|>>Brain Infections From Biogen, Elan MS Drug Continue To Rise|
Last update: 8/19/2010 4:08:27 PM
By Thomas Gryta
Of DOW JONES NEWSWIRES
NEW YORK (Dow Jones)--The incidence of a rare brain infection in patients taking multiple sclerosis drug Tysabri, sold by Biogen Idec Inc. (BIIB) and Elan Corp. (ELN), is continuing to climb, raising concerns about the drug's future.
The drug is considered highly effective and is important to the future of both companies, but its growth has been disappointing because of its link to progressive multifocal leukoencephalopathy, or PML, that led to temporary market withdrawal in 2005.
Data from clinical trials of the drug suggest that PML occurs in one in 1,000 patients, a rate that has been included on its label.
The overall PML rate remains below that level, but it continues to creep higher and numerous measures that correlate with the amount of time spent on the drug show that the rate is exceeded. On Wednesday, the company disclosed five more PML cases, bringing the total to 63 since its relaunch in 2006.
The U.S. Food and Drug Administration monitors PML infections and assesses the related risk "on an ongoing basis to determine the need for any regulatory actions," spokeswoman Sandy Walsh said. The agency will consider label updates and/or additional safety updates as it reviews cases and identifies other relevant information.
"What is in the drug's label now reflects what we know about the incidence data--it would be too speculative to make conclusions about the trends right now," Walsh said Thursday.
Biogen spokeswoman Kate Weiss said the company is constantly in discussions with regulators, but declined to comment further on those talks. She noted that the company is aware of the rising incidence trend.
"Obviously it is something that we are looking into," she said.
PML is caused when the JC virus attacks the central nervous system in people with weakened immune systems, often leading to an irreversible decline in neurologic function and, in some cases, death.
The overall incidence data, including all patients that have used the drug, has been steadily rising and now shows that PML occurs in 0.85 per 1,000 Tysabri patients, as of Aug. 4, a number that stood at 0.47 as of a January update.
For patients using the drug more than a year, the rate now stands at 1.35 per 1,000. But the confidence interval, a statistical tool that helps show the precision of a measurement, shows that there is a 95% probability that the risk is between 1.04 and 1.73 per 1,000 patients. A similar situation--the lower end of the confidence interval being above 1--also occurs in those on the drug longer than 18 months and 24 months, strongly suggesting that the rate is above 1 in 1,000 in those measurements.
The increased risk of the infection with longer use of the drug is included in the drug's label, but Barclay analyst Jim Birchenough warns that the rising case numbers could create "still greater tentativeness in prescribing." Furthermore, it could increase the use of so-called drug holidays--when patients are temporary removed from the drug with the intention of reducing risk--and it could encourage those holidays to come earlier in treatment.
For patients getting 30 months of therapy or more, the incidence of the infection is 1.4 per 1,000 patients, a drop when compared with earlier duration measurements. This drop is even larger for those on the drug longer than 36 months.
But Biogen views the drop as inconclusive, because there aren't enough patients to have confidence in determining that the finding is real.
"We need to see more patient data," she said.
Barclays's Birchenough echoed the sentiment that the data beyond 24 months of therapy is "relatively small."
There is no way to determine what the data from the longer durations will eventually show, but the incidence at earlier durations was once well below the levels now seen in the longer durations, suggesting that they could catch up. They could also show that risk peaks at a certain point in using the drug.
Analysts are concerned about the trends because Tysabri is being sold in a increasingly competitive MS-treatment market and its side-effect profile could make alternatives more attractive.
There is concern that Tysabri use will decline if Novartis AG (NVS, NOVN.VX) gets approval for Gilenia, the first oral MS treatment, which should get a decision from the FDA in September. Meanwhile, several other companies are developing oral therapies for the disease.
Deutsche Bank analyst Robyn Karnauskas recently projected that Tysabri's patient discontinuation rate, currently 2% to 3%, will skyrocket when oral therapies are available. She projects 20% of patients on the drug will stop using it in 2011 and 25% in 2012.
She also expects that fewer patients will begin using Tysabri, as the new options are available, and projects U.S. Tysabri sales declining 40% from $633 million in 2010 to $376 million in 2015.
-By Thomas Gryta, Dow Jones Newswires; 212-416-2169; firstname.lastname@example.org<<