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A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases
Date: Fri 29 Oct 2010
Source: Nasdaq, Dow Jones Newswires [edited]
Biogen Idec Inc. (BIIB) disclosed 2 more cases of a rare brain
infection in multiple sclerosis patients on Tysabri, which it sells
with Elan Corp. (ELN), bringing the total number of cases to 70 as of
Fri 1 Oct 2010. [Tysabri (Natalizumab) is a humanized monoclonal
antibody against the cellular adhesion molecule Eo4-integrin.
Natalizumab is used in the treatment of multiple sclerosis and
Crohn's disease. Further information can be obtained from the
Natalizumab (Tysabri) Fact Sheet:
The Weston, Mass., biotech company reported that there have been no
additional deaths among patients that have developed the infection --
known as progressive multifocal leukoencephalopathy, or PML -- a
number that stands at 14.
Sales of Tysabri are important to the future of both Elan and Biogen.
The drug is considered a highly effective therapy for multiple
sclerosis, but its growth has been slower than originally hoped due
to concerns about the risk of PML that led to the drug's temporary
withdrawal beginning in 2005.
The multiple sclerosis market is getting increasingly competitive,
something that Wall Street believes could put some pressure on
Tysabri. Novartis AG's ( NVS) Gilenya, the 1st oral therapy for the
disease, was recently approved, and numerous other therapies are in
development.
Biogen is scheduled to report its 3rd-quarter result on 26 Oct 2010,
when it will update patient numbers.
The overall global PML rate is about 0.91 per 1000 patients, the
company said, which falls within the one-in-1000 rate previously seen
in clinical trials and implied on the drug's label.
As of 30 Jun 2010, 52 700 patients were using the drug around the
world. In total, about 71 400 patients have used the drug since its
launch. Of the total PML cases, 29 were in the U.