Global Insight Perspective | |
Significance | Elan and Biogen have expanded the liver injury safety warning to multiple sclerosis patients. |
Implications | The drug now has liver injury and brain infection warnings in its two U.S. licensed indications, namely multiple sclerosis and Crohn's disease. |
Outlook | Sales of the drug are likely to suffer as multiple sclerosis is Tysabri's main market. Thanks to a more diverse portfolio of innovative drugs, Biogen will not feel the impact as much as Elan. Elan is likely to revise its 2008 guidance downwards and the need for cash could make the Irish biotech a potential takeover target. |
In a letter posted on the U.S. FDA website, Irish biotech the Elan Corporation and Biogen Idec (U.S.) have drawn prescribers' attention to a change in Tysabri's (natalizumab) prescribing information to include a new safety warning. The updated labelling warns doctors that in Phase IV studies, the drug has been linked to "clinically significant liver injury", as shown by an increase in bilirubin and serum hepatic enzyme levels. These abnormal protein and metabolite levels have been detected in some patients as early as six days after treatment initiation. The letter underlines that these symptoms are broadly accepted as early signs of severe liver injury and could, in some patients, result in death or the need for liver transplantation. It adds that these risks should be brought to the patient's attention at the time of prescribing. The updated label recommends that treatment with Tysabri should be stopped if patients display such signs or jaundice.
In effect, the new warning is aimed at neurologists, healthcare professionals and patients that are taking Tysabri in the multiple sclerosis (MS) indication. The drug was first approved in the United States in 2004 for the treatment of MS (see United States: 24 November 2004: Biogen Idec and Elan Score a Hit with MS Approval on One-Year Data). In 2005, the drug was withdrawn from the market after being linked to progressive multifocal leukoencephalopathy (PML)—a rare life-threatening brain disease which killed three patients treated with Tysabri (see World: 1 March 2005: Biogen Idec and Elan Take Body Blows as Tysabri is Pulled from Market). The drug was re-launched in July 2006 but its prescription is strictly regulated through the U.S. TOUCH programme, under which doctors monitor patients for PML, serious opportunistic infections, deaths and discontinuation of treatment. Last month the drug received FDA approval for the treatment of Crohn's disease (CD; see United States - Ireland: 15 January 2008: Elan, Biogen Get FDA Green Light for Tysabri in Crohn's Disease). The labelling information for the treatment of CD includes PML and liver safety warnings.
Outlook and Implications
The extension of a liver safety warning to MS patients does not bode well for the co-marketing partners. After the market re-launch in 2006, the drug's sales were just bouncing back and amounted to US$231.7 million in 2007. Although concerns over liver safety had been raised in the past by the FDA and a related warning was included for Tysabri's prescribing information in the CD indication, the latest label amendment is likely to have an impact on the drug's sales. Despite Tysabri's recent U.S. approval in the CD indication, its market share in this segment is expected to be restricted by the seriousness of the drug's potential side effects (see United States: 22 January 2008: Tysabri's Crohn's Disease Market Potential Remains Limited).As such, MS is the drug's main market and is likely to remain so. A Biogen spokesperson revealed that 1,000 patients were concerned by liver injury. This effectively means that 5% of the patients treated with Tysabri suffered from liver injury (see United States - Ireland: 7 January 2008: Elan, Biogen Release Update on Tysabri in MS). This is a significant figure, which might have prescribers and patients reconsidering if the drug's benefits still outweigh the risks.
The impact is expected to be felt the most by Elan as the Irish biotech has a restricted drug portfolio and relies heavily on Tysabri to bring in revenues. The drug accounts for 51% of Elan's pharmaceutical sales (see Ireland: 13 February 2008: Elan Predicts 30% Revenue Rise in 2008 as 2007 Losses Widen). The company, which expected a 30% rise in revenues this year on the back of bouncing Tysabri sales, is likely to revise its 2008 guidance downwards. This is likely to leave Elan with an expanding cash bleed and a serious need for fresh funds. In the light of the present credit crunch conditions, this could make the Irish biotech a potential takeover target. The impact will be more subdued for Biogen as Tysabri accounts for 11% of the company's total revenues, but that still leaves it heavily reliant on MS treatment Avonex (interferon beta-1a) to bring in revenue. Hopes that Tysabri could again aspire to blockbuster status on the back of encouraging safety data may have just been nipped in the bud.