regard to the BLA for accelerated approval of trastuzumab-DM1 (T-DM1) in metastatic breast cancer. The agency stated that the T-DM1 trials did not meet the standard for accelerated approval because all available treatment choices approved for metastatic breast cancer, regardless of Her2 status, had not been exhausted in the study population.

Genentech will continue with its ongoing Phase III trial, known as EMILIA, and expects to submit a new BLA in mid-2012. The EMILIA study compares T-DM1 to lapatinib in combination with capecitabine in people with advanced, Her2-positive breast cancer whose disease has worsened after receiving initial treatment.

The BLA submitted for T-DM1 in July 2010 requested accelerated approval based on the results of a single-arm Phase II study. It showed that T-DM1 shrank tumors in one-third of women with advanced Her2-positive breast cancer who had received on average of seven prior medicines including two Her2-targeted medicines.

T-DM1 consists of ImmunoGen’s DM1 cancer-cell killing agent attached to Genentech’s Her2-targeting antibody, trastuzumab, using ImmunoGen’s linker and methods of attachment. T-DM1 is in global development by Roche under a collaboration agreement between Genentech and ImmunoGen.

Source: GEN

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