Panel judges Tysabri to be worth risk

Return of the multiple sclerosis drug to market is a major boost for Elan after a year of uncertainty following the deaths of two trial patients, writes Dominic Coyle

"We understand the risks of using experimental drugs but we also understand the risks of doing nothing."

The words of a young Utah mother to a distinguished panel of experts weighing up the fate of a breakthrough treatment for multiple sclerosis were representative of many patients who addressed the two-day hearing this week.

At stake was the future of Tysabri, a new drug, produced by Irish biotech company Elan and its US partner Biogen Idec, that has proven significantly more effective in reducing the symptoms of MS than previous drugs.

However, three of the 3,000 patients who took part in clinical trials of Tysabri developed a rare and generally fatal brain disease and the best medical minds are still unable to guess how many more might be at risk of the same disease in the future.

Pamela Clark of Salt Lake City told the 12-strong advisory committee - convened by the US Food and Drug Administration (FDA) to recommend whether to allow the drug back to market or effectively kill it off - that Tysabri had allowed her to walk to a duck pond with her two five-year-old sons. It had also let her stand up long enough to cook dinner.

She was one of dozens of MS patients, some in tears, who urged the panel on Tuesday to let them decide for themselves whether Tysabri's risks were acceptable. They said Tysabri produced dramatic improvements in motor function and should be available as long as patients know the dangers.

On the other hand, the husband and daughter of Anita Smith, who died while taking the drug, told the panel the 46-year-old woman should never have been offered Tysabri because her form of MS was mild.

She could walk up and down stairs and carry loads of laundry. A doctor who has since reviewed the case for the family agreed with their assessment and the family is suing both Elan and Biogen.

"We were never told Tysabri could result in Anita's death. If we had known that, we would have happily stayed away from the trial," said Beth Ann Smith, reading a statement for her father, Walter.

Patient testimony was pivotal in the decision of the committee to unanimously recommend the return of the drug to the market.

"It is likely there will be cases of PML, and likely we are going to see deaths," said the advisory panel's chairman, Dr Karl Kieburtz. "The point is, is there a reasonable balance that physicians and patients can reach together? The answer is yes, with some restrictions."

The decision has still to be approved by the FDA but it generally follows the recommendations of advisory panels and Dr Robert Temple, head of the FDA's Office of Medical Policy, indicated it would do so in this case.

Apart from patients, the decision is a major boost for both Elan and Biogen and marks another step on a 15-year path to develop a more effective treatment for the debilitating disease.

Tysabri was the first new drug in 10 years for MS, a disease in which the immune system turns on the body, attacking the protective coating of nerves in the brain and the spinal cord. It can cause blurred vision, numbness, fatigue and paralysis. Though not considered fatal, it can lead to complete disability.

Tysabri has been shown to be twice as effective as available drugs in preventing recurring bouts of MS, which affects an estimated 300,000 Americans, most of whom are diagnosed between the ages of 20 and 50.

Its effectiveness saw it fast-tracked through the regulatory process and put on sale in November 2004 before the FDA had even seen full two-year data for the drug's clinical trials - almost unheard of in the generally cautious drug approval process. It rapidly attracted 7,000 patients.

Less than four months later, it was suspended after the first two cases of progressive multifocal encephalopathy were diagnosed. A third case subsequently emerged in an intensive safety evaluation of all trials patients.

More PML cases likely will be seen if the drug returns to the market, the director of the FDA's division of neurology products, Dr Russell Katz, told advisory panel this week. The FDA does not know of any way currently to tell who is at risk for PML, and it is unclear if catching it early helps, he said.

"We fully expect additional cases of PML, many likely to be fatal," Dr Katz said.

Those cautions were taken on board by the panel which has recommended a number of significant restrictions on the drug, most notably that it should not be given in association with other MS drugs or immune modulators, not even in clinical trials.

It also suggested a strict monitoring programme of all patients on the drug. However, it stopped short of suggesting the drug should be used only for those patients who fail to respond positively to other treatments.

Assuming the decision is approved by the FDA, which is due to rule on the issue by the end of the month, Tysabri will be only the second prescription drug ever allowed back on the US market after being withdrawn on safety grounds.

When it first came to market, analysts predicted that it could become a "blockbuster" drug with peak sales in excess of $1 billion a year. This week some analysts were suggesting it could still achieve sales of around $700 million (€ million).

The FDA's Dr Temple said the patient testimony was "heart-wrenching" and helped clarify how much risk patients would accept. "I thought it was extremely, extremely useful," he told reporters.

Barbara Crooks told the committee that "life is all about trade-offs", and that she was willing to take a calculated risk in order to enjoy the benefit of Tysabri again. Ultimately the committee ruled that she should have that choice. - (Additional reporting, Reuters/LA Times service)