Global Insight Perspective | |
Significance | Elan and Biogen have announced that a fourth multiple sclerosis (MS) patient receiving Tysabri (natalizumab) monotherapy has been diagnosed with Progressive Multifocal Leukoencephalopathy (PML). |
Implications | Although this is the fourth report of PML cases in the span of five months, the disease's incidence rate remains within that mentioned on Tysabri's labelling information. Although this could dent patients' and prescribers' confidence in the drug, the fact is that treatment alternatives are thin on the ground and close patient monitoring has so far prevented casualties. |
Outlook | The present announcement is not expected to result in the drug's market withdrawal or stronger warnings. Nevertheless, it is likely to have repercussions on the drug's sales performance and investors' confidence. To add salt to the wound, an alternative MS treatment with a potentially cleaner safety profile could reach the market in 2010. |
Marketing partners Biogen Idec (U.S.) and Elan Corporation (Ireland) have announced that their multiple sclerosis (MS) drug Tysabri (natalizumab) was linked to a new case of Progressive Multifocal Leukoencephalopathy (PML) in a European patient who had been treated with Tysabri monotherapy for 26 months, reports The Wall Street Journal. This makes it the fourth Tysabri-associated PML case since the summer. PML is a potentially deadly brain disease.
During the summer, two Tysabri-treated MS European patients were reported to have developed PML. Those two patients had been treated with Tysabri for 14 and 17 months. One patient was MS-treatment naïve while the other had received other disease modifying drugs before being switched to Tysabri monotherapy. At the end of October, a third Tysabri-associated PML case was reported in an American patient who had been receiving treatment for 14 months.
This is not the first time that Tysabri finds itself in the hot seat as the drug was withdrawn from the market in 2005 after it was linked with three cases of PML, two of which were fatal (see World: 1 March 2005: Biogen Idec and Elan Take Body Blows as Tysabri is Pulled from Market). The drug was re-introduced to the market in July 2006. In the United States, its prescription is now strictly regulated through the U.S. TOUCH programme, under which doctors monitor patients for PML, serious opportunistic infections, deaths and discontinuation of treatment. In Europe, although there is no such prescribing programme, doctors are closely monitoring patients taking Tysabri.
Tysabri has seen strong patient uptake upon its market return. There are currently 35,500 patients taking the drug worldwide. The medicine is indicated in patients with highly active relapsing remitting MS who have inadequately responded to, or cannot be treated with, alternative therapies. In clinical trials, Tysabri was shown to decrease bouts of relapses by 68%, a performance superior to rival treatments that roughly result in a 30% decrease. In addition, in a two-year clinical study 17% of Tysabri-treated patients experienced a worsening of their symptoms compared to 29% of placebo-treated patients.
Outlook and Implications
Although this fourth report of PML will not be welcome by Elan and Biogen, it is still unlikely to result in regulatory action. Indeed, the PML incidence is still within that stated on the drug's labelling information. Elan and Biogen estimate the risk of Tysabri-associated PML at 1 per 1,000 in the first 18 months of treatment. Furthermore, the drug's label was recently strengthened to further draw prescribers' and patients' attention onto this fact (see United States - Ireland: 26 September 2008: EMEA Advises Elan, Biogen to Update MS Drug Tysabri Label to Increase PML Risk Awareness and United States – Ireland: 27 August 2008: Heat Cools for Elan, Biogen as FDA Hints at Modest Tysabri Label Changes).
The repercussions for the two companies are therefore mostly expected to be in terms of sales volumes and investor confidence. Although patients and prescribers are still likely to think that Tysabri's benefits outweigh the drug's risks, as it stands, the PML occurrences that happened over the summer seem to have somewhat curbed the drug's sales growth in the third quarter of the year. Indeed at the end of June 2008, Tysabri had garnered quarterly sales of US$200 million, which represented a 25.2% rise in revenues on the first quarter of the year while at the end of September 2008, the drug had generated sales of US$237 million, an 18.5% rise on the second quarter. In terms of patients, the number of Tysabri-treated patients did not grow as fast over the course of the third quarter either. While the number of Tysabri treated patients stood at 26,100 at the end of March 2008, they rose to 31,800 at the end of June 2008 and 35,500 at the end of September 2008. This represents a quarter-on-quarter increase of 5,700 and 3,700 patients. If sales start to slump, Elan will be vulnerable in the present market conditions as the Irish biotech is reliant on Tysabri's sales to drive growth. Elan has already announced cost-cutting measures in order to pledge all the funds it can towards its pipeline (see Ireland: 12 December 2008: Elan Announces Cuts, Redirects Funds Towards Pipeline).
Biogen has nevertheless re-iterated its forecast of 100,000 patients to receive Tysabri by 2010. One of the downsides for the two companies is also that it was suggested that combination therapy between Tysabri and other MS treatments was at the root of the initial 2005 PML cases. As a result, the drug is now prescribed as a stand-alone treatment but the present occurrence of PML in a patient on Tysabri monotherapy casts doubt over the alleged link. On the upside, patient monitoring and plasma exchange have so far this year prevented fatalities.
Tysabri for now benefits from its improved efficacy profile over traditional MS treatments. The drug also is indicated in patients that are left with few treatment options. Those two factors have contributed to its market performance. Elan and Biogen will nevertheless be mindful that competition looms in this field. Indeed Swiss pharmaceutical company Novartis is consistently touting its own MS candidate treatment FTY720 (fingolimod), which seems to have an improved efficacy and safety profile (see Switzerland: 12 December 2008: Novartis's MS Drug FTY720 Fares Better than Interferon in Phase III Study). On top of its cleaner slate, FTY720 also benefits from its oral formulation over Tysabri, which requires monthly injections. Novartis intends to file FTY720 for regulatory submission in both Europe and the United States by the end of 2009.