Seattle Genetics is getting some new warnings, including one new language about a potentially deadly brain infection, put into the FDA-approved prescribing information of its lone marketed product.

The company (NASDAQ: SGEN) said today it is working on an update to the label for brentuximab vedotin (Adcetris), which will include a boxed warning about the risk of patients on the lymphoma drug getting a potentially fatal brain infection called progressive multifocal leukoencephalopathy (PML). Seattle Genetics’ original drug label, cleared by the FDA in August, said there had been a case of PML in clinical trials, but now that the drug has been used more widely on the market, Seattle Genetics discovered a second case last fall, and said today it has learned of a suspected third case of PML. That information is prompting new warning language that’s supposed to help doctors spot signs of PML.

Several new biotech drugs have been linked to cases of PML, including Roche and Biogen Idec’s hit lymphoma drug rituximab (Rituxan). The Seattle Genetics drug is designed to hit a different target on cancer cells, and it is approved for use in a couple of rare malignancies—Hodgkin’s disease and anaplastic large cell lymphoma. The new treatment has shown strong ability to shrink tumors in clinical trials in the majority of patients who have essentially run out of options, and it has beaten Wall Street’s initial sales expectations. Now Seattle Genetics is looking to expand use of the drug to larger groups of patients. One of those label-expansion studies showed that the new drug shouldn’t be used in combination with a chemotherapy agent known as bleomycin, because of an elevated rate of lung toxicity, so a warning about that is also being incorporated into the Adcetris label.

The bleomycin warning isn’t much of a concern, because even though it’s part of a typical chemo regimen, Adcetris was never approved to be used in combination with that drug, and researchers are hopeful that Adcetris might be able to replace bleomycin for use in some patients, because the new drug has a milder side effect profile when used on its own.

“Our first priority is patient safety. By developing these agreed upon label updates with the FDA regarding PML and the contraindication with bleomycin, we aim to heighten awareness among healthcare professionals in order to most safely treat their patients with Adcetris. Although PML in lymphoma patients can be caused by factors such as underlying disease and prior therapies that affect the immune system, a contributory role of Adcetris cannot be excluded,” said Tom Reynolds, the chief medical officer of Seattle Genetics, in a statement.

Previous studies have said patients with blood cancers have about a 0.07 percent chance (1 in 1,400) of getting PML. Seattle Genetics didn’t say what the ratio is for patients getting Adcetris, but it has had two confirmed cases, and one suspected case, out of more than 2,000 patients worldwide who have gotten the new drug.

Shares of Seattle Genetics fell about 6.3 percent to $17.28 at 10:14 am Eastern time.

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Weston, MA-based biotech Biogen Idec (NASDAQ:BIIB) and Elan, its Dublin-based partner, have asked U.S. and European health regulators to approve a new prescribing label for the companies’ multiple sclerosis drug natalizumab (Tysabri) in an effort to reduce the risk of a potentially lethal brain infection called progressive multifocal leukoencephalopathy (PLM) in patients who take the treatment, according to a press release. The requested prescribing label would include whether a patient who is being considered for natalizumab treatment has an anti-viral antibody whose presence is one of multiple factors that help doctors tell whether or she is at risk of developing PML.

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At least one more patient has been diagnosed with a rare, and potentially fatal brain infection after taking natalizumab (Tysabri), the hit drug for multiple sclerosis from Biogen Idec and Elan, according to Biogen CEO James Mullen.

There are now 28 confirmed cases of patients with progressive multifocal leukoencephalopathy (PML) as of the last count in mid-December. That’s one more case than I counted in a detailed summary of PML risk that we published on November 19. Mullen made his remarks in front of a group of investors today at a Goldman Sachs conference titled “Healthcare CEOs Unscripted: A View From the Top.”

Mullen talked about the hit drug’s difficult history with PML as part of a wide-ranging and candid conversation with Goldman analyst May-Kin Ho in New York. These were the first public remarks Mullen, 51, has made since the Cambridge, MA-based company (NASDAQ: BIIB) announced this week he is stepping down in June as CEO, after a decade at the helm. He offered his thoughts on how to mitigate the risk for multiple sclerosis patients, his reflections on what worked and what didn’t in the 2003 merger with San Diego-based Idec Pharmaceuticals, and how the industry needs to change its ways to keep innovation alive. Here are the highlights that I picked up from the webcast.

On how Biogen Idec plans to keep doctors, patients, and investors informed about PML risk:

Biogen Idec says it plans to offer monthly updates to physicians about the latest statistics on PML cases, and infection rates. It will also staff a hotline for physicians who want to gather detailed, updated information and context from the company’s medical staff. The company plans to lay out the numbers in a more detailed fashion, with rates on incidence of infection, numbers showing how long certain groups of patients have been on the drug, combined with data on how many total patients are receiving treatment. “That’s the best way for people to visualize what’s going on,” Mullen says.

