Article: Natalizumab

Natalizumab is a drug co-marketed by Biogen Idec and Élan as Tysabri. It was previously named Antegren. Tysabri is a monoclonal antibody that has proven efficacy in the treatment of two serious autoimmune disorders: multiple sclerosis (MS) and Crohn's disease (CD). In MS, Tysabri was shown to reduce relapses by 66% vs. a placebo. It slowed the progression of disability (as measured by EDSS) by 44%. While it is impossible to compare results across different clinical trials, interferons are generally acknowledged as demonstrating about a 30-35% decrease in relapse rate vs. placebo; and only two drugs have been shown to decrease the progression of disability, but again only by around 20-40%.

The mechanism of action of this drug is believed to involve the inhibition of immune cells from crossing blood vessel walls to reach various tissues, including the brain. While the drug was shown to be powerfully effective for preventing relapses of MS, the companies announced on February 28 2005 that 1 fatal and one non-fatal case of a rare, often lethal brain disease known as progressive multifocal leukoencephalopathy (PML) were found in patients given Tysabri in combination with Avonex. A second PML death was attributed to Tysabri in March of 2005, in a CD patient. That patient had died about a year earlier from what was thought at that time to be a brain tumor, but the diagnosis was subsequently re-evaluated as having been PML. The CD patient who had received 8 doses of Tysabri over an 18-month period had a prior medication history which included multiple courses of immunosuppressant agents.

Tysabri was voluntarily withdrawn from the market after the first 2 confirmed cases, but as of June 6, 2006 has been returned to market with certain restrictions. One restriction is that Natalizumab cannot be combined with Avonex. The drug is also recommend only for cases of MS that have not been resposive to other drugs. Furthermore, Natalizumab is only to be given at authorized infusion centers.

Biogen Idec lost about $8 billion in market capitalization the day the announcement was made. Elan's stock, which had risen like a Phoenix on positive Tysabri data, also collapsed. Natalizumab had promised to be a major earner for the company and continues to be very costly with an annual cost of about $23,500. Tysabri became part of a broader drug safety story in 2005 in the context of Merck's withdrawal of Vioxx, a widely-used anti-inflammatory drug that was associated with an increased risk of heart attacks.

During the summer of 2005, the drug and the two companies garnered a lot of media attention. This included reports of two additional PML cases, which were later discredited.

The companies announced in the fall of 2005 that they had resubmitted it to the US Food and Drug Administration (FDA) and were also resubmitting to the EMEA, for approval in Europe. The FDA granted Tysabri fast track status again in MS. No one debates that Tysabri is an extraordinarily effective drug in slowing MS; the debate is now largely around whether and how the drug can be used safely, and in which patients. The FDA has now reapproved the drug and attempts are made to screen patients for PML in hopes that early removal of the drug may allow revesisal of the drug but PML is not treatable and the symptoms are very similar to MS.

TYSABRI® Pricing TYSABRI® (natalizumab) will be available upon the completion of key activities related to the risk management plan, including finalization of educational and training materials, internal validation of systems based on final FDA requirements and training of internal personnel. As such, Elan and Biogen Idec anticipate TYSABRI will be available in July.

The wholesale acquisition cost is $2184.62 per vial.

Elan and Biogen Idec are committed to making TYSABRI accessible to appropriate patients who may benefit from therapy. To achieve this goal, programs have been developed to assist patients who are uninsured or who require financial assistance. Patients who require financial assistance can receive more information by calling MS ActiveSource at 1-800-456-2255.