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Testing times for Tysabri

Posted on: 11 Mar 05


Biogen Idec and Elan have announced the voluntary suspension from sale and withdrawal from clinical trials of Tysabri, the companies' novel therapy for the treatment of relapse remitting multiple sclerosis (RRMS). This move has already slashed share prices of both companies. Even if Tysabri is relaunched with some form of black-box warning, doubts will surely linger over its long-term safety.

This decision to withdraw Tysabri (natalizumab) was based on very recent reports of two serious adverse events that occurred in patients treated with Tysabri in combination with Avonex (interferon beta-1a) in clinical trials. These events involve one confirmed, fatal case and one suspected case of progressive multifocal leukoencephalopathy (PML), a rare and frequently fatal demyelinating disease of the central nervous system. Both patients received more than two years of Tysabri therapy in combination with Avonex.


Although the FDA recommended the suspension of the drug, the companies stressed that the final decision was made by the drug makers themselves, and that they would be reconvening with the FDA on March 4, 2005.


The companies' move should be viewed in the context of heightened sensitivity over drug safety in the wake of the COX-II controversy that has enveloped big pharma in recent months. However, any direct comparison between Tysabri and a case such as Vioxx at this stage would be grossly overstating matters: FDA officials have been at pains to stress the difficulties in assessing the precise causes of the disease symptoms seen in the Tysabri case.


Trials put on hold


To date, approximately 3,000 patients have been treated with Tysabri in clinical trials of RRMS, Crohn's disease and rheumatoid arthritis (RA), with no reports of PML in any patients receiving Tysabri monotherapy. Nevertheless, all clinical trials of the drug have been put on hold, including the head-to-head study comparing the safety and efficacy of Tysabri against Rebif - STARS (Study of Tysabri Against Rebif in relapse remitting multiple sclerosis).


As such, recent events will no doubt delay the potential launch of the drug for Crohn's disease and RA by up to two years, while the use of Tysabri in combination with Avonex for RRMS no longer appears to be a commercially viable direction for Biogen and Elan to take.


Tysabri was granted accelerated approval in November 2004, accounting for $3 million in sales for Biogen Idec and $6.4 million for Elan in Q4 2004. Tysabri is a critical drug for both companies and was forecast to be the driving force behind their respective future growth strategies, with Datamonitor having forecast 2010 revenues of the drug to exceed $1.9 billion.


Body blow for manufacturers


The withdrawal has been a huge blow for both companies, with Elan especially likely to suffer in the wake of its brush with bankruptcy in 2002. In response to the news, share prices of Biogen Idec and Elan fell by 43% and 70%, respectively. Contrastingly, those of competitors have risen sharply, with shares of Serono, which co-markets Rebif (interferon beta-1a) in the US rising 20%. Shares in Teva, which sells Copaxone (glatiramer acetate), and Schering AG, which markets Betaseron (interferon beta-1b), also experienced increases.


There are a number of possible future scenarios for Tysabri. The best case scenario, although also the most unlikely, is that there is no link between Tysabri-Avonex combination therapy and PML, resulting in no FDA action being taken. However, the more likely outcome is that that Tysabri receives a strong black-box warning from the FDA for use in combination therapy. The FDA could also choose a couple of other options, such as including a black-box warning for both mono- and combination therapy Tysabri, and the worst case move to withdraw Tysabri permanently.


Working on the most likely scenario of a black-box warning for use in combination therapy only, Datamonitor believes that sales for the monotherapy will resume in Q3 2005 without the need for further clinical trials. Tysabri's strong efficacy could still drive good uptake, and physician confidence will, to a limited extent, be bolstered by the positive two-year Phase III data released earlier in February 2005.


In addition, the once-monthly administration schedule is a strong benefit in terms of patient convenience. Tysabri's high price has minimally affected reimbursement status, according to Biogen, and therefore it should also support sales.


Nevertheless, doubts will inevitably remain over Tysabri's safety, which could substantially impact sales of the monotherapy. In the wider setting, the withdrawal of the drug throws the issue of new product regulation back into the limelight, again highlighting the long and complex journey that new drugs undertake to reach the market.



Related research:


·          Commercial Perspectives: Multiple Sclerosis - How to Find Opportunities in an Unremitting Market

·          Top CNS Portfolios in 2004 - The Industry Gold Standards


Last updated on: 27/08/2010 11:40:18

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