“The whole communications strategy around that has been challenging,” Mullen said. “We’ve gotten lots of feedback. Pretty much whatever we’ve done, someone won’t like it.”

On why he’s leaving the company in June:

Mullen noted that the Tysabri risk-management situation has stabilized during the past year. A new patent that lasts until 2026 has extended the lifespan of pegylated interferon beta (Avonex) which may help it fend off cheaper “follow-on” biologic competitors. And the product pipeline looks encouraging as well, he said.

“There are a lot of good prospects out there for Tysabri, and there aren’t, if you will, a lot of huge, thorny issues to be wrestled to the ground here in the short term. It’s a good time for a transition.”

From a personal perspective, he added: “If you’re going to have a mid-life crisis, you can do one of two or three things, right? Sports cars I’m too big for. Mistresses are not approved at home. Maybe a career change is what’s in order. I decided to go with Number 3. I think it’s a good time, for, you know, a transition. We’ve also got a new chairman with Bill Young. We’ve got some new board members. We’ll have a few more new board members. It’s a good time for people to sort of re-think … Next Page »

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Few doctors knew much about a rare brain infection called PML back in 2005, when two patients on a hot new multiple sclerosis drug from Biogen Idec and Elan died from the side effect. The infection, at the time, was generally considered a death sentence. But now with three years of data from more than 60,000 patients worldwide who have taken natalizumab (Tysabri) under strict monitoring by physicians, a new picture is emerging that shows PML is still very much a serious threat, but that it isn’t nearly as deadly as first feared.

While each and every confirmed case of PML, known formally as progressive multifocal leukoencephalopathy, scares investors in Cambridge, MA-based Biogen (NASDAQ: BIIB) and Ireland-based Elan (NYSE: ELN), I sought to assemble a big picture view of exactly how deadly PML really is when I interviewed Al Sandrock last week. He’s the senior vice president of neurology R&D at Biogen, and an assistant clinical professor of neurology at Harvard Medical School.

Before diving too far into the numbers about the risk of Tysabri, a little background is required. This drug, an antibody treatment designed to block certain white blood cells that cause MS when they attack nerves, has a history of also making patients vulnerable to infection. Biogen and Elan yanked it off the market in February 2005 after two cases of the brain disease were confirmed among patients taking the drug; a month later, a third case was confirmed. But legions of patients still demanded the drug, considered to be the most effective medicine on the market at reducing the disabling nerve damage from multiple sclerosis flare-ups. The FDA allowed the drug to return to the market in July 2006 after determining its benefits outweighed the risks, but it also forced doctors into a strict monitoring program to keep an eye out for the early signs of PML.

This matters not just for doctors and patients, but for Biogen’s and Elan’s financial futures. The drug, Biogen’s fastest-growing product, generated $560 million in sales in the first nine months of this year. (The importance of this drug is one reason why investors get so ticked at Biogen when it isn’t exactly forthcoming about every newly diagnosed case, but that’s a bone to pick another day.)

When the drug came back on the market, its FDA-approved prescribing information contained a prominent warning that about 1 out of every 1,000 patients on the drug were likely to get PML. But that was really just a forecast, and the actual risk-benefit balance for this drug is really a moving target that shifts over time when a new case is confirmed. So I sought to build a simple chart when I spoke to Sandrock that provides a snapshot of PML cases in February 2005, when the drug was pulled off the market because of the PML risk, versus those confirmed as of yesterday. Here’s what I gathered:

The February 2005 figures came from clinical trial data and formed the foundation for the FDA-required warning of the 1-in-1,000 chance of getting PML. The more recent figures include all the experience of patients who have gotten the drug since it was returned to the market in July 2006. The thing that jumped out at me was the fact that only five of the 27 confirmed patients with PML have died—meaning that the current survival rate stands at over 80 percent.

That curious fact has been buried under a rash of scary headlines … Next Page »

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[Update: 10/23/09, 1:10 pm Eastern] Shares of Biogen Idec and its Irish partner Elan dropped this morning after European regulators said they are taking a new look at the risk and benefit of natalizumab (Tysabri) for multiple sclerosis, now that 23 patients on the drug have been diagnosed with a rare, potentially fatal brain infection called PML.

Cambridge, MA-based Biogen (NASDAQ: BIIB) fell 5.5 percent to $44.61 at 11 am Eastern time today, while Elan (NYSE: ELN) dropped 21 percent to $5.11. The European Medicines Agency said it has initiated the review to discuss any additional measures necessary to ensure the safety of natalizumab, according to a Reuters report.

