This Is MS - Tysabri could be ''back on the market by Fall'' | Unbiased Multiple Sclerosis Research, News, and Support Community

March 4th, 2005

A little more detail has emerged on the suspension of Tysabri, which has hit the MS world by storm and left many dazed and confused by the roller coaster ride. To be clear, the cases of Progressive multifocal leukoencephalopathy (PML) have only been seen on those who have spent 2+ years on the combination of Avonex and Tysabri. Nothing of the sort has been seen with Tysabri alone.

What is PML? According to the Cleveland Clinic:

"Progressive multifocal leukoencephalopathy (PML) is an infrequent disorder of the nervous system that primarily affects individuals with suppressed immune systems (including, allograft recipients such as kidney transplant patients; patients with cancers such as leukemia or lymphoma; and nearly 10% of patients with acquired immune deficiency syndrome (AIDS). The disorder, which is caused by a common human polyomavirus, JC virus, is characterized by demyelination or destruction of the myelin sheath that covers nerve cells. The myelin sheath is the fatty covering — which acts as an insulator — on nerve fibers in the brain. Symptoms of PML include mental deterioration, vision loss, speech disturbances, ataxia (inability to coordinate movements), paralysis, and, ultimately, coma reflecting the multifocal distribution of brain lesions. In rare cases, seizures may occur." Basically, PML is a virus that most people (~70%) already have present in their bodies getting out of control due to a malfunctioning/weak immune system. It is a possiblity that the 2 victims in the Tysabri+Avonex trials had other issues besides MS which compromised their immune systems. In such a case, the drug would be reapproved but excluded for these patient subgroups, such as those with HIV. [Update: Biogen/Elan have just stated: "Neither patient had a known history of immunosuppression," so this is no longer a relevant conjecture].

If it can be shown that Tysabri alone is safe, then it might be re-approved relatively quickly. The companies have stated that re-introduction in Fall (Q3, 2005) is likely if no further evidence substantiates continued suspension. They have also stated that the FDA has not asked for the drug to be removed from the market. It is hard not to say it: The need to combine Tysabri and Avonex was never clearly apparent, and certainly not borne out in the trial results where Tysabri alone stood its ground. Sigh.

Whew... what a disgusting day. Our hearts go out to those two victims, and our hopes go out that Tysabri, which brought so much hope to so many, is actually safe and it is the combination of Avonex and Tysabri that is the culprit.

Please click "read more" to see some direct comments from the company regarding the timeline...

Comments from the Companies The companies said the confirmed or suspected PML cases occurred in patients who had been taking Tysabri in combination with Biogen Idec's existing multiple sclerosis drug Avonex for two or more years. There was no evidence of the condition in patients taking Tysabri alone.

The companies, which have also stopped clinical trials of the drug for rheumatoid arthritis and Crohn's disease, said they will be re-examining the brain scans from all patients in previous clinical trials to learn more about what connection, if any, may exist between Tysabri and the development of PML. Jim Mullen, chief executive of Biogen Idec, told investors and reporters on a conference call that it would not take the companies "a long time" to re-evaluate the clinical trials. But he said "it may take some time to figure out a path forward" for the drug.

Elan said on a conference call it does not believe it is the intention of the U.S. Food and Drug Administration to have the drug removed from the market and that if no more cases of PML are found Elan would hope to have Tysabri back on sale by the third quarter of 2005. "I think it's very plausible that in the absence of anything new that we may find that this product would easily be back on the market by the fall," said Kelly Martin, Elan's chief executive.

Tysabri is the first in a new class of multiple sclerosis drugs called selective adhesion molecule, or SAM, inhibitors. It is a humanized monoclonal antibody that blocks a molecule known as alpha-4 integrin and prevents inflammatory cells from escaping into the tissue of the brain.
Source: http://biz.yahoo.com/rb/050228/health_biogen_elan_5.html