US group Biogen Idec and Irish drugmaker Elan Corporation have submitted a supplemental Biologics License Application to the US Food and Drug Administration for their multiple sclerosis drug Tysabri (natalizumab), in an attempt to resuscitate the agent after sales were voluntarily suspended earlier this year on safety concerns [[01/03/05a]].

The companies froze Tysabri sales, as well as all ongoing clinical trials with the agent, just three months after it won US approval [[24/11/04a]], following the report of a patient death due to the rare brain disease PML (progressive multifocal leukoencephalopathy). The firms since reported three confirmed cases of PML, two of which were fatal.

When the news first broke, the group’s share prices were devastated, with Biogen stock tumbling 44% to $37.88 and Elan’s plunging over 70% to $8.07 [[01/03/05a]]. The degree of investor panic was down to the fact that Tysabri was considered as critical to the growth of both companies; the drug had been expected to make peak annual sales of $2.0-$3.0 billion a year by 2007.

Biogen Idec and Elan subsequently launched a comprehensive safety investigation in collaboration with leading experts in PML and MS, evaluating more than 90% of the 2,000 eligible patients from clinical studies by conducting both a neurological exam and a magnetic resonance imaging scan to determine any adverse effects of Tysabri [[09/08/05a]]. No new confirmed cases of PML were identified.

In order to speed up the product’s potential return to market, the drugmakers have requested Priority Review status for the sBLA which, if granted, would result in FDA action around six months from the submission date compared to 10 months for a standard review.

The sBLA consists of final two-year data from the Phase III AFFIRM monotherapy trial and SENTINEL add-on study with Avonex (Interferon beta-1a) in MS, integrated safety assessment of patients treated with Tysabri in clinical trials, as well as a revised label and risk management plan. Biogen Idec and Elan said they are planning to submit a similar data package to the European Medicines Agency as part of the ongoing review process, which was initiated last year.