The new report was bound to alarm some investors, because 23 cases of progressive multifocal encephalopathy, or PML, is significantly more than the tally of 13 cases the FDA counted last month. Cases of PML been adding up since the drug was re-introduced to the U.S. market in July 2006 after it was previously withdrawn because of the risk. Despite the chance of the infection, which the FDA pegged at about 1 in 1,000, patients have continued to seek out the treatment, which physicians say is the most effective therapy on the market for multiple sclerosis. (Natalizumab is also approved as a treatment for Crohn’s disease.) More than 46,200 people worldwide were taking the drug at the end of September, Biogen said earlier this week.

Biogen finance chief Paul Clancy told Dow Jones earlier this week that the company will discuss how to communicate the link between long-term use of the drug and increasing incidence of the dangerous side effect.

Regulators might choose to recommend that patients who take the drug for long periods of time take breaks, or “drug holidays,” said analyst Christopher Raymond of Robert W. Baird & Co., in a note to clients this morning. Since so many patients depend on the product to control their symptoms, it’s unlikely that regulators would force it off the market, he said.

“We deem it highly unlikely that either FDA or EMEA would pull Tysabri from the market,” Raymond said. “With PML risk well known, we think the most likely scenario would be additional labeling restrictions suggesting perhaps a drug holiday after an extended treatment period.”

[Updated comment from Biogen Idec.] There isn’t any data that suggests imposing a drug holiday would reduce the risk of patients getting PML, but there is data that shows symptoms of multiple sclerosis return quickly once patients quit taking natalizumab, says Biogen Idec spokeswoman Naomi Aoki. The company is talking with regulators about the best way to update the drug’s prescribing information to reflect the increased risk with extended usage, but even so, the incidence of PML still appears within the stated range of 1 in 1,000 patients, she says.

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Biogen Idec and Elan’s fast-growing multiple sclerosis drug, natalizumab (Tysabri), has been connected to 13 cases of a potentially fatal brain infection, according to an FDA notice reported on today by Bloomberg News.

Cases of progressive multifocal encephalopathy, or PML for short, have been adding up since the drug was re-introduced to the U.S. market in July 2006 after it was withdrawn because of the risk. Despite the chance of infection, which the FDA pegged at about 1 in 1,000, patients have continued to seek out the treatment, which physicians say is the most effective therapy on the market for multiple sclerosis. More than 40,000 people worldwide were taking the drug at the end of March, according to Cambridge, MA-based Biogen (NASDAQ: BIIB).

Behind the scenes, researchers have intensified efforts to find out what it is about natalizumab that might be making people vulnerable to this particularly dangerous brain infection, and how to treat it. One Harvard Medical School neurologist, Igor Koralnik, presented research last week at at a European medical meeting that suggested patients’ immune system T cells didn’t work as well against the virus linked to PML when they were on the MS treatment, according to a separate Bloomberg report. Biogen said the results weren’t definitive.

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Cambridge, MA drug giant Biogen Idec (NASDAQ:BIIB) and Hawthorne, NY-based Acorda Therapeutics (NASDAQ:ACOR) announced today that Biogen Idec has acquired the rights to develop and commercialize Acorda’s multiple sclerosis drug, Fampridine-SR, in markets outside the U.S. Acorda will receive an upfront payment of $110 million and additional payments of up to $400 million, and retains commercialization rights to Fampridine-SR in U.S. markets. The deal increases the Cambridge company’s MS drug footprint, which already includes Biogen drugs Avonex and Tysabri. The latter drug has come under scrutiny recently for its link to a severe brain infection called progressive multifocal leukoencephalopathy, or PML.

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Biogen Idec (NASDAQ:BIIB) reported a tenth case of a serious brain infection in a patient taking Tysabri, the Cambridge, MA-based company’s drug for multiple sclerosis and Crohn’s disease. The news was disclosed late last Friday on the company’s website (pdf here). Luke wrote back in December about the history of Tysabri, which was pulled from the market in February 2005 after two cases of PML and returned to the market under a strict monitoring program in July 2006.

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Biogen Idec is the world’s largest maker of multiple sclerosis drugs, and to keep it that way, the company needs to stay on the good side of neurologists. So when a large number of these docs get together for a scientific meeting, it’s time to start wooing.

This is at the top of Biogen’s agenda for the week ahead, as the American Academy of Neurology, the nation’s biggest group of doctors who treat multiple sclerosis, Alzheimer’s, Parkinson’s and other neurodegenerative diseases, is holding its annual meeting April 26 through May 1 in Seattle.

So before the wining and dining begins, I lined up an interview with Al Sandrock, Biogen’s senior vice president of neurology R&D, to talk about the key points the company will try to make to doctors. The company heads into this meeting with weakening demand, as natalizumab (Tysabri) produced $227 million in first-quarter sales, quite a bit short of Wall Street’s expectations of $246 million.

