The potentially fatal infection, known as progressive multiform leukoencephalopathy (PML), occurs in an estimated 1.5 per 1,000 patients treated with Tysabri during months 25 to 36, the Food and Drug Administration said.

The FDA said it was the first time it had estimated the chances of PML for specific time intervals rather than providing a cumulative risk over years.

Of those, 14 have died and 56 are alive with varying degrees of disability ranging from mild to severe. There were no additional deaths in October.

This brings the total number of patients found to have developed PML to 68 since the beginning of September. Deaths among patients who had developed PML rose by 2 to 14.

PML, progressive multifocal leukoencephalopathy, is a rare, always serious and often fatal disease that damages the white matter of the brain at multiple locations.  It is caused by the activation of the JC virus (which is normally present but kept under control by the immune system) by immmunosupressive drugs such as natalizumab (Tysabri).

Hard and fast data confirms that from July 2006 (when Tysabri marketing resumed) to September 8, 2009, thirteen worldwide cases of Tysabri-related PML occurred in patients being treated for MS with Tysabri monotherapy. Of these, only four cases were patients in the United States, according to an FDA Post-marketing Drug Safety report.

Germany is an important MS market for Biogen. Aside from the U.S., Europe is home to four of the top seven markets — Germany, Italy, UK, and Spain — in terms of commercial dollars spent on disease modifying drugs for use in MS, according to an analysis of the global MS market by the pharmaceutical research outfit Visiongain.

Patients receiving monthly Tysabri infusions in the U.S. must be enrolled in the TOUCH Distribution Program overseen by Biogen, which involves (i) extensive monitoring of all patients for signs of PML and (ii) education of all patients and providers, with strong emphasis communicated to all parties that the drug is contraindicated for use in MS patients taking any drugs that may increase their risk of opportunistic infections, including drugs that lower immune function (e.g., azathioprine, chemotherapy, cyclosporine) or immunomodulators, such as the interferon-based disease-modifying therapies.

Aside from voluntarily enrollment of patients in Biogen’s Phase 4 trial, TYGRIS (Tysabri Global Observation Program in Safety), which is a prospective 5-year, 5000-patient cohort observational study to further evaluate PML risk and overall safety of Tysabri therapy, there are few — if any — restricted distribution programs in place throughout Europe.

As mentioned, most of the other reported cases of PML are alleged to have occurred in Germany, where oversight is purportedly lax, especially in the monitoring of the presence of latent JC virus  and a mandated prior “washout” phase required in patients recently removed from other immunosuppressant therapies, both high-risk factors for development of PML. However, since late summer, German authorities have been working with the company to make sure “appropriate use of Tysabri is monitored and followed up with [patients],” Chief Executive Jim Mullen said on the third-quarter earnings call.

The duration of therapy in the newly diagnosed PML patients is unknown. That said, lax supervision in German — and other European — MS treatment facilities could be a contributing risk factor behind the higher incidence(s) and prevalence of reported PML cases.

In the last 12 months, Biogen has engineered relationships between academic reference centers and many of the larger MS clinics in Germany so that the prescribing of Tysabri can occur in a more structured environment — in compliance with a common protocol developed and published by the Medical Advisory Board of German MS, according to chief operating officer Robert Hamm. To date, 250 top German MS treatment centers are linked to 40 reference centers, he said on the call. This initiative should play out in the company’s favor as European regulators re-assess the risk-benefit profile of Tysabri.

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Two more cases of a rare brain infection have emerged in users of the multiple-sclerosis drug Tysabri, sold by Biogen Idec Inc. and Elan PLC, the first such incidences since Biogen stopped updating investors of the situation in July.

At that time, Biogen had confirmed 11 cases of progressive multifocal leukoencephalopathy, or PML, since the drug’s relaunch in July 2006; Tysabri was pulled from the U.S. market in 2005 because of PML concerns.

A Biogen spokeswoman said the Cambridge, Mass., biotech company is neither commenting on nor confirming the existence of additional cases as long as the PML rate is consistent with the rate of one-in-1,000 patients implied by the label. The new cases appear to be in line with the label’s rate.

An editorial published in the New England Journal of Medicine last week revealed a new case that occurred in Europe.

The latest case, also in Europe, was confirmed by Ralf Gold of the Ruhr University Bochum in Germany, who presented the case at the European Committee for Treatment and Research in Multiple Sclerosis that ended Saturday.

