Last Updated Oct 27, 2009 12:47 PM EDT
Hard and fast data confirms that from July 2006 (when Tysabri marketing resumed) to September 8, 2009, thirteen worldwide cases of Tysabri-related PML occurred in patients being treated for MS with Tysabri monotherapy. Of these, only four cases were patients in the United States, according to an FDA Post-marketing Drug Safety report.
Germany is an important MS market for Biogen. Aside from the U.S., Europe is home to four of the top seven markets -- Germany, Italy, UK, and Spain -- in terms of commercial dollars spent on disease modifying drugs for use in MS, according to an analysis of the global MS market by the pharmaceutical research outfit Visiongain.
Patients receiving monthly Tysabri infusions in the U.S. must be enrolled in the TOUCH Distribution Program overseen by Biogen, which involves (i) extensive monitoring of all patients for signs of PML and (ii) education of all patients and providers, with strong emphasis communicated to all parties that the drug is contraindicated for use in MS patients taking any drugs that may increase their risk of opportunistic infections, including drugs that lower immune function (e.g., azathioprine, chemotherapy, cyclosporine) or immunomodulators, such as the interferon-based disease-modifying therapies.
Aside from voluntarily enrollment of patients in Biogen's Phase 4 trial, TYGRIS (Tysabri Global Observation Program in Safety), which is a prospective 5-year, 5000-patient cohort observational study to further evaluate PML risk and overall safety of Tysabri therapy, there are few -- if any -- restricted distribution programs in place throughout Europe.
As mentioned, most of the other reported cases of PML are alleged to have occurred in Germany, where oversight is purportedly lax, especially in the monitoring of the presence of latent JC virus and a mandated prior "washout" phase required in patients recently removed from other immunosuppressant therapies, both high-risk factors for development of PML. However, since late summer, German authorities have been working with the company to make sure "appropriate use of Tysabri is monitored and followed up with [patients]," Chief Executive Jim Mullen said on the third-quarter earnings call.
The duration of therapy in the newly diagnosed PML patients is unknown. That said, lax supervision in German -- and other European -- MS treatment facilities could be a contributing risk factor behind the higher incidence(s) and prevalence of reported PML cases.
In the last 12 months, Biogen has engineered relationships between academic reference centers and many of the larger MS clinics in Germany so that the prescribing of Tysabri can occur in a more structured environment -- in compliance with a common protocol developed and published by the Medical Advisory Board of German MS, according to chief operating officer Robert Hamm. To date, 250 top German MS treatment centers are linked to 40 reference centers, he said on the call. This initiative should play out in the company's favor as European regulators re-assess the risk-benefit profile of Tysabri.
Image source: flickr, courtesy of The University of Utah -- Eccles Health Sciences Library