Biogen plans to keep natalizumab on center stage at the meeting. After all, it’s regarded by many as the most effective MS drug on the market, although it also carries the risk of subjecting patients to PML, a potentially fatal brain infection. On the other hand, Biogen also has plenty to say about another drug, an experimental version of its best-selling MS drug, interferon-beta (Avonex), that’s supposed to require fewer shots, and reduce flu-like side effects. The company also is preparing the first clinical trial of a drug designed to regenerate the myelin coating around nerves, which gets damaged by MS.

“Physicians and patients will be thrilled to see how large the MS pipeline is and how far we’ve come in the past 10 years,” Sandrock says.

Biogen’s head of drug safety, Carmen Bozic, is expected to give an overview of the risk/benefit balance for natalizumab. The drug’s prescribing information has stated that patients run a 1 in 1,000 risk of getting PML, ever since the drug was re-introduced to the market in July 2006. But Bozic’s presentation will point out that after almost three years on the market, there are now more than 40,000 patients taking the product, and there have been six confirmed cases of PML, Sandrock says. Five of the six patients diagnosed with PML since the drug returned to the market are still alive, said spokeswoman Shannon Altimari.

“When the drug was approved, it was said the risk of PML was 1 in 1,000, and it was fatal,” Sandrock says. “Now we can see the risk is likely less than 1 in 1,000, and PML is a more manageable than we thought. We think physicians will draw some comfort from that.”

The company will also show data from a Phase I trial of its pegylated interferon-beta1a. This is the drug that Biogen is counting on will extend the life … Next Page »

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A patient taking Biogen Idec’s fastest-growing multiple sclerosis drug has died from a rare brain infection. The patient, a woman in the U.S., was diagnosed in October with the PML brain infection after taking natalizumab (Tysabri) for her neurodegenerative disease, said Naomi Aoki, a spokeswoman for the Cambridge, MA-based biotech company.

The death represents the first fatality from PML (progressive multifocal leukoencephalopathy) for a patient taking the drug since it was re-introduced to the market in July 2006, Aoki says. But it’s not an isolated case. Two patients in Europe were diagnosed with the infection in late July, and another European patient was diagnosed earlier this week. The two people who got the brain infection in July are still alive, and “have seen improvement,” Aoki says.

The product, an antibody drug designed to block cells of the immune system from attacking otherwise healthy nerves, has a history of also making patients susceptible to infection. Biogen Idec (NASDAQ: BIIB) and its partner, Irish drugmaker Elan, yanked it off the market in February 2005 after two cases of the brain disease were confirmed among patients taking the drug; a month later, a third case was confirmed. The FDA allowed natalizumab to return to the market in July 2006 after determining the drug’s benefits outweighed the risks, since it is the most effective medicine yet at reducing the risk of multiple sclerosis flare-ups. It is administered now under a strict patient monitoring system that looks for signs of PML.

By the end of September, the drug was being taken by more than 35,000 patients worldwide, and it is Biogen’s fastest-growing product. Since 2006, the prescribing information included with the drug has stated that about one in 1,000 patients who take Tysabri run the risk of getting PML.

So it may not be a surprise that a patient died—but any news of this death could still be harmful to Biogen, said Christopher James, an analyst with Rodman & Renshaw in New York, in a note to clients today. After the news, shares of Biogen Idec dropped 2.3 percent to $46.88 at 1:22 pm Eastern time today.

“Given the expected negative attention that this death will attract in the medical literature and media, we believe there is an increased risk to owning shares of both Biogen Idec and Elan,” James said.

The patient’s medical history will surely be analyzed and discussed by doctors seeking ways to best manage PML. The patient had taken 14 infusions of natalizumab over a little more than a year before she was diagnosed with the disease, as I reported back in October. About 18,000 patients have taken Tysabri for more than a year, 9,500 have been on the medicine for more than 18 months, and 3,700 have been using it for two years or more, James said. Based on those numbers, “we believe the risk of PML remains below the rate of 1 in 1,000 indicated in the label.”

He predicts the drug will generate $1.8 billion in worldwide sales in 2012.

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Biogen Idec (NASDAQ: BIIB) said today that a patient has been diagnosed with a rare, and often fatal brain infection called PML while taking natalizumab (Tysabri). The Cambridge, MA-based biotech company, which markets the drug along with its partner, Ireland-based Elan, said the patient was in Europe, has a history of taking other immune-suppressors for multiple sclerosis, and had been on Tysabri for more than two years. The patient is being monitored.

