The FDA is allowing Tysabri to return to the market in a limited capacity for multiple sclerosis patients, three months after an advisory committee voted unanimously in favor of doing so.
The companies behind Tysabri (natalizumab), Biogen Idec Inc. and Elan Corp. plc, expect to make it available next month after the FDA signs off on all aspects of an accompanying risk-management plan, which is designed to ensure that patients are educated and provide continuing data.
"The benefits of this drug outweigh the risks for this particular condition," said Steven Galson, the director of the FDA's Center for Drug Evaluation and Research, during a conference call. He added that patients are ready to take the drug, despite its well-chronicled risks. "That's why we're doing it."
The product's reintroduction represents a 180-degree about-face for Tysabri, which last year was removed voluntarily from the market by Biogen Idec because of its link to a viral infection called progressive multifocal leukoencephalopathy (PML), which can lead to death.
Because of that risk, the FDA is recommending its use be restricted to patients who have had an inadequate response to, or are unable to tolerate, alternate MS therapies. The monoclonal antibody is indicated for use as a monotherapy "because we don't know enough" about possible interactions with other immunosuppressive drugs, Galson said.
Notably, though, the label does not preclude first-line use.
Prior to initiating therapy with Tysabri, physicians are to obtain MRI scans on patients to help differentiate potential future MS symptoms from PML.
Tysabri's risk-management plan, dubbed the TOUCH Prescribing Program, is designed to inform physicians and patients of the product's benefits while minimizing its potential PML risks.
Patients must enroll in the program to receive the drug, which will only be prescribed, distributed and infused by prescribers, infusion centers and pharmacies registered with the program. Patients are to be evaluated at three and six months after the first infusion, and every six months thereafter.
"There is a lot of built-in, rapid and immediate follow-up of patients in the program," explained Russell Katz, who works within the FDA's Office of Drug Evaluation. He stressed the program's dual role in educating patients and physicians, as well as informing the companies and regulatory officials about PML infection rates, currently estimated at one in 1,000.
Biogen Idec, of Cambridge, Mass., is compelled to inform the FDA of new PML cases within 15 days.
Adherence to such a rigid risk-management plan was recommended by the FDA's Peripheral and Central Nervous System Drugs Advisory Committee earlier this year. The panel met over two days to contemplate data from Biogen Idec, other findings from the FDA, as well as pro and con arguments from patients, their advocates and physicians. At the time, FDA officials acknowledged the likelihood of future cases of PML and warned against its dire consequences. (See BioWorld Today, March 8, 2006, and March 9, 2006.)
"We don't know how to predict who's going to get it," Katz reiterated, adding that "this is balanced against the significant benefit that we believe the drug confers."
Tysabri initially received FDA approval in November 2004, but was withdrawn by Biogen Idec in February 2005. In addition, all clinical trials were brought to a halt. Such studies resumed this past February.
Galson characterized the re-approval as "very rare."
The principal products used for MS include four disease-modifying therapies: Avonex (beta interferon 1a, also from Biogen Idec), Betaseron (beta interferon 1b, from Berlex Laboratories Inc.), Copaxone (glatiramer acetate, from Teva Pharmaceuticals Inc.) and Rebif (beta interferon 1a, from Serono SA). An immunosuppressant, Novantrone (mitoxantrone, from Serono), also is used.
On Monday, Biogen Idec's stock (NASDAQ:BIIB) fell $2.32 to $45.39. Shares in Dublin, Ireland-based Elan (NYSE:ELN) also traded down, losing $2.46 to close at $16.52, or 13 percent.