Genzyme has reportedly started talks with the Japanese drug maker Takeda Pharmaceutical to try to sell itself for more than $18.5 billion or $82 per share, according to a few media reports.

Takeda is one of several pharmaceutical companies  approached by Genzyme CEO Henri Termeer,? who has been fending French drugmaker Sanofi-Aventis’  tender offer of $69 to acquire  Genzyme.

However, Mihoko Shinomiya, a spokeswoman for Osaka, Japan-based Takeda, declined to comment on the report, saying the company doesn’t respond to market speculation. Previously Takeda showed little interest in the rare disease field in which Genzyme works. Takeda acquired Millennium’s oncology pipeline when it bought out that developer for $8.8 billion. Since then, the company has spotlighted cancer, CNS diseases and metabolic diseases as its three key focuses. But with generic competition growing for key assets, Takeda has to move quickly to garner fresh revenue sources.

“Genzyme has been apparently talking to different companies to find better match/price and/or force Sanofi to get serious,” Michael Obuchowski, chief investment officer at First Empire Asset Management, writes in a message to Bloomberg. “Buying Genzyme would make sense for Takeda. Takeda has been trying to aggressively grow their U.S. business.”

Quoting sources, Dow Jones reported that Takeda did explore a takeover attempt, but isn’t likely to follow-up. Genzyme made it clear earlier that it is checking out all its options. However, in the months following Sanofi’s low-ball offer, no white knight has appeared to contest a takeover. That’s bad news for Genzyme, which desperately wants to get the bidding to the $80 mark and earlier estimated its own value at $89 a share.

Actos’ safety will be reviewed

The FDA announced that it has begun a safety review of the type 2 diabetes drug Actos (pioglitazone), after receiving preliminary results from a long-term study designed to gauge the risk of bladder cancer associated with use of the drug.

Early results of the study showed no overall association between Actos and the risk of bladder cancer. But, there was an increased risk of bladder cancer in patients with the longest exposure to Actos and in those with the highest cumulative dose of the drug, the FDA said.

The preliminary results are based on five years of data from an ongoing, 10-year observational study by the drug’s manufacturer, Takeda. The FDA stressed that it has not concluded that Actos increases the risk of bladder cancer. Patients should talk to their health-care provider if they have concerns about Actos, but should not stop taking the drug unless told to do so by their health-care professional, the agency said.

Actos is in the same class of drugs as GlaxoSmithKline PLC’s Avandia, which has not been associated with bladder cancer but has been linked to heart risks in some studies.

Actos is the Japanese drugmaker’s top-selling product with sales of about $4 billion a year, but the pill is due to face generic competition after it loses U.S. patent protection in January 2011.

Takeda said the results were early, and the company was committed to completing the 10-year study to get a better picture of bladder cancer rates.

“Looking at the completion of the study will give us the most accurate look at that,” Dr. Robert Spanheimer, Takeda medical director for Actos, said in an interview.

Orexigen has finally signed a deal with Takeda on its obesity drug Contrave The deal involved a relatively small upfront payment $50 million and more than a billion dollars in potential milestones 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 is similar to the agreement rival Arena 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.”

Faced with the looming loss of patent protection on Actos, the world’s top-selling diabetes drug, Japan’s Takeda has mapped out a drug development strategy that relies heavily on a new generation of therapies for “lifestyle diseases.” And with the ranks of the world’s overweight adults projected to grow 75 percent in the next five years, Takeda’s top planning honcho tells Bloomberg that he sees plenty of fresh opportunity for new and better therapies that deal with the health consequences of obesity.

Takeda’s best near-term pipeline program is a blood pressure drug–azilsartan medoxomil–now before the FDA. Alogliptin, a new diabetes therapy that could make it to the market by 2012 after meeting the FDA’s demand for a new trial, figures prominently in Takeda’s development schedule. TAK-875 is one step back in mid-stage studies for diabetes and there’s a promising obesity drug the Japanese pharma company licensed from Amylin in a $1 billion pact that’s also in Phase II.