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The most effective drug on the market today for patients with multiple sclerosis has roots in a dingy old lab in the 1980s on Seattle’s First Hill. It was there that a pair of young scientists at the Fred Hutchinson Cancer Research Center, Bill Carter and Elizabeth Wayner, made key discoveries that paved the way for natalizumab (Tysabri).

The treatment has become the fastest-growing product for Cambridge, MA-based Biogen Idec (NASDAQ: BIIB) and its Irish partner Elan (NYSE: ELN), and it’s projected to generate $1.6 billion in sales in 2011. Most people know of its link to a rare, often fatal brain infection called PML, and its dramatic recovery. But few people know where the drug comes from. So I stopped by Carter’s new lab at the South Lake Union campus of “The Hutch” to hear the story.

Carter, 62, didn’t seem the least bit self-important about this discovery when I stopped by his office last week. He wore a brown T-shirt and brown sandals. Manila file folders with scientific papers were stacked high on the shelves in his office. He didn’t care much to discuss the financial and legal aspects of this story, but when the subject turned to the science, Carter’s eyes lit up with boyish enthusiasm.

He got his doctorate at the University of California-Davis in 1974, where he studied how cells bind to each other, or cell adhesion. After a yearlong fellowship in Israel, he joined the Hutch as a postdoc, shortly after it was founded in 1975. Specifically, he wanted to learn more about the adhesion properties of epithelial cells, those that form linings or boundaries between tissues like skin or other organs. He was interested in these cells because they are involved in most adult cancers.

Those cells remain in a non-active state most of the time, but can become highly activated in the case of an injury, Carter says. For example, when a person falls off a bicycle and scrapes a knee, these epithelial cells leap into action. The cells work to close the wound, secrete proteins that trigger an immune system reaction that mop up all the foreign invaders like bacteria. Other cells, platelets, pour in to the area to form clots.

“Everything is moving in that area to cope with disaster,” Carter says.

This whole process requires big-time changes in cell adhesion properties. By the early to late 1980s, when Carter was pursuing this work on the third floor of Eklind Hall (an old building on Seattle’s First Hill that Xconomy Seattle proudly calls home today), scientists knew very little about this cell adhesion process or the proteins on the surface of cells. “None of the components were known,” Carter says.

One way to identify these components was to develop targeted antibodies that would bind with and block receptors on cells. Carter and his colleagues found GP-140, a new type of protein. This was important because it led to the development of methods to identify more adhesion receptors on the surface of cells, and what they interact with. It was the spark that set Carter and his lab partner Elizabeth Wayner off to the races for the next five years. “We said let’s hunt for different adhesion receptors” on cells, which could serve as new antibody drug targets.

Wayner was one of the scientists who came into Carter’s lab as an immunology postdoc. The biggest step ahead for these two was when they made antibodies that identified a new cell surface receptor called alpha4 beta1. Wayner and Carter, in a paper in 1989 in the Journal of Cell Biology, identified one antibody in particular called P4C2 that they said “completely inhibited” binding to this target. It’s now the target—today called an integrin—which is hit by the natalizumab (Tysabri) antibody.

Carter and Wayner’s work later veered in different directions. … Next Page »

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Tysabri has been linked to its first U.S. case of an often-deadly brain infection since it was re-introduced to the domestic market two years ago. Cambridge, MA-based Biogen Idec (NASDAQ: BIIB) and its partner Elan said today they have notified regulators that a rare brain infection called PML has been diagnosed in a patient with multiple sclerosis, according to a regulatory filing.

The patient, a woman, has a history of taking other immune-suppressing drugs for MS, including beta-interferons, and methotrexate for a rheumatology condition, Biogen said. The infection was diagnosed early based on a doctor’s observation of possible symptoms, an MRI scan, and an examination of spinal fluid. The patient, who had taken 14 infusions of Tysabri over a little more than a year, is being treated by her physician, said company spokeswoman Naomi Aoki.

Tysabri is under intense scrutiny for its link to PML, since it was pulled off the market in February 2005 after doctors discovered two cases of the rare infection, which can be deadly. The FDA allowed Tysabri back to the U.S. market in July 2006 after deciding that the benefit of the drug-the most effective yet against MS-was worth the risk. The drug was brought back under a strict patient monitoring program called TOUCH. No new cases of the infection had been reported until this past July, when Biogen and Elan disclosed that two patients in Europe had been diagnosed. Since then, the first patient, who was described as remaining able to walk and live at home, has “continued to improve,” Aoki says. The second patient who was hospitalized remains in the hospital, but has also made improvement, Aoki says.

More than 35,000 patients worldwide were taking Tysabri as of the end of September, so three cases is well within the warning in the drug’s label that the chances of getting PML are about 1 case in 1,000. Two analysts who sent me their notes, Christopher Raymond of Robert W. Baird and Christopher James of Rodman & Renshaw, didn’t seem alarmed by the new case. Raymond said he still expects Tysabri to generate $1.6 billion in annual sales in 2011.

