Washington Editor

GAITHERSBURG, Md. - Members of an FDA advisory committee voted unanimously in favor of bringing Tysabri (natalizumab) back to the multiple sclerosis market, but with restrictions.

Calling the decision "a great day for patients," Burt Adelman, the executive vice president of development at Biogen Idec Inc., said the verdict also served as "an endorsement of our view and the regulatory agency’s view," on Tysabri’s efficacy and manageable risk profile. "Physicians and patients are going to have to sit down and make individual decisions."

Notably, the dozen voting members of the Peripheral and Central Nervous System Drugs Advisory Committee said no new trials are necessary, as close monitoring of any future treatment would essentially allow for further study to better define the immune system-modifying drug’s safety and efficacy profile. But at this point, Chairman Karl Kieburtz said that "there are sufficient data to move forward."

The FDA typically follows the advice of its advisory committees, and a final decision on Tysabri’s supplemental biologics application is due later thus month. Adelman said Cambridge, Mass.-based Biogen Idec could re-launch the products weeks later and noted that up to 100,000 patients in the U.S. could be eligible for treatment with Tysabri. He declined to forecast any sales projections and also demurred on the company’s pricing strategy.

The recommendations came during the second of a two-day public hearing on the MS drug, which was pulled off the shelves a year ago after three months of marketing because of its link to an often-fatal disorder called progressive multifocal leukoencephalopathy (PML), a risk currently estimated at 1-in-1,000.

Members of the committee acknowledged that PML would likely resurface, as did FDA officials, in future Tysabri therapy. "We assume we’re going to see them," said Robert Temple, the director of the FDA’s Center for Office of Drug Evaluation I, later adding that patients should assume dire consequences if PML is contracted.

Committee members all agreed that monotherapy would not eliminate Tysabri’s PML probability, although they didn’t endorse combination therapy with current front-line treatments as a good alternate option, either.

"I can’t believe anyone would want to recommend that at this point," said Justin McArthur, a neurologist from Johns Hopkins in Baltimore, although others said combination use could be explored down the road after the PML risk of monotherapy is better determined.

In trying to define patients appropriate for Tysabri therapy, which would be dosed monthly at certified infusion sites if it returns to the market, they agreed that a definitive MS diagnosis is imperative. They also favored its use in patients with relapsing features of the disease and said the drug should not be limited by the severity of a patient’s disability. Surprisingly, committee members were more torn on the issue of primary use, with seven saying it could be used as first-line therapy.

"We didn’t hear any recommendations for a very restricted approach to which patients should be treated," Adelman said, although the director of the FDA’s Division of Neurology Drug Products, Russell Katz, later said issues around first- and second-line therapy indications are "an unanswered question at the moment."

Committee members pointed to concerns around neutralizing antibodies and recommended regular screening as part of a mandatory risk-management plan that has been proposed by Biogen Idec. Such screening would exclude drug use in patients with high numbers of positive antibodies, which could lead to hypersensitivity reactions.

Committee members recommended that a proposed mandatory patient registry, which the company would update twice annually by contacting physicians, should include reports of deaths, PML, serious adverse events and other infections, as well as the use of intravenous steroids. Kieburtz, a neurology professor at the University of Rochester, said final registry details would "have to be negotiated" between the FDA and Biogen Idec. There was also committee opposition to assigning single vials to particular patients.

Several members suggested that a proposed observational study should have a control group. Biogen Idec has said it would evaluate the drug in 5,000 patients over five years to glean more adverse event information, absent a control, and would seek serious adverse event information in the study rather than through the registry. There was no firm consensus on the study, though, and again Kieburtz said the committee would leave final details up to the FDA and Biogen Idec.

Proposed checklists to watch for PML or other immunosuppressive symptoms received committee support, although FDA officials acknowledged that there would be difficulties in distinguishing between PML symptoms and exacerbations of MS. Also, Kieburtz noted that under-reporting or misreporting is "likely to occur," to some extent, given that patients have the burden of answering the questions. The checklists would be done monthly, in advance of each infusion, and failure to comply would preclude a patient from receiving Tysabri.

In support of the checklist’s self-reporting system, several committee members recommended regular MRIs at intervals as frequent as every six months, though no clear consensus was reached.

Should patients discontinue Tysabri treatment, committee members suggested that physicians use their own clinical judgment on the duration of a washout period before beginning another therapy. Alfred Sandrock, Biogen Idec’s vice president of neurology, recommended an eight- to 10-week period, and for the reverse, he advised a two-week washout period before putting patients on Tysabri.

Throughout the two-day meeting, numerous patients voiced their support for Tysabri, and after the final vote, John Richert of the MS Society said "we are very pleased" that the committee managed to "determine a reasonable balance" between the product’s efficacy and safety considerations. It remains under regulatory review in Europe, where an initial decision has yet to be reached.

The drug is partnered with Elan Corp. plc, of Dublin, Ireland. On Wednesday, shares in Biogen Idec (NASDAQ:BIIB) gained $3.50 to close at $49, and it continued to climb in after-market trading. Elan’s stock (NYSE:ELN) gained $3.11, or 24.5 percent, to close at $15.81.

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