For those that have not been actively tracking developments on Tysabri (known generically as natalizumab and co-owned by BiogenIdec and Elan), the story essentially begins when the drug was approved for use in MS patients in November of 2004. It was met with great fanfare, due to its...

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... remarkable trial results, relatively meager side effect profile, and its once-per-month IV administration. Just as it was beginning to take hold, it was suddenly recalled from the market in early 2005 after 3 patients exposed to Tysabri-- 2 of them in the multiple sclerosis trials, the other in a trial for Crohn's disease-- developed a brain infection called progressive multifocal leukoencephalopathy (PML).

PML is a devastating disease that is almost inevitably fatal, so the extreme reaction was commensurate with the, at the time highly speculative, level of risk. Indeed, two of those patients passed away, providing a stark reminder us that our desire for wonder drugs that cure serious illness but inflict no collateral damage, as Tysabri had been oft idealized, is almost always a dream not supported by reality.

Panic-oriented predictions that Tysabri would never again see the light of day then circulated, preying upon the dearth of information and the frightening specter of a PML infection suddenly developing in an otherwise generally healthy RRMS patient. The MS PML infections had something in common-- co-administration with strong immunomodulators, including Avonex. In other words, Tysabri administration by itself could not be tied directly to the development of PML in the Multiple Sclerosis trials. However, in the Crohn's trials, the patient was found to be truly on Tysabri alone at the time of PML diagnosis, leading the New England Journal of Medicine to conclude that "anti–4-integrin therapy can result in JC virus–induced PML."

A thorough review of practically all Tysabri-exposed patients, including those who had taken it for Crohn's disease and Rheumatoid Arthritis, found no additional cases of PML. With the imperfect information available, the most aggressive estimate of PML risk was made at 1 in 1000, not accounting for co-administration with other immunomodulators. The only way to refine that data was to re-initiate dosing in a controlled trial environment, which the FDA allowed in February of 2006.

With all then-available information in hand, the FDA held an Advisory Committee meeting in March 2006 to decide whether Tysabri should be re-introduced. In an unprecedented move, the meeting was extended an additional day to allow testimonies directly from patients, who in often moving fashion literally begged for the drug to be made available with informed consent.

The Advisory Committee broadly recommended reapproval of Tysabri, even, in what many considered a surprise, as a first-line therapy. They also agreed with the creator's desire to create a stringent patient monitoring program to ensure that any cases of PML would be caught early, given that the risk still was (and is) not fully identified without further data. The issue was passed back to the FDA, which usually follows the instructions of its advisory committees, for final approval.

Just as the drug was seemingly about to be re-introduced, the FDA alerted that it needed additional time to process the application, with a deadline of June 2006. And here we now are, with Tysabri expected to return to the market in July 2006.

At This is MS, we applaud the availability of another therapy option for patients suffering from multiple sclerosis. While Tysabri carries with it a significant level of unknown risk, its benefit profile has been extensively documented, both trough clinical trials involving nearly 8000 patients, as well as anecdotally as demonstrated at the advisory committee meeting. MS'ers, by definition, live their daily lives with an outrageous level of uncertainty, and knowing that there's another weapon they can turn to if their circumstances justify it is a wonderful step forward.

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