“Although the headline of a new PML case is never good for the stock, given the slowdown in patient additions highlighted by management on its third quarter conference call, we believe physicians may already be reacting to this reality,” of new PML cases, Raymond said.

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Biogen Idec has turned down the requests of the family and high-profile friends of a dying patient at the Mayo Clinic to provide an emergency dose of Tysabri to try to combat the man’s cancer—an unapproved use of the drug. It’s a vivid example of the ethically treacherous zone that companies must traverse when patients request access to their drugs before they are approved as safe and effective by the FDA.

The case of Frederick Baron hit the blogosphere in a open letter to Biogen CEO James Mullen posted this morning by Baron’s son, Andrew. The letter grabbed instant attention (including from TechCrunch’s Michael Arrington, who wrote a scathing post about Biogen’s refusal), in part because Andrew Baron, CEO of RocketBoom, noted that celebrities including Lance Armstrong, former President Bill Clinton, U.S. Senators Ted Kennedy and John Kerry, among others, all personally called on Biogen to clear the way for their friend to get an emergency dose of Tysabri. Frederick Baron, 61, a famous trial attorney and prominent Democratic fund-raiser, has multiple myeloma, a deadly cancer of the bone marrow; Tysabri is only approved by the FDA for the treatment of multiple sclerosis and Crohn’s disease.

Normally, with a marketed drug like Tysabri, physicians like those at the Mayo Clinic in Rochester, MN, are free to prescribe it for any disease, or any dose, however they see fit, under what is known as “off-label” use. The situation is more complicated with Tysabri, because it is currently available only under a strict prescribing and monitoring program called Touch; the program was instituted when Tysabri was brought back to the market in July 2006 after having been withdrawn in 2005 because of its link to a rare and often fatal brain infection called PML. Tysabri is now taken by an estimated 32,000 patients worldwide with multiple sclerosis and Crohn’s disease.

Frederick Baron’s physician hit upon the idea of treating him with Tysabri because samples of his cancer cells turned out to carry a molecular marker that Tysabri, an antibody drug, is designed to seek out and block, according to Andrew Baron’s letter. Biogen has done some animal tests that suggest Tysabri might be an effective treatment for multiple myeloma, and in fact, it began treating the first patient in a clinical trial of Tysabri against the condition last month, says company spokeswoman Naomi Aoki. Frederick Baron’s physician is an investigator on this study and well-familiar with its rules, but Baron isn’t eligible to participate in the trial because he is too sick, Aoki says.

In his letter, Andrew Baron wrote that FDA commissioner Andrew von Eschenbach “has granted special approval” for his father to receive Tysabri, which essentially puts the ball in Biogen’s court. Under FDA rules, the company has discretion to give out the drug for such unapproved uses—what is known as “emergency use” or “compassionate use”—but it chose not to, Aoki says. If something went wrong in an uncontrolled setting, it might lead to further restrictions on the drug’s use among existing patients with MS and Crohn’s disease, she says.

“We concluded when we re-introduced Tysabri that we cannot make it available for uses other than the FDA-approved use, or for an FDA-approved clinical trial,” Aoki says.

Still, I asked if this was a difficult decision, given the life and death nature of the matter. Andrew Baron’s letter says his father may have only a day or two left to live. “Of course, it’s a difficult decision for us. Our thoughts go out to the family. We don’t take this lightly, but we feel we have a responsibility to protect patients already on this drug who are benefiting from this drug,” Aoki says.

When asked if legal liability is part of the company’s concern, Aoki referred back to her statement about protecting the interests of patients already on the drug.

This sort of ethical quandary has come up for other companies, most recently Plainfield, NJ-based PTC Therapeutics, which has refused to give a boy with muscular dystrophy an experimental medicine outside of the protocol of a clinical trial.

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Cambridge, MA-based Biogen Idec and its Irish partner, Elan, said today they have started the first clinical trial of Tysabri as a cancer treatment. Tysabri, approved for multiple sclerosis and Crohn’s disease, is being studied initially in a trial of 12 patients with multiple myeloma, a deadly cancer of the bone marrow. The drug works by blocking the VLA4 protein, which is found on the surface of myeloma cells, the companies said in the statement. Tysabri suffered a setback this summer in multiple sclerosis, when two patients in Europe on the drug were diagnosed with PML, an often-fatal brain infection.

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Biogen Idec and Elan got clobbered by investors a few weeks ago when they reported that two new patients developed PML, the often-fatal brain infection, after taking Tysabri. But in an announcement about the cases on its website, the FDA doesn’t seem overly alarmed about the risk associated with drug for multiple sclerosis and Crohn’s disease from the Cambridge, MA-based biotech company (NASDAQ: BIIB) and its Irish partner (NYSE: ELN).

