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.

The drug, BG-12, also met the secondary goals of the study, according to Biogen, which sells the multiple sclerosis treatments Tysabri and Avonex.

In the study of more than 1,200 patients, BG-12 administered either twice or three times a day showed a highly statistically significant reduction in the number of patients who relapsed at two years compared with placebo.

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).

The first of an eventual 1,500 patients needed worldwide was enrolled last month in the U.S. The drug, daclizumab, is being developed for monthly injection under the patient’s skin by North Chicago-based Abbott and Cambridge-based Biogen Idec.

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.

View full post here: http://industry.bnet.com/pharma/10005010/biogen-idecs-tysabri-problems-may-be-fault-of-european-doctors/?tag=shell;content

Biogen Idec has succeeded in extending patent protection for its multiple sclerosis drug Avonex to 2026, some 13 years beyond the original patent-expiration date. The IP sleight of hand comes in the form of a newly issued method-of-use patent, which also covers Avonex treatment of multiple sclerosis. The recombinant beta interferon drug is big seller for the big biotech, says Reuters.

In ongoing development of Avonex, the drug maker is currently conducting trials of a long-acting version.

More good news on Avonex for Biogen Idec:  Data from a Phase IIII study show that MS patients using the drug report “significantly fewer” injection site reactions compared with patients on Betaferon, Copaxone or Rebif. Avonex-takers also were less likely to have missed a dose due to an injection site reaction in the four weeks prior to first assessment than those on other therapies.

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

Some people have had severe allergic reactions, a drop in their red or white blood cell levels, a drop in cells that help to form blood clots, heart problems, changes in their thyroid function, or seizures.

Your liver may be affected by taking AVONEX and a few patients have developed severe liver injury. Your healthcare provider may ask you to have regular blood tests to make sure that your liver is working properly. If your skin or the whites of your eyes become yellow, or if you are bruising easily, you should call your healthcare provider immediately.

AVONEX has not been studied in pregnant women. If you become pregnant while taking AVONEX, you should stop taking AVONEX immediately, tell your healthcare provider, and consider enrolling in the AVONEX Pregnancy Registry by calling 1.800.456.2255.

Most people who take AVONEX have flu-like symptoms (fever, chills, sweating, muscle aches, and tiredness) early during the course of therapy. For many people, these symptoms lessen or go away over time. Talk to your healthcare provider if these symptoms continue longer than the first few months of therapy, or if they are difficult to manage. In addition, you can refer to the Patient Medication Guide. This information is not intended to replace discussions with your healthcare provider.

Since AVONEX was approved in 1996, healthcare providers have developed successful ways to manage some of the more common AVONEX side effects, such as flu-like symptoms.

You should discuss ways to manage any AVONEX side effects you may have with your healthcare provider.

Few people quit due to AVONEX side effects

Very few people stop taking AVONEX because of side effects such as flu-like symptoms (fever, chills, sweating, muscle aches, and tiredness).

In a 2-year study, very few people (4%) stopped taking AVONEX due to side effects.

In a longer, 8-year follow-up study, even fewer people (2%) stopped taking AVONEX due to side effects.

Injection site reactions

AVONEX is the only MS therapy delivered by an injection into the muscle (IM). All other injectable MS therapies are delivered under the skin (subcutaneous). In clinical studies, only 3 out of 100 people taking AVONEX had reported injection-site reactions often seen with other MS therapies.

For more information, refer to the patient Medication Guide. This information is not intended to replace discussions with your healthcare provider.

View full prescribing info here: https://www.avonex.com/msavProject/avonex.portal/_baseurl/threeColLayout/SCSRepository/en_US/avonex/home/consider-avonex/ms-treatment-overview/AVONEX-side-effects.xml

Elan starts legal action in drug row with Biogen

By Andrew Jack

Published: August 6 2009 22:34 | Last updated: August 6 2009 22:34

Elan has launched legal action to prevent the “irreparable injury” that would be caused by the collapse of its partnership with Biogen Idec over its pivotal multiple sclerosis drug.

The Ireland-based pharmaceuticals company is challenging a claim from Biogen Idec, based in Boston, that Elan’s recent $1.5bn (£893m) deal with Johnson & Johnson placed it in “material breach” of their profit-sharing agreement for Tysabri.

In a filing with the US District Court, Elan said it had received a letter from Biogen Idec at the end of last month giving it notice that it was terminating the collaboration agreement first signed to develop and commercialise Tysabri in 2000.

That letter gives the two companies 60 days – until late September – to finalise a restructuring of their Tysabri partnership, only days after J&J’s equity investment and funding deal is set to be completed with Elan.

Biogen Idec argued that following Elan’s deal with J&J, announced last month, its partner was in “material breach” of the agreement, which is rendered void by any delegation of rights.

Shane Cooke, Elan’s chief financial officer, told investors in a conference call last month that J&J had agreed in a confidential aspect of its deal to help finance the purchase of Biogen Idec’s share in Tysabri in the event that there was any change of control.

However, in a view that Elan maintained in Thursday’s court filings, Mr Cooke also stressed that the J&J deal did not in itself represent any change in control that would affect the existing Tysabri partnership with Biogen Idec.

