Are narrow blood vessels to blame in MS?

By Genevra Pittman

NEW YORK | Thu Jul 14, 2011 12:13pm EDT

NEW YORK (Reuters Health) - Despite a few well-publicized studies and many hopeful patients waiting for treatment, there is no good evidence that multiple sclerosis, or MS, is caused by a blood vessel condition, a fresh look at the medical literature finds.

That means patients with MS shouldn't have surgery to open veins that connect the brain and spinal cord to the heart, researchers say.

"It's so appealing, the idea of a quick fix, of a surgical amelioration," Dr. Bridget Bagert, whose findings are published in the Archives of Neurology, told Reuters Health.

But, she added, "It's really not the right thing to do if the problem isn't established as being real."

MS occurs when the protective coating around nerve fibers begins to break down, slowing the brain's communication to the rest of the body. It's typically thought of as a disorder of the immune system and has no cure.

In 2009, however, Italian researchers led by Dr. Paolo Zamboni linked MS to a blood vessel condition called chronic cerebrospinal venous insufficiency, or CCSVI. The theory is that veins bringing blood from the brain and spine back to the heart become too narrow, causing some of that blood to leak back into the brain tissue.

Zamboni and his colleagues figured that might trigger inflammation, eventually leading to the balance and muscle problems seen in MS. Indeed, the Italian team's initial studies suggested that CCSVI is very common in MS patients and scarce in people without the disease.

But three independent studies published since then haven't found a clear link, according to the new report.

"That really casts a lot of doubt on to whether CCSVI exists at all, let alone whether or not it's the cause of MS," Bagert, from the Ochsner Clinic Foundation in New Orleans, told Reuters Health.

After Zamboni's initial findings were published, hopeful MS patients started requesting blood-vessel opening procedures, and a few doctors became well known in the MS community for being willing to perform them.

To determine if a person has CCSVI, a picture of the veins is taken using ultrasound or another type of scan. If the blood vessels look too narrow, doctors may open them up by inflating a small balloon in the veins.

Those procedures are typically used in people at risk of a heart attack, and they come with a risk of complications, including bleeding and infection.

But researchers said it's hard for doctors to even know what they're looking for on blood vessel scans, and whether anything that looks strange could be playing a part in MS symptoms.

"There's still considerable information and understanding that we don't have about this observation" on the role of CCSVI in MS, said Timothy Coetzee, chief research officer at the National Multiple Sclerosis Society in New York.

"There's no question that there has been considerable ambiguity and questions about some of the studies that were 100 percent (in favor of the link) and some that showed nothing," he told Reuters Health.

Bagert said there is also controversy over the methods used in the original Italian studies, which could have let potential investigator bias creep into the findings.

Because of the inconsistency in past reports, the National Multiple Sclerosis Society has spent more than $2 million funding research on how often blood vessel abnormalities show up in people with MS.

"Resolving this issue matters to a lot of people," said Coetzee, who was not involved in the new study.

He added that speculation about possible causes of MS -- which has included theories about infections and vitamin D -- is nothing new.

And as long as people with MS are well informed about the pros and cons of getting the procedure to open their blood vessels, he's not opposed to patients going ahead with the treatments for now.

But Dr. Ellen Marder of the University of Texas Southwestern Medical Center at Dallas, another author on the new paper, said the data doesn't support that idea.

"We don't think (CCSVI) is the cause of multiple sclerosis," she told Reuters Health. "We would not advise our patients to be tested for this or act on any recommendations based on this sort of testing."

SOURCE: bit.ly/nwrGWI Archives of Neurology, online July 11, 2011.

Panel backs stricter blood cancer drug label

By Anna Yukhananov

SILVER SPRING, Maryland | Thu Jul 14, 2011 6:12pm EDT

SILVER SPRING, Maryland (Reuters) - A U.S. advisory panel backed an experimental drug from Seattle Genetics Inc for treating two rare types of blood cancer, but recommended stricter labeling than the company sought.

The move could restrain Seattle Genetics' plans to expand use of the medicine, which is currently proposed for two types of blood cancer -- Hodgkin's lymphoma and anaplastic large cell lymphoma (ALCL) -- that affect just over 10,000 Americans a year.

The Food and Drug Administration advisory panel unanimously recommended on Thursday that the drug, Adcetris, get accelerated, or conditional, approval until the company conducts more studies to confirm safety.

Seattle Genetics shares, which were halted during the panel meeting, were down 6.6 percent to $18.99 on Nasdaq in after-hours trading.

"It's an excellent drug, but we need more experience with it overall," said panel member Dr. William Kelly, professor of medical oncology and urology at Thomas Jefferson University.

The company originally asked for full approval for Adcetris in patients who had already been treated for ALCL. About 2,000 new cases of ALCL were diagnosed in 2010, the company said.

The panel also recommended the drug for patients who have already tried a stem cell transplant to treat Hodgkin's lymphoma, another relatively rare blood cancer.

About 9,000 Americans are diagnosed with Hodgkin's lymphoma each year, but restricting it to patients who have already tried a stem cell transplant could also limit sales.

FDA staff reviewers suggested narrowing the approved patient group for Hodgkin's treatment in documents released on Tuesday, sending Seattle Genetics shares down 3.6 percent.

The FDA usually follows the recommendations of its advisory panels and is due to make a final decision on the drug by August 30. If approved, Adcetris will become the first FDA-backed drug for Hodgkin's since 1977.

Howard Liang, an analyst at Leerink Swann, sees U.S. sales at more than $400 million for both types of cancer in 2015.

But the CEO of Seattle Genetics, Clay Siegall, told Reuters in May sales could be well over $1 billion if the drug wins approval as a first treatment option for ALCL and Hodgkin's, not just for previously treated patients. The company is currently conducting studies for that, he said.

SMALL TRIAL SIZE

The FDA granted priority review status for the drug, known chemically as brentuximab vedotin, meaning the agency believes the medicine is a potentially significant advance over existing therapies.

Brentuximab vedotin links a tumor-targeting antibody to a cancer-killing chemotherapy drug with the goal of limiting side effects. It is designed to home in on an antigen, or foreign substance, in Hodgkin's lymphoma, several types of T-cell lymphoma and other hematologic malignancies.

But the agency said the company needs more studies confirming safety and efficacy before the drug can get full approval.

"No one is debating the level of activity of this drug," said panel chairman Dr. Wyndham Wilson, chief of the lymphoma therapeutics section at the National Cancer Institute.

"This to me seems the perfect example of a drug that should be approved under accelerated approval."

In mid-stage trials, three-quarters of patients had some tumor shrinkage after taking Adcetris for Hodgkin's and about a third had complete remission, or disappearance, of the disease. For ALCL, 86 percent had a response and over half had complete remission.

However, the mid-stage trials only included 58 patients for ALCL and 102 patients for Hodgkin's and did not compare Adcetris to another drug. The FDA said these factors made it difficult to pinpoint the drug's safety and called on the company to develop follow-up studies by August 30, or risk having approval revoked.

"If we do not come to an agreement on an appropriate program, with the company by August 30, you will be seeing us again at this committee," said Dr. Richard Pazdur, head of the FDA's Office of Oncology Drugs.

The company said it was confident of coming to an agreement with the agency before that date.

"We're looking forward to working with the FDA to define our development plan," CEO Siegall told reporters. "This is our highest priority of the company."

(Editing by Tim Dobbyn and Andre Grenon)