The FDA noted on its Web site this week what we’ve reported previously: that two patients in Europe who took Tysabri as a single agent for more than a year have been confirmed to have PML. The agency points out that 39,000 patients around the world are taking Tysabri, and 12,000 have been on it for more than a year. No new cases have been seen in the U.S., where about 7,500 patients have been taking the drug for more than a year, under a close patient monitoring program.

“While the two patients who developed PML were on monotherapy (taking the drug by itself, without other medicines), the FDA still believes that Tysabri monotherapy may confer a lower risk of PML than when Tysabri is used together with other immunomodulatory medicines,” the FDA said.

Since MS is an autoimmune disease in which the immune system attacks the coating around nerves, several drugs like Biogen’s Avonex work by blunting the immune system, which can make patients vulnerable to infections. Two previous cases of PML identified in February 2005 were among patients who took a combination of Tysabri and Avonex. That was scary enough at the time to get the companies to pull the drug off the market. The drug, now Biogen’s fastest-growing product, was reinstated by the FDA in July 2006 as patients clamored for it, saying the benefit of reducing MS flares was worth the risk.

The FDA noted that it is working with the companies to update Tysabri’s prescribing information, and pass the word on to doctors and patients. The agency has previously estimated the risk of getting PML at about 1 in 1,000 patients, and the drug hasn’t gotten close to exceeding that rate. If it does, then the FDA’s language will probably get a lot more stern.

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Abbie Celniker has been climbing biotech’s corporate ladder for much of her career. Higher and higher she went, in senior R&D jobs at Genentech, Wyeth Biopharma, Millennium Pharmaceuticals, and most recently as global head of Novartis Biologics in Cambridge, MA. Now, at 49, she has taken a detour to become CEO of a growing startup company in Cambridge called Taligen Therapeutics.

At big companies, the higher Celniker climbed, the further she got from her roots as a molecular biologist. “At a large pharma company, you’re managing or directing things at such a high level, you couldn’t really see things at a level where you’re exposed to the science anymore,” Celniker says. “I fell in love with the science they have here.”

Taligen, she explained to me recently, is developing drugs for inflammatory diseases that work in a new way, by controlling the “alternative pathway of complement”—a part of the immune system that helps initiate and amplify inflammation. The approach is different than that of other protein drugs that work further “downstream” in the chain of inflammatory events, like Amgen’s arthritis drug Enbrel or Biogen Idec and Elan’s multiple sclerosis and Crohn’s disease treatment, Tysabri, she says. Intervening earlier in the complicated cascade of events, the reasoning goes, could better control inflammation.

Whenever a drug sets out to tamp down an excessive immune reaction, though, researchers have to worry about going too far, and making the body vulnerable to infection. (Tysabri, for example, has been linked to a potentially fatal brain infection called PML.) Taligen’s drugs may have an advantage here, because they can be designed to work locally just at the organ or tissue affected by an inflammatory disease, rather than acting throughout the entire body. A drug for asthma, say, could be inhaled into the lungs, or a treatment for macular degeneration, the leading cause of blindness in the elderly, could be injected behind the eye, Celniker says.

Founded in 2004 by Woodruff Emlen and Michael Holers, professors at the University of Colorado, and working with a group of just seven people in discovery research, Taligen has built a suite of protein-based drug candidates that modify the amplification role of the alternative complement pathway. The work is still in early stages, and hasn’t yet progressed to clinical trials, yet it has attracted big money. Taligen announced in February that it had secured a $65 million Series B round of venture capital, divvied into undisclosed chunks based on hitting milestones in development. The first chunk arrived in January, led by Alta Partners and Clarus Ventures, and included existing investors Sanderlin Ventures, Tango and High Country Venture.

The cash is being used to double the size of the company, Celniker says. Taligen moved its corporate headquarters from Aurora, CO, to Cambridge last month when Celniker joined. While its discovery group will stay in Colorado, the company is looking for people in Cambridge with experience in animal testing, manufacturing for clinical trials, and early-stage development work, who are hard to find in Colorado, Celniker says. “It’s hard to build a company to make protein drugs if you’re not in the Bay Area or here,” she says. “We need people who have done it before.”

Celniker makes it sound like it won’t be too hard to find recruits. “Literally you can’t walk down the street without bumping into someone you want to consult with or hire,” she says. And at a company of Taligen’s size, Celniker will surely get to see those people, and the science they’re working on, at close range.

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Perhaps there was no way that Biogen Idec (NASDAQ:BIIB) would see a major drop in its stock price without activist investor Carl Icahn working his way into the storyline.

