Review by US drug regulator will determine fate of Elan's Tysabri

Staff at the US drug regulator last night said the risks of Elan's multiple sclerosis drug Tysabri remain unclear. Company executives, however, are confident the drug will be approved to return to market.

As representatives of Elan, its US partner Biogen Idec, patients and opponents of the drug gathered in Maryland for a two-day review by outside experts that will determine the fate of the drug, staff at the Food and Drug Administration (FDA) said it was still not known whether Tysabri increased the chances of a life-threatening brain infection when used alone, or if the problem occurs only when it is combined with other drugs that may suppress the immune system.

The FDA's Office of Drug Safety said Elan and Biogen should be forced to impose strict patient monitoring requirements if Tysabri is allowed to return, the staff said.

Lars Eckman, president of global R&D at Elan, says the company is already committed to operating a registry of all Tysabri patients that will allow for close monitoring of the drug's safety.

"I think it is prudent for us to have a system in place where we can monitor data from all the patients and where we can capture any possible adverse event".

Tysabri was withdrawn just over a year ago after two patients in clinical trials were diagnosed as suffering from a rare and generally fatal brain infection, progressive multifocal leukoencephalopathy (PML). A subsequent case was uncovered in what Elan has described as the largest safety evaluation of its kind ever undertaken.

Speaking to The Irish Times, Dr Eckman also said it was accepted by all sides that amended labelling for the drug would rule out treatment with other immune modulators - such as those identified in the three cases of PML uncovered, including Biogen's Avonex. "We have said all along that Tysabri should not be combined with immune modulators. That moves it into the monotherapy territory."

He believes the drug is strongly positioned to return to market and is particularly pleased by the number of patients who will address the advisory committee. "We believe the efficacy of the drug and the unmet need will be so strong that the FDA will approve the drug. Ultimately the decision is in their hands but we have a very strong case.

"The patients will play a significant role in the FDA's overall assessment of the drug," said Dr Eckman. "They will have a significant voice at the meeting and the FDA has said that the patients' opinion is very important. They will be a very big presence - an unusually big presence at this hearing."

Dr Eckman, who oversaw the 12-month safety evaluation of all 3,000 clinical trial patients for Elan, acknowledges the initial findings of PML were a blow to the company. "It was a big disappointment in the beginning because we had been working on this product for 15 years."

He is confident that the safety evaluation, together with subsequently produced two-year clinical data that showed the drug was even more effective than originally thought, have allowed Elan and Biogen put together a new risk management plan that will be acceptable to the FDA.

"Primarily because of the risk of PML, which is not well-quantified, it is unclear for which patients the risk-benefit profile would be acceptable," the FDA staff wrote. Many MS patients have a "relatively benign disorder" and Tysabri may be too risky for them, the staff said.

Dr Eckamn notes that no other drug has emerged on the scene to compete with Tysabri on efficacy. We are very much in the position we were in last year, he says. "We have a drug that is highly efficacious and we have a huge unmet need among the patients. We are convinced this will create a business opportunity for Elan and Biogen and a treatment opportunity for the patient."

The FDA staff agreed Tysabri offers unique benefits. Clinical trials to date showed the drug offered "approximately twice the benefit of currently available first-line treatments for MS".

The advisory panel will give its decision at the end of the two-day hearing. The FDA usually follows the advice of its outside panels though it is not compelled to do so. However, the agency has already approved the reintroduction of Tysabri for patients on the clinical trials.

Patients in the wider community, the companies and their shareholders will not have long to wait as the FDA is required to announce a decision on Tysabri by March 29th.