FDA takes a closer look at withdrawn MS drug
Tysabri is on center stage as FDA debates balance between speed and safety
By Aaron Smith, CNNMoney.com staff writer

NEW YORK (CNNMoney.com) - The FDA's balancing act between safety and speed is taking center stage with the multiple sclerosis drug Tysabri.

Two biotechs -- Biogen Idec from Cambridge, Mass. and Elan Corp. from Dublin -- are trying to get their multiple sclerosis drug Tysabri back onto the market. They're losing money on the drug's absence with every passing day, and some patients are clamoring for the drug's return. But two deaths have been attributed to it.

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"I think the drug probably returns to market, but it returns in handcuffs," said Bernstein analyst Geoff Porges. Prior to market withdrawal, Porges projected $3 billion in annual sales for Tysabri, but he's lowered that projection to $700 million. Biogen Idec totaled $2.4 billion in 2005 sales for all its products, and Elan totaled $490 million in sales that year.

Biogen Idec (up $1.18 to $48.50, Research) and Elan (down $0.09 to $14.17, Research) put Tysabri on the market in November of 2004, after the FDA approved it as a treatment for MS. The drug was effective in slowing the onslaught of this disabling disease, which attacks the central nervous system, and preventing relapses. Some analysts touted the drug as a potential blockbuster. After the biotechs put Tysabri on the market, they continued to test it for MS, as well as a potential treatment for Crohn's disease, which causes inflammation of the digestive tract, and for rheumatoid arthritis, which causes inflammation of the joints. That's where they ran into trouble.

On Feb. 28, 2005, Biogen Idec and Elan told the FDA they were taking Tysabri off the market and suspending their late-stage clinical trials. Three of the trial patients were diagnosed with progressive multifocal leukoencephalopathy, or PML, a nervous system disorder affecting people with weakened immune systems, including about 10 percent of all AIDS patients, according to the companies. Two of the patients with PML died, one of them during trials and one of them after the trials ended, said Davia Temin of Elan. She said the patients who died were also taking immunosuppresents. The companies said that 3,000 patients participated in clinical trials and another 5,000 patients have used Tysabri.

The drug is still off the market. But on Feb. 15, 2006, nearly a year after the withdrawal, the FDA allowed trials to resume, but only with people who were previously treated in a Tysabri study. FDA advisors will meet on March 7 and 8 to sift through safety and efficacy information and try and figure out what else to do with Tysabri. The advisory committees generally make recommendations to the FDA, but the FDA did not confirm whether the committee would be taking a vote at its upcoming meeting.

In an apparent vote of confidence, Standard & Poor's upgraded Biogen Idec on Wednesday, to BBB from BB-plus, with a stable outlook.

Bringing back Tysabri

Tysabri patients will be making an appearance at the committee meeting to lobby for the drug's market return, said Temin of Elan.

"There has been a huge patient outcry for the drug because it has been proven to be highly effective against what has proven to be a highly intractable disease," said Temin, referring to MS. "We are working very closely with the FDA from the beginning and clearly are putting the safety of patients first, but also want to respond to patient need and desire to getting the drug back on the market."

Jason Kantor, analyst for RBC Capital Markets, said the meeting "ought to have a pretty positive tone to it because it's going to be dominated by a lot of people's testimony about how the drug is beneficial to them and how having the drug off the market has made them worse."

The companies submitted their Tysabri application for the treatment of rheumatoid arthritis and Crohn's disease to the FDA on Sept. 26, 2005. The FDA gave the experimental drug candidate a priority review status. This means that the agency tries to review it within six months, instead of its usual goal of 10 months, because it has life-saving potential and addresses an unmet need. If the FDA meets its own goals for priority review, then a decision on Tysabri would be reached by late March.

The FDA is currently locked in a tug-of-war between safety and speed. The agency has requested, as part of its budget, an additional $6 million to fund Critical Path, the effort to speed up review without sacrificing safety.

The FDA wants to avoid scandals like Vioxx, Merck's arthritis painkiller that was approved by the FDA in 1999 but then pulled off the market in 2004 after a study showed an increase in the risks of heart attacks and strokes in patients who took the drug at least 18 months, prompting nearly 10,000 lawsuits against Merck. Other drugs from the arthritis painkiller class were affected. Pfizer pulled its arthritis painkiller Bextra off the market in 2005, but was allowed to continuing marketing Celebrex with a sterner warning label. All of these drugs were blockbusters, with combined annual sales totaling $8 billion before the troubles emerged.

But critics of the FDA say the agency should not take too long reviewing drugs with life-saving potential, because patients die while waiting for the new treatments to become available. The critics say the FDA will never be able to detect all the risks, because some of them don't become evident in patients for years.

The future of Tysabri

So what's going to happen to Tysabri?

"I think most people believe that this drug is going to come back to market with a restricted [warning] label," said Kantor, the RBC analyst. "But I think there is considerable risk that the FDA will give Tysabri an approvable letter and ask for more data in a clinical trial setting before making it widely available."

Clinical trials are expensive and time-consuming. Amy Brockelman, spokeswoman for Biogen Idec, said the company is setting itself up to resume Tysabri trials in the next few weeks. The next trial would focus on safety for MS patients, said Brockelman, and many of the patients from previous Tysabri trials have shown interest in participating.

Brockelman said the companies might eventually resume studies for Crohn's disease, but are not planning to resume trials for rheumatoid arthritis.

The read more about the FDA's balance between speed and caution, click hereTop of page

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