SEC documents filed Monday show that Icahn went on a Biogen stock-buying binge beginning on August 1, the day after Biogen and its partner, Ireland’s Elan, reported that two multiple sclerosis patients taking their drug Tysabri had developed the rare and often fatal brain infection progressive multifocal leukoencephalopathy, or PML. Between then and August 11, as Biogen’s stock plummeted more than 25 percent to a one-year low of $49.60, Icahn through various entities purchased about 5 million shares of Biogen common stock, upping his stake in the company from 4.3 percent to 6 percent in the process.

Icahn’s big stock grab could signal his continued interest in pushing for a sale of the Cambridge, MA, biotech firm, which was unable to find a buyer late last year after being pushed by its maverick investor into investigating a sale. In June, Biogen fended off an attempt by Icahn to win three board seats at the company’s annual meeting. Now, it seems apparent, the battle is far from over.

Biogen’s stock was up $0.72 (1.4 percent) this morning, at $51.47.

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Shareholders in Biogen Idec (NASDAQ: BIIB) and its partner Elan are getting pounded today. The Cambridge, MA-based biotech’s shares fell 25 percent, to $52.05 at 10:11 a.m. today after it reported two new cases of a rare, often fatal brain infection called PML, among patients taking its multiple-sclerosis drug Tysabri. Shares of Ireland-based Elan (NYSE: ELN) were hit even harder, down 45 percent to $11.10.

Analysts grilled this company this morning on a conference call about the cases, which we reported on yesterday. “We worry that this may be just the beginning of confirmed PML cases, possibly prompting some physicians to re-think this therapeutic option,” said Christopher Raymond, an analyst with Robert W. Baird in Chicago, in a note to clients before the call.

Biogen and Elan avoided any talk about long-term financial impact from the cases, so their forecast of getting 100,000 patients on the drug by the end of 2010 remains intact until further notice. The company has said that forecast always assumed some level of PML risk. “We believe Tysabri’s risk management profile continues to be favorable, offering new hope for patients,” said Cecil Pickett, Biogen’s president of research and development, on the call.

The association with PML has long dogged Tysabri. Biogen and Elan pulled the drug off the market in February 2005 after two cases of the brain disease were confirmed among patients taking the drug; a month later, a third case was confirmed. The FDA allowed Tysabri to return to the market in July 2006 after determining the drug’s benefits outweighed the risks, since it is the most effective medicine yet at reducing the risk of multiple sclerosis flare-ups. This January, the agency approved the drug for the treatment of Crohn’s disease as well. Tysabri’s prescribing information includes language stating that the risk of PML is at about 1 in 1,000 users.

The two new cases of PML were confirmed in patients in Europe, Biogen and Elan said. About 31,800 patients were taking Tysabri worldwide when Biogen reported earnings last week; 13,900 of them have been taking it for a year or more, and 6,600 have been on it for 18 months or more. One of the patients diagnosed with PML had been taking the drug for 17 months, the other had been on it 14 months. Biogen declined to speculate whether the risk of getting PML increases as patients remain on the drug for longer periods of time.

If patients are diagnosed with PML, doctors can perform a blood-exchange procedure to wash the Tysabri out of their system, which the companies described this spring in a presentation at the American Academy of Neurology meeting. Whether that really helps these two patients with PML will go a long way toward determining how big of an impact this news has on Tysabri’s future.

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Cambridge, MA-based Biogen Idec (NASDAQ: BIIB) and Ireland’s Elan reported some serious bad news this afternoon on their multiple sclerosis drug Tysabri. Two new patients taking the drug in Europe have developed the rare and often fatal brain infection progressive multifocal leukoencephalopathy, or PML, according to a regulatory filing with the Securities and Exchange Commission.

The filing says that one patient, in Europe, developed PML after taking Tysabri by itself for about 17 months. The patient has remained stable at home and able to walk, according to the statement. The second patient, who took Tysabri for 14 months after having taken other medicines for multiple sclerosis, is currently hospitalized, according to the company.

Tysabri has a painful history with PML. The drug was pulled from the market in February 2005 after doctors discovered two cases of the rare infection, which can be deadly. The FDA allowed Tysabri back to the market in July 2006 after deciding that the benefit of the drug—the most effective yet against MS—was worth the risk. As recently as last week, Biogen and Elan reported there were no new cases of PML since Tysabri was reintroduced with a strict monitoring program, and that 31,800 patients were taking it worldwide. The drug, Biogen’s fastest-growing product, is vital to the company’s financial future, and has been estimated to generate $2.8 billion in annual sales at current prices in 2010.

Biogen’s stock dropped 19 percent on the news at 5:58 p.m. Eastern time in after-hours trading to $56.56. The company is planning to have a conference call with investors at 8:30 a.m. Eastern time tomorrow morning.

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