“Lifestyle diseases are still an unmet medical need,” Masato Iwasaki, the head of Takeda’s planning ops, told Bloomberg. So are cancer and brain disorders, which also figure prominently in the pharma company’s future. The Actos franchise crumbles in January, leaving Takeda with a very narrow margin for error as it pushes ahead in the clinic.

Takeda also isn’t restricting itself to its slate of ongoing pipeline projects. The company reportedly told a Japanese newspaper back in early July that it would add more than $1.5 billion in fresh capital to fund new acquisitions. While obesity represents a tempting target, it’s also an enormously risky field. No new obesity drugs have been approved in the past decade.

Japan’s Takeda Pharmaceuticals says it will set aside more than $1.5 billion over the next three years to buy new products. That money will be in addition to the pharma company’s regular budget for new drug acquisitions. Yomiuri first reported the news. Report

California, USA-based Affymax has received $30 million in development milestone payments from Japan’s largest drugmaker, Takeda Pharmaceutical, as part of the companies’ exclusive global agreement to develop and commercialize Hematide (peginesatide), the US firm’s investigational drug for the treatment of anemia in chronic renal failure patients.

The payments were triggered by the achievement of database lock in the PEARL and EMERALD Phase III clinical trials, which evaluated Hematide to treat anemia in chronic renal failure patients.

Affymax and Takeda are collaborating on the development of Hematide and will co-commercialize the product in the USA upon approval. Takeda holds an exclusive license to develop and commercialize Hematide elsewhere, including Japan.

Under the terms of the agreement signed in 2006, which was established with an upfront fee of $122.0 million, the US company is eligible to receive up to $345.0 million in developmental and regulatory milestones. In addition, Affymax will be paid $150.0 million if the drug is successfully commercialized.

Affymax plunges on anemia drug trial results

However, ahead of the milestone news, Affymax shares plummeted a whopping 65% to $8.13, after the company announced what were viewed as disappointing Phase III results for Hematide. It said that, while Hematide proved as effective as currently prescribed drugs at treating anemia in patients with chronic kidney failure, a subgroup of patients who were not on dialysis experienced more heart-related side effects primarily driven by higher rates of death, unstable angina and irregular heart rhythm.

Raj Mehra of Auriga Securities downgraded the shares to hold from buy on Monday morning, saying that “the released data certainly puts the approval of Hematide in doubt at the moment, especially given the fact that US biotech major Amgen’s Epogen and Aranesp have adequately addressed the needs of the patients over the years.”

Affymax says that a slate of four late-stage trials for its anemia drug Hematide demonstrated that the therapy is non-inferior to Amgen’s Epogen and Aranesp, hitting its primary endpoints and putting it on a path to file for an FDA approval. But a stumble on cardio risks in a key sub-group of patients captured the unwelcome attention of analysts, with AFFY shares plunging 65 percent this morning.

Altogether 2,609 patients were studied in the four late-stage studies in Europe and the U.S., with the Hematide group getting dosed once every four weeks. Patients taking Epogen and Aranesp received their regular, more frequent, dosages. Takeda partnered on the rights to the therapy back in 2006, paying $105 million upfront with $430 million in potential milestones.

“Completion of these four Phase III studies is a key milestone and we look forward to pre-NDA discussions with the FDA,” said Arlene M. Morris, chief executive officer of Affymax, Inc. “We are continuing to evaluate the data, in particular the non-dialysis studies, and the impact on the timing of an NDA submission.”

But in a sub-group of pre-dialysis patients, Hematide was linked to a statistically significant increase in cardiovascular events, something Piper Jaffray felt could prevent an FDA approval in that patient group while possibly forcing a delay in regulatory filings for dialysis patients as well. Piper Jaffray downgraded Affymax stock from Overweight to Underweight.

Aaron Reames from Wachovia concluded that the safety data was a “major concern,” raising the prospect that the FDA would require another clinical trial ahead of any approval. And J.P. Morgan’s Geoffrey Meacham said that the bad news for Affymax was a plus for Amgen, which had been bracing for new competition.

- check out the release on the Phase III data
- here’s the report from the StreetInsider on Piper Jaffray
- here’s the article from Bloomberg

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