This would be very nice.
bloomberg.com
Biogen Tests Malaria Drug as Cure for Tysabri Brain Infection
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By Elizabeth Lopatto
March 24 (Bloomberg) -- Biogen Idec Inc. may have found a treatment for the deadly brain infections that have been tied to use of its multiple sclerosis drug Tysabri, the biotechnology company’s fastest-growing product.
A malaria pill developed during the Vietnam War is being tested by Biogen on patients with progressive multifocal leukoencephalopathy, the brain disorder known as PML. Tysabri was pulled from the market in 2005 after three PML cases were reported. It was reintroduced a year later when U.S. regulators said the medication’s effectiveness, twice that of other MS drugs, outweighed its risks.
In 2008, Tysabri generated $813 million in revenue for Cambridge, Massachusetts-based Biogen and its marketing partner, Elan Corp., of Dublin. 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 National Multiple Sclerosis Society. Without the risk, sales may more than triple, said Eric Schmidt, a Cowen & Co. analyst in New York, in a telephone interview.
“If they resolved that dangerous situation, I would definitely resume therapy with Tysabri,” said Suzanne Carroll, 53, a Toledo, Ohio, radio-show host who stopped taking the medicine when she developed pneumonia and shingles. Her doctor told her those infections indicated she may be vulnerable to PML, Carroll said.
“I really felt great on the drug,” said Carroll, who produces radio program, “The Jazz Brunch.” “It disappoints me so strongly that I’m not able to take it.”
Investor Meeting
Biogen may discuss its Tysabri safety efforts at a meeting tomorrow with investors and analysts to present its latest drug research. The company yesterday rose $1.53, or 3.1 percent, to $51.50 in Nasdaq Stock Market composite trading, after dropping 13 percent in the 12 months before today. Elan’s shares rose 4.7 percent, or 18 cents, to 4.02 euros in Dublin.
MS, a neurological disease affecting 400,000 Americans, robs people of muscle coordination and balance, sometimes leading to damaged vision and paralysis. The malady is caused when the immune system mistakenly attacks myelin, a protective coating on nerve fibers, disrupting the brain’s communication with the body.
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, 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.
2,000 Compounds
Biogen has been looking for 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 Basel, Switzerland-based Roche Holding AG under the name Lariam, can treat PML when it occurs, preventing more brain death. The trial is expected to be completed at year’s end.
“It’s been used in thousands of patients for malaria and, if it can help, why wouldn’t you use it?” said Al Sandrock, Biogen’s head of neurology and research, in a telephone interview. “We knew we didn’t have time to develop a brand-new drug from scratch, but we thought there might be a drug that’s already been approved that might be effective against the virus.
‘Penetrated the Brain’
“We chose mefloquine because we knew it penetrated the brain very well,” he said.
In the trial, patients with PML are given 250 milligram pills of mefloquine for the first three days after they are diagnosed with PML. They then get the drug weekly for as long as six months.
Biogen’s plan is to develop a PML protocol in which patients are first treated with a blood-cleansing method known as plasma exchange, or PLEX, which takes blood from the body, separates the plasma, and returns the blood to the body. This process washes Tysabri out of patients’ blood, allowing the immune system to fight the infection. Mefloquine would be given next, before a patient resumes taking Tysabri.
The company has already demonstrated success with PLEX, and the procedure is becoming a standard of care in treating Tysabri PML cases. Its use was added to the drug’s prescribing information in October.
Plasma Exchange Findings
A Biogen-funded study from the Cleveland Clinic in February found that in 12 Tysabri users who didn’t have the brain disease, three sessions of the treatment lowered Tysabri levels to an amount that may stop the progress of PML. All five recent patients on Tysabri have been treated with plasma exchange, said Robert Fox, a neurologist at the Cleveland Clinic and the study’s lead author.
“The protocols I’ve seen” for managing PML from Tysabri “all include PLEX as the cornerstone of management,” Fox said.
The U.S. Food and Drug Administration approved Tysabri’s return in 2006 after patients pleaded for the drug at a public hearing. The likelihood of getting PML is about 1 in 1,000, according to the drug’s label.
Still, anxiety about PML led Chief Executive Officer James Mullen, in a Feb. 6 conference call, to abandon a forecast that 100,000 patients will take the drug by 2010. He said he couldn’t affirm that outlook, after reporting the fifth case of the illness since the drug’s reintroduction.
“If we had assurances from clinical data that we could control PML and prevent the severe consequences of the disease, we’d reduce a lot of the aversion to the drug,” said Richert, executive vice president of research for the MS Society in New York, in a telephone interview.
Severe Disease
Fox said some of his patients are reluctant to take Tysabri because of the PML risk. People with severe MS are more willing to try the drug than are those in earlier stages of the disease because of its effectiveness, he said.
“I’ve had patients who merited the drug, but they were nervous about it, and then they had a pretty severe relapse and changed their minds,” Fox said. “It’s a fear relative to the disease.”
If PLEX and the malaria drug work against PML, this treatment may also be helpful to patients on at least four other drugs that have been linked to the brain infection, according to Naomi Aoki, a Biogen spokeswoman. Those include Roche’s Cellcept, used to prevent transplant rejections; Biogen and Genentech Inc.’s cancer drug Rituxan; Genentech’s psoriasis drug Raptiva, and Genzyme Corp.’s leukemia treatment Campath.
To contact the reporter on this story: Elizabeth Lopatto in New York at elopatto@bloomberg.net.
Last Updated: March 24, 2009 00:00 EDT |