Like any public company, Biogen is required to disclose developments deemed material to its business, but the biotech company has said Tysabri’s risk profile is accurately detailed in its label after providing weekly updates on new PML cases through July 24, the third anniversary of Tysabri`s relaunch.

Duration of therapy is believed to play a role in Tysabri’s PML risk as most cases occurred after patients took the drug for more than a year. Biogen has opposed patients taking treatment breaks–referred to as “drug holidays”–because it can cause MS symptoms to return.

As of June 30, about 43,300 patients were taking Tysabri, with more than 30,000 on it for more than a year, and about 10,000 on it for more than two years.

Tysabri receives strong support from patients and doctors because of the drug`s perceived effectiveness. That support has remained steady because patients are well aware of the PML risk before they start taking Tysabri for the otherwise debilitating disease of MS.

Wall Street has closely watched the number of cases in gauging Tysabri’s sales trajectory because it is the key growth driver for both companies.

Sanford Bernstein analyst Geoffrey Porges said the two new cases “[add] to the dissatisfaction about the company’s decision to suspend regular disclosure of the rate of cases, particularly as a large bolus of patients are now reaching what appears to be a point of increased event risk.”

Mr. Porges said the new cases were “not necessarily alarming” because the ratio remains below the label-implied rate, but he stressed that there seems to be a connection to PML risk and duration of therapy.

PML re-emerged in Tysabri patients in July 2008, two years after the relaunch, and Biogen began issuing weekly updates in January after receiving criticism for its previous policy of disclosing new cases through 8-K filings with the Securities and Exchange Commission.

View full post here: http://online.wsj.com/article/SB125294848127909243.html

This is what happened when three people who were on Tysabri and other medications for Multiple Sclerosis had previously contracted the brain infection and two died, according to InjuryBoard.com which tracks such drug reactions. Then, the drug was taken off the market briefly.

Biogen Idec, the company that makes Tysabri (and other medications that help MS). This is the 11th case of the potentially fatal brain illness since July 2006 when the drug came back on the market for public use.

The PML, or progressive multifocal leukoencephalopathy, was responsible for the death of two patients and it was withdrawn in 2005, but then brought back with stricter monitoring efforts a year later.

According to InjuryBoard.com:

Four cases have been reported since the drug was introduced in 2006. Three have died. A patient had received 14 Tysabri infusions before falling ill.

The severe brain infection may occur in one in every 1,000 patients, according to Biogen statistics

Unlike the other MS medications, Tysabri is not an injection, but a montly infusion that takes a few hours to administer. It has been known to drastically change symptoms in some MS patients.

At the moment, 43,300 people are on Tysabri. The company expected to have more than 100,000 patients by the end of 2010.

Commentary: I’m on Tysabri and have been for nearly two years after being weaned off of Avonex. Make sure that you have regular checks by yout doctor, and let your family and friends know of potential PML symptoms.

View full article here: http://www.examiner.com/x-11509-Multiple-Sclerosis-Examiner~y2009m7d25-An-11th-patient-gets-potentially-fatal-brain-infection-using-Tysabri

Biogen Idec Inc.’s disclosure of a debilitating brain infection in a patient taking its Tysabri multiple-sclerosis medicine sparked a selloff in shares of the biotechnology company Monday.

The disclosure, made Friday evening, marks the 13th case of the infection, called progressive multifocal leukoencephalopathy or PML, in a Tysabri patient. Three of the patients have died.

Biogen’s shares dropped 5.5% to close at $47.32 on the Nasdaq Stock Market, possibly making the firm more vulnerable to a takeover by a large pharmaceutical company. Earlier this month, the company lost a proxy fight with billionaire activist investor Carl Icahn, who won two seats on its board and has suggested Biogen ought to be split up or sold.

Deutsche Bank downgraded Biogen’s shares to “hold” from “buy” over the weekend. Analyst Mark Schoenebaum estimated that of patients who have taken Tysabri for more than one year, one in 2,000 had contracted the infection. The company had previously placed that risk at one in 4,200, before the most recent cases.

American Depositary receipts in Ireland’s Elan Corp., which shares Tysabri’s profits, fell 6% to $6.94 in 4 p.m. trading on the New York Stock Exchange.

The risk of infections from potent drugs that restrict the immune system has recently vexed regulators. In April, the Genentech unit of Roche Holding AG pulled a psoriasis drug, Raptiva, from the market over PML. The cancer treatment Rituxan — sold by Roche and Biogen — has also come under scrutiny over cases of PML.