Elan has since offered to share the full terms of the J&J financing agreement with Biogen Idec, and has now filed them with the court in an attempt to win a ruling that there is no violation.

It says in the filing that termination of the partnership would result in Elan forfeiting all rights to Tysabri or the ability to buy out Biogen Idec’s rights to the drug, and imposing on it “draconian penalties”.

Elan said on Thursday: “There’s nothing in the pending transaction that is contrary to our collaboration agreement with Biogen Idec for Tysabri … This is the same agreement we have been operating under for the last nine years. It is unfortunate that, because of Biogen Idec’s actions, Elan was left with no alternative but to seek court intervention to protect its interest.”

View full post here:

http://www.ft.com/cms/s/0/f7fe7f32-82bd-11de-ab4a-00144feabdc0.html?ftcamp=rss&nclick_check=1

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

Is anyone else tired of hearing that drug companies care more about profits than patients? Me, too. But even more tiresome than the anti-pharma rhetoric is the fact that industry keeps pouring fuel on the fire.

True, most drug makers got into the business in order to help people. “Making medicine is hard, folks,” Michael Zimmer (zayzayem.wordpress.com) eloquently notes on his blog. “Honestly, if all they wanted to make was money, they would be making porn.”

But the bad behavior of industry keeps muddying that simple insight. I’m not even talking about the big pharma marketing scandals and fake medical journals – I’m talking biotech here.

A fair bit of it doesn’t even get picked up by the lay press (for which biotech should thank its lucky stars). Like last month’s spat between Biogen Idec and Genentech over the development of Rituxan (rituximab) and follow-on anti-CD20 antibodies. Biogen Idec didn’t want Genentech to advance the drugs for new indications like neuromyelitis optica, multiple sclerosis and lupus because the new approvals would lower Genentech’s royalty rate to Biogen Idec. Way to prioritize getting new drugs to patients in need.

The recent spate of headline-grabbing proxy fights hasn’t helped the industry’s cause either. As Karl Thiel wrote in a recent BioWorld Perspectives column:

In a fight between rich corporate raiders and the management of modestly sized biotech companies, all my instincts are to side with the latter.

I mean, on one hand you have the leaders of an industry trying to harness cutting edge science to bring new medicines to the sick. On the other, you have some of Wall Street’s most brazen and aggressive personalities looking to pad already immense fortunes. As popularity contests go, it seems like a pretty uneven match-up.

So it pains me a bit to say that in the growing number of battles between companies and activist investors, it’s the Wall Street guys who have been coming out looking more reasonable than our homegrown champions of medical progress.

He’s referring to companies like Avigen, which preferred to sit back and collect salaries rather than liquidate as shareholders requested or consider what appeared to be an attractive acquisition by MediciNova. And then there’s Enzon Pharmaceuticals, whose CEO can “almost never” be fired and makes an inordinately large salary, according to activist shareholders. Honestly, I felt a little guilty last month for criticizing Enzon’s $250,000 to $500,000 per year price for ADA-SCID drug Adagen (pegadamase bovine) after readers pointed out that as an ultra-orphan disease, Enzon has to charge that much to make a profit. But maybe they could charge less if they reconsidered their executive pay policies.

Another black eye for biotech came with last month’s ACLU lawsuit against Myriad Genetics over gene patenting. And I’m sure there are some I’m forgetting.

Every industry has a few bad apples… but it might behoove biotech to stay on its best behavior, for the sake of all that biotech-related legislation making its way through Congress.

Oh yeah, and maybe because it’s the right thing to do, too.

View entire post here: http://industry.bnet.com/pharma/10003018/tired-of-patients-vs-profits-quit-throwing-fuel-on-the-fire/

Biogen Idec (NASDAQ: BIIB) today announced the U.S. Food and Drug Administration (FDA) has granted PEGylated interferon beta-1a (BIIB017) Fast Track designation for relapsing multiple sclerosis (RMS). Biogen Idec is currently enrolling patients in a global Phase III study evaluating the efficacy and safety of either bi-weekly or once-monthly injections of PEGylated interferon beta-1a in this patient population.

“Early-stage clinical trials suggest that PEGylated interferon beta-1a has the potential to offer less frequent dosing without compromising efficacy, which would be a significant development for people living with multiple sclerosis,” said Michael Panzara, M.D., M.P.H., vice president and chief medical officer of neurology at Biogen Idec. “We look forward to working closely with the FDA to expedite the compound’s development and review process.”

The FDA’s Fast Track program is designed to expedite the review of new drugs that are intended to treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs.

Biogen Idec plans to enroll more than 1,200 patients in the Phase III, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of PEGylated interferon beta-1a in patients with RMS. The global trial, called ADVANCE, will determine the efficacy of PEGylated interferon beta-1a in reducing relapse rates in patients with RMS at one year. The study will also examine if, over time, treatment with PEGylated interferon beta-1a can slow disease progression and lead to a decrease in the number of T2 hyperintense brain lesions commonly seen in MS patients.

Patients interested in learning more about the ADVANCE trial may speak with their physician or e-mail ADVANCEstudy@biogenidec.com.

View entire post here: http://newsticker.welt.de/?module=smarthouse&id=912611