Monday, December 11, 2006

MS drug unlikely to gain OK for Crohn's

Biogen CEO: More development needed

By Jeffrey Krasner, Globe Staff | December 11, 2006

Biogen Idec's chief executive, James Mullen, says the Cambridge biotechnology company is unlikely to receive approval from European regulators to use its drug Tysabri to treat patients with Crohn's disease, a debilitating intestinal ailment.

Mullen said in a recent interview that results from drug trials included in an application to the European Medicines Agency are "interesting but need more development." Regulators are likely to require an additional clinical trial before approval, he said. That could take years and cost Biogen Idec millions of dollars.

"Almost irrespective of a regulatory response, it's going to need more clinical trials," Mullen said.

Biogen Idec and Elan Corp. of Ireland have partnered on development of Tysabri since 2001. After showing promising results in testing, the drug was introduced in the United States in November 2004 to treat patients with multiple sclerosis, but was abruptly withdrawn from the market after the companies found two patients in Tysabri trials had contracted a potentially fatal brain disease. Ultimately, three patients were found to have contracted the brain disease, progressive multifocal leukoencephalopathy, or PML, and two died from it.

After impassioned testimony from multiple sclerosis patients anxious for a chance to take Tysabri, the Food and Drug Administration last summer permitted sales to resume, but Biogen Idec was required to take additional safety precautions, including a mandatory registry of patients receiving the drug.

In recent public statements and discussions with stock analysts, officials from Biogen Idec and Elan said the firms planned to file an application to sell Tysabri to treat Crohn's with the FDA by Dec. 31. They also touted Tysabri's ability, demonstrated in clinical trials, to induce remission in Crohn's patients.

In their joint development of Tysabri, Biogen Idec has led trials and regulatory filings related to multiple sclerosis, and Elan has overseen its potential expansion as a treatment for Crohn's disease.

"The data suggest that Tysabri could be an alternative biologic choice for Crohn's disease patients," Elan said in a written response to questions regarding Mullen's comments. "As the data continue to unfold, [Elan and Biogen Idec] will explore additional indications, as appropriate, to unmet medical needs."

In a comprehensive safety review last year, the companies found two multiple sclerosis patients with PML who were also being treated with Biogen Idec's drug Avonex, another treatment for multiple sclerosis. One of those patients survived. Another patient in a Crohn's trial, who died from PML, had been treated with immunosuppressants.

That pattern suggested the risks of contracting PML while using Tysabri could increase if a patient is also being given a drug that affects the immune system. If so, that raises the risks of treating Crohn's patients with Tysabri, because many have weakened immune systems.

"Against the backdrop of PML, where you have a set of patients that already get bombarded with immunosuppressants over 20 to 30 years, [Crohn's] is not the first place we'd go to develop Tysabri," said Mullen. He said the drug looks more promising as a treatment for Lupus and certain cancers.

Biogen Idec and Elan share revenues from Tysabri, but failure to win approval to sell it as a treatment for Crohn's disease would not have much impact on Biogen Idec, stock analysts said.

"We stripped revenues from Crohn's out of our expectations when Tysabri was withdrawn from the market," said Jennifer Chao, biotechnology analyst with Deutsche Bank. "We have zero revenue expectations from Crohn's disease. My interpretation is that Jim Mullen is clearly trying to downplay any expectations for Tysabri around Crohn's disease."
But there could be an impact on Elan, a smaller company than Biogen Idec that is largely dependent on revenues from Tysabri.

William Tanner, an analyst with Leerink, Swann & Co., questioned the wisdom of trying to win approval to treat Crohn's patients with Tysabri. An unexpected side effect or death during Crohn's testing could endanger Tysabri's role in multiple sclerosis treatment , where it seems poised to become a blockbuster, he said.

"We predict $150 million in global Tysabri sales this year, growing to $474 million in 2007 and north of $1 billion in 2008," Tanner said. "There's not a lot of upside with revenues from Crohn's patients, so you have to wonder if the potential benefit is worth the risk."

Jeffrey Krasner can be reached at
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