Tysabri was pulled from the U.S. market in 2005 after three initial cases. After holding hearings to weigh Tysabri’s risks and benefits, the Food and Drug Administration allowed it to be reintroduced in 2006, under monitoring rules and a prohibition on using it in combination with other MS drugs. The system was aimed at reducing PML incidence.

The 10 cases since — including three this month — have frustrated Biogen’s aim of making Tysabri into a blockbuster drug. The company has invested in treatments for PML and ways to mitigate the infection — once thought to be almost always fatal — and in persuading doctors that PML’s risk in Tysabri patients is less severe and less likely.

The drug missed Biogen’s projection for quarterly sales of $250 million last year — sales of the drug were $227 million from January to March — and Biogen has stepped back from a goal of reaching 100,000 patients by the end of next year.

“There are a number of neurologists who have started taking people off Tysabri for periods of time after they’ve been on it for a couple of years,” said John Richert, a neurologist who directs the research efforts of the National Multiple Sclerosis Society. Biogen opposes that practice, called a “drug holiday,” as unjustified.

But “when the odds that the person with MS is going to have significant disability, the 1 in 1,000 risk of PML, which was estimated early on, seems like a reasonable risk for many people,” Dr. Richert said.

Shannon Altimari, a Biogen spokeswoman, said the PML risk was “well within” what the company has said on Tysabri’s label.

Write to Keith J. Winstein at keith.winstein@wsj.com

View entire article here: http://online.wsj.com/article/SB124631389418370485.html

The company said late Friday it confirmed the presence of progressive multifocal leukoencephalopathy, or PML, on Tuesday. Biogen said the patient, who lives outside the U.S., had been using Tysabri for 30 months. Three of the ten cases of PML have been confirmed this month.

In morning trading, shares of Cambridge, Mass.-based Biogen slid $2.86, or 5.7 percent, to $47.21.

Tysabri is approved as a treatment for multiple sclerosis and Crohn’s disease. It was pulled from the market in 2005 due to concerns about PML, and sales resumed in July 2006 with restrictions and a monitoring program. The ten confirmed PML cases have all been in multiple sclerosis patients, and concerns about the disease have pressured sales of the drug.

Biogen said there were about 40,000 patients on Tysabri at the end of March, with 20,800 of them in the U.S.

Deutsche Bank analyst Mark Schoenebaum said in a note that the rate of PML infections in Tysabri patients is less than one in a thousand, for patients who have been on the drug for two years. He said the average time on Tysabri for the PML cases is 24 months, and that as more new infections appear, doctors may start taking patients off Tysabri sooner, or giving patients breaks from the drug.

Schoenebaum said that could “dramatically” reduce sales growth.

Biogen markets Tysabri with Irish drug maker Elan Corp. PLC, whose shares dipped 38 cents, or 5.2 percent, to $6.98. Shares of PDL BioPharma Inc., which developed the drug and receives royalties on sales from Elan, declined 6 cents to $7.90.

View full article here: http://www.businessweek.com/ap/financialnews/D994CK4G0.htm

Biogen Idec Inc., the maker of Tysabri, reported the case on Friday, one week after the 8th case was reported. The company indicates that they will no longer report each individual cases of Tysabri PML infections, but will provide a weekly update on their website.

Progressive multifocal leukoencephalopathy, commonly referred to as PML, is a rare form of brain infection that causes damage and inflammation to the white matter areas of the brain. The infection often results in death after the degradation of certain brain functions. Affects of the infection can include impaired speech, weakness, loss of vision, paralysis and cognitive decline.

Tysabri (natalizumab) was approved in 2004 for the treatment of multiple sclerosis through regular intravenous injections. It was recalled from the market in 2005 after three patients developed the rare brain infection, two of whom died. The medication was reintroduced in July 2006 with stronger warnings about the potential Tysabri side effects, and the drug was only made available under strict usage guidelines to limit the risk of PML infections.

Since its return to the market, this most recent report is at least the ninth patient to develop the infection. Estimates indicate that about one in every 1,000 patients treated with the Tysabri experience the side effect. The lastest case involves a patient outside the United States who developed the brain infection after his 34th injection.

