Biogen Idec Inc. (Nasdaq: BIIB) has identified high-risk patients taking its multiple sclerosis drug Tysabri who have a 1 in 100 chance of developing a potentially deadly brain infection from the medicine.
By analyzing the length of Tysabri use, previous treatments and results of a blood test for antibodies to the virus that causes the infection, doctors may spot patients with less than a 1 in 10,000 risk of progressive multifocal leukoencephalopathy, or PML, the analysis found. The drug’s U.S. label says the PML risk is 1.5 in 1,000 after two years of treatment.
Biogen manufactures the drug at its facility in Research Triangle Park, N.C.
The findings may change the way doctors treat multiple sclerosis, a progressive disease affecting 2.5 million people worldwide that robs patients of muscle control and balance. It may also boost sales of Tysabri, now limited to high-risk cases because of PML fears, to $3 billion annually from $1.2 billion in 2010 for Biogen and its partner, Dublin-based Elan Corp., said Corey Davis, an analyst at Jefferies & Co. in New York.
“For individuals who are negative, what we clearly know at least right now is that this is the most effective therapy we have available,” said Revere Kinkel, director of the Multiple Sclerosis Center at Beth Israel Deaconess Medical Center and associate professor at Harvard Medical School. “The pendulum is swinging to earlier and earlier use.”
Available in May
The test will be made available in Europe in May and shortly thereafter in the U.S., said Meena Subramanyam, senior director of clinical science and technology at Biogen. Kinkel has access to the test for research purposes and gives it to “virtually everybody” before starting treatment, he said.
About 57,000 patients worldwide take Tysabri, according to a Jan. 11 presentation by Biogen at the J.P. Morgan Healthcare Conference. Company research shows 50 percent to 60 percent of Tysabri patients test positive for antibodies to the JC virus that causes the brain infection.
The damage from PML, once thought to be immediately fatal, is substantial, according to another report released at the American Academy of Neurology meeting in Honolulu yesterday. Twenty-one Tysabri patients have died from PML through March 4.
Sixty-three of the first 79 Tysabri patients with the disease survived almost 10 months after diagnosis, said Patrick Vermersch, head of neurology at the University of Lille in France. Of those, 87 percent had moderate to severe disabilities, which make it difficult to keep a job or take care of oneself without help, said Kinkel, who moderated the session where the results were presented.
“It’s like the worst kind of imagined relapse,” he said. “It’s surviving, but they have significant disabilities.”
Biogen increased 77 cents to $82.96 at 4 p.m. New York time in Nasdaq Stock Market trading. The company’s shares have gained 52 percent in the past 12 months.
An analysis of 102 Tysabri patients who developed the brain disease found the greatest risk is in those who previously used powerful immune suppressing drugs like methotrexate, took Tysabri for more than two years and tested positive for the JC virus. A closer look at 25 patients found those who developed PML were positive for the virus before they started the medicine, said Alfred Sandrock, senior vice president of development for Weston, Massachusetts-based Biogen.
Knowing the odds may reassure patients taking the medicine and help doctors in their treatment decisions.
‘Not Entirely Proven’
“We have to tell patients at this point it’s not an entirely proven test, but it certainly will affect our decision making,” said Jack Ratchford, assistant professor of neurology at Johns Hopkins University in Baltimore. “What is done when someone tests positive depends on the individual. Often it is enough of a concern that the possible risk outweighs the benefit” and they stop Tysabri treatment, he said.
Some patients, particularly those with hard-to-control disease, elect to stay on the drug, Ratchford said in a telephone interview. The risk of disability from MS is higher than the risk of the infection for those patients, he said.
Studies have shown that after two years of Tysabri, 37 percent of patients taking the drug were free from active disease, including relapses and worsening disability, compared with 7 percent of those given a placebo.
Multiple sclerosis is neurological disorder thought to develop when a person’s immune system goes awry and attacks healthy cells in the central nervous system, according to the National Multiple Sclerosis Society. More than 400,000 Americans have the condition.
The risk of PML emerged after Tysabri was on the market, leading Biogen and Elan to suspend sales in February 2005. The drug returned to the market in June 2006 with a risk management program for patients who didn’t benefit from rival medications after research showed it was twice as effective as other drugs.
Doctors may think twice before starting patients who are positive for the virus on Tysabri, Ratchford said. Even testing negative isn’t completely reassuring because patients can be subsequently exposed to the virus, he said. In about 2.5 percent of cases, patients test negative when they have actually been infected, according to Biogen tests.
The risk of PML increases after the first year of treatment with the drug, and many doctors consider switching their patients after two years. A question remains about what medicine to use following Tysabri. Stopping treatment appears to trigger flares of the disease and may be detrimental, ruling out the idea of taking a patient off the medication temporarily to reduce the risk, studies at the meeting showed.
One new choice is Novartis AG (NOVN)’s Gilenya, the first pill to treat multiple sclerosis. It reduced the risk of worsening disability by 30 percent in patients who were previously treated with other drugs, said Gordon Francis, head of Novartis’s neuroimmunology clinical science unit.
The company, based in Basel, Switzerland, is considering a study of patients who want to start Gilenya after coming off Tysabri, Francis said. The goal would be to determine short-term risks and see how long patients must be off Tysabri, which can remain in the body for two months or more, before starting another treatment, he said.
Sales of Gilenya will increase as doctors become more comfortable with it, Francis said. Patients need to be monitored for a slow heart rate for six hours after their first dose, and then checked for vision changes a few months later.
Ultimately, the long-term safety of the drug will be what matters to doctors, he said. Older injected drugs like Avonex, Bayer AG (BAYN)’s Betaseron, German drugmaker Merck KGaA (MRK)’s Rebif and Teva Pharmaceutical Industries Ltd. (TEVA)’s Copaxone have been around for as long as two decades and doctors know what to expect with them, he said. They will remain “until the dust settles,” in perhaps three to five years, he said in an interview.
“There hasn’t been the stampede of the first Tysabri launch, and that is appropriate,” Francis said. “Neurologists are a conservative group, and they are even more conservative than they were five years ago because of Tysabri,” he said.
To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at email@example.com
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