Biotech Values

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Different non invasive test for JC virus:

Reviving Tysabri

http://www.forbes.com/2009/10/27/ms-crohn-elan-business-healthcare-tysabri.html?feed=rss_business_healthcare

Matthew Herper, 10.27.09, 3:59 PM ET

Worries about a potentially deadly side effect have long impeded sales of the multiple sclerosis drug Tysabri, made by Elan. But now the medicine's inventor says he has created a diagnostic test that might reveal those patients who are less at risk of the side effect. That could increase the market for the drug, which is already a $1 billion seller.

Ted Yednock, a researcher at the South San Francisco labs of Elan, invented the antibody that would become Tysabri in 1992. It offered a new way of curtailing the immune system, which goes haywire in MS and the gastrointestinal ailment Crohn's disease. The drug was approved to treat MS in November 2004.

But only three months after that approval, Tysabri was withdrawn. The immune suppression caused by the drug was allowing a usually dormant virus to infect patients' brains, causing a brain-destroying condition called progressive multifocal leukoencephalopathy (PML). Estimating that the virus occurred in one in 1,000 treated patients, the Food and Drug Administration allowed Tysabri to re-enter the U.S. market in July 2006.

Ever since, Yednock, 52, has been on a quest to understand the virus that causes PML. When Tysabri was pulled, researchers thought that most--90% or more--of human beings were infected with the virus that leads to PML (named JC, after the first two patients to get PML). Yednock says that work done by his team shows that only 50% of patients are infected with the JC virus, meaning that there are many patients for whom Tysabri might bear little PML risk at all.

Even with the specter of PML, 60,900 patients have chosen to take Tysabri, which is given by infusion and is very effective at preventing the brain lesions caused by MS.

Yednock's quest is taking on more urgency, as worries about PML continue to build. The risk of PML rises as patients get more infusions of Tysabri, and as time passes more PML cases are a certainty. On its most recent conference call, executives at Biogen Idec, Elan's partner on the drug, said that the FDA might want to add discussion of this increase to the product's label.

On Oct. 23, European regulators said that 23 cases of PML had been reported, far more than investors had expected. Wall Street analysts who cover Biogen for Bernstein, Deutsche Bank and Oppenheimer all said this could mean the risk of PML had doubled. The FDA-approved labeling for Tysabri puts the risk of PML at 1 in 1,000. With the new cases included, it could be 1 in 400, according to the analyst reports. Most analysts are skeptical that Elan and Biogen-Idec can reach their stated goal of getting 100,000 people on the drug.

Yednock says that the problem with PML testing up until now has been that the JC virus looks a lot like an evolutionary cousin, the BK virus. Antibody tests developed for JC virus were also set off by the BK virus, but BK virus doesn't cause the PML brain infection.

For some patients with JC virus, the virus is excreted in urine. By collecting blood samples from those people, Yednock had a group of patients he knew were infected with JC, allowing him to start developing a test that captured them all.

The test Yednock and his colleagues developed found that something like 50% of the patients have JC virus. There are eight cases of patients who developed PML where Elan and Biogen-Idec have blood samples going back long before the infection happened. All of those cases had JC virus antibodies in their bloodstreams a year before they got PML. "That's a pretty good starting point," says Yednock.

Elan has transferred the assay to a commercial laboratory, a step toward making it available to patients. The test, which uses antibodies to detect the presence of JC virus, could be done with just a saliva sample. It has not been evaluated by regulators or the larger scientific community, but the hope is that doctors might be able to use it to pick which patients are the best candidates for Tysabri therapy.

At a medical meeting Tuesday in San Diego, researchers working with Elan were set to present new analyses of already public clinical trials of Tysabri in Crohn's disease, a condition in which the immune system attacks the intestine, causing bleeding and sometimes requiring surgery. The new analyses show that Tysabri may work best in Crohn's patients who have already failed Crohn's drugs like Remicade, from Johnson & Johnson, and Humira, from Abbott Laboratories.

That's a nice step forward, but the PML risk needs to be clearly established. It would help Tysabri's makers a lot if they could identify patients who aren't at risk at all.