Tysabri is just one of several drugs that have been linked to the deadly PML brain infections in recent years. The psoriasis drug Raptiva was recalled in April due to PML infections, and the cancer drug Rituxan was recently connected to 57 cases of PML infection in a study published in the May 2009 issue of the medical journal Blood.

June 12 (Bloomberg) — Biogen Idec said a patient taking its multiple sclerosis drug Tysabri was diagnosed with a life-threatening brain illness, the eighth case reported in the last year.

The patient was confirmed to have progressive multifocal leukoencephalopathy, or PML, on June 10, according to a report on Cambridge, Massachusetts-based Biogen’s Web site. About 56,700 patients have been treated with Tysabri, the company said.

Biogen and marketing partner Elan Corp pulled Tysabri from the market in 2005 after three patients developed the brain infection, including two who died. The U.S. Food and Drug Administration allowed sales to resume in July 2006 after deciding benefits for slowing MS relapses outweighed the risk. There were no reported infections for about two years after the drug’s reintroduction.

The likelihood of getting PML from Tysabri is about 1 in 1,000, according to the drug’s label. The infection occurs when a common germ, called JC virus, mutates, then evades the body’s immune defenses and penetrates the brain, causing irreversible damage. Researchers theorize that Tysabri may subdue defenses meant to keep the virus out of the brain. The virus breeds in brain cells, destroying them when it replicates.

On April 9, Genentech Inc., which was acquired in March by Roche Holding AG, announced it was pulling its psoriasis treatment Raptiva from the U.S. market because of the drug’s link to PML. Three patients were diagnosed since October and two died. Other drugs linked to PML include Roche’s Cellcept, used to prevent transplant rejections; Biogen and Roche’s cancer drug Rituxan; and Genzyme’s leukemia drug Campath.

Read full post here: http://www.bloomberg.com/apps/news?pid=20601087&sid=a3cQUIGdgeHM

The patient had been taking Tysabri for 31 months before developing the brain infection, the drugmaker said in a weekly update posted to its website on Friday, and spokeswoman Shannon Altimari added that more details of the PML cases will be presented at upcoming medical meetings.

Commenting on the announcement, Robert W. Baird analyst Christopher Raymond said that “while we applaud management’s decision to update PML cases weekly, we think it’s fair to ponder why this wasn’t fully discussed on the [first-quarter] earnings call,” which took place on Thursday April 16. Altimari responded that Biogen Idec has been “very clear” that updates for Tysabri would be posted on the company’s website on Fridays, and that the process set by the drugmaker had been followed.

Meanwhile, analyst Eun Yan of Jefferies & Company remarked that “while Biogen continues its clinical/commercial initiatives to drive Tysabri utilisation, sales uptick from physicians’ improved confidence on Tysabri…has yet to be seen.”

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LOS ANGELES, April 8 (Reuters) – Genentech Inc, which was acquired by Roche Holding AG last month, announced on Wednesday a phased voluntary withdrawal of psoriasis drug Raptiva from the U.S. market due to its link to a brain infection.

Raptiva has been associated with an increased risk of progressive multifocal leukoencephalopathy (PML), a rare and usually fatal disease of the central nervous system.

The drug, licensed from Xoma Ltd, had 2008 U.S. sales of $108 million.

Roche said it expects to record a $125 million charge for the withdrawal, but its 2009 targets would not be affected.

Authorities in Europe, where Raptiva is sold by Merck KGaA, recommended in February that the drug be suspended in light of the PML risk.

The European Commission is expected to follow that advice.

There have been three cases of diagnosed PML in patients receiving Raptiva and one patient treated with Raptiva who developed progressive neurologic symptoms and died of unknown causes.

Raptiva is approved for the treatment of chronic moderate-to-severe plaque psoriasis in adults 18 years or older who are candidates for systemic therapy or light therapy.

Genentech said that, effective immediately, physicians should not issue prescriptions for Raptiva for any new patients and should promptly contact patients currently receiving the drug to assess the most appropriate treatment alternatives.

The company said Raptiva will not be available after June 8 and estimated that around 2,000 U.S. patients may be receiving the drug for chronic plaque psoriasis. (Reporting by Deena Beasley; editing by Carol Bishopric and Matthew Lewis)

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BOSTON (Reuters) – Biogen Idec Inc said on Wednesday it is developing a test that can identify the presence of a virus that can cause a potentially deadly brain infection in certain patients taking its multiple sclerosis drug Tysabri, and hopes to have it available by year-end.

Cecil Pickett, Biogen’s head of research and development, said the company is working on an antibody-based test that can ascertain the presence in a patient’s blood of the JC virus, which can cause progressive multifocal leukoencephalopathy, or PML.

Tysabri, which Biogen co-markets with Ireland’s Elan Corp, is the biotech company’s most important product with 2008 sales of $813 million. But sales have been hurt by the drug’s association with PML.

It was withdrawn from the market in 2005 but reintroduced in July 2006 with stricter safety warnings as patients with the degenerative disease were willing to assume the risk given the drug’s clear benefits over other treatments.

Tysabri not only delays progression of MS but in some cases has shown improvement of disability.

Last month, Biogen scaled back growth projections for the drug, conceding it will not meet its previous forecast of 100,000 patients on Tysabri by the end of 2010.

But Dr. Al Sandrock, Biogen’s senior VP of neurology R&D, said the risk of developing PML appears to be less than originally believed.

Speaking at Biogen’s R&D Day for analysts and investors, Sandrock said since Tysabri’s reintroduction the PML rate is about 1 in 4,000 over 12 months of exposure. It was originally thought to be closer to 1 in 1,000.

Pickett said the company is placing a very high priority on developing the JC virus test, and hopes to have it available by the end of this year. But he said greater exposure to the virus does not necessarily predispose a patient to PML.

Other factors relating to a person’s immune system or mutations in the virus could also be involved, he said.

“It is a complicated research program and we need to sort these things out before we give guidance,” he said.

Five cases of PML have emerged in patients taking the drug since last July, and one has died.

Cambridge, Massachusetts-based Biogen emphasizes that patients who develop PML can now undergo a process called plasma exchange that removes Tysabri from their blood, meaning the disease is not necessarily fatal, which is helping give more confidence to physicians.

There have been suggestions that long-term Tysabri users stop taking the drug for a time — a so-called drug holiday — in order to reduce PML risk. Sandrock said Biogen is recommending against drug holidays as it likely decreases the drug’s benefit and may not improve safety.

“Within months you get a return of disease activity,” he said.

Roughly 60 percent of physicians believe Tysabri’s benefit outweigh its risk, Pickett said, down from 64 percent before the cases emerged in July. Still, data shows 74 percent of physicians expect to increase their use of the drug over the next six months.

Biogen’s shares closed up 67 cents, or 1.3 percent, at $51.52 on Nasdaq on Wednesday.

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SHARES IN drug company Elan bounced more than 10 per cent yesterday after news emerged of a possible treatment for a potentially fatal side effect of its multiple sclerosis therapy, Tysabri.

Biogen Idec, Elan’s partner in the development and sale of Tysabri, is testing the efficacy of a malaria pill developed during the Vietnam war in treating progressive multifocal leukoencephalopathy (PML), the brain infection that has been tied to use of Tysabri, according to Al Sandrock, Biogen’s head of neurology research.

Tysabri was pulled from the market in 2005 after three PML cases were reported. It was reintroduced a year later when US regulators said the medication’s effectiveness, twice that of other MS drugs, outweighed its risks.

However, the threat of PML has affected sales of the treatment which, although a successful drug in commercial terms, is well short of the figures initially expected.

In 2008, Tysabri generated $813 million (€604 million) in revenue.

The companies also reported five new PML cases since July, reigniting concerns of patients who believe a safer Tysabri would be their best treatment option, said John Richert of the US National Multiple Sclerosis Society. Without the risk, sales may more than triple, according to New York-based analyst Eric Schmidt.

Biogen may discuss its Tysabri safety efforts at a meeting today with investors and analysts to present its latest drug research.

Elan’s shares increased by 11.4 per cent to €4.48 in Dublin yesterday following news of the development.

Tysabri, a laboratory-engineered antibody, is designed to suppress the immune attack that leads to MS.

PML occurs when a common germ, called JC virus, mutates, evades the body’s immune defences and penetrates the brain, causing irreversible damage.

Biogen has been seeking a PML treatment since 2005, screening about 2,000 compounds known to fight brain infections.

The drug showing the most promise in laboratory tests was the commonly used malaria pill mefloquine.

A clinical trial is now testing mefloquine in 40 patients with PML from any cause, whether drug-related or from HIV.

The goal is to see whether mefloquine, sold by Roche Holding under the name Lariam, can treat PML when it occurs. The trial is expected to be completed by the end of the year. – (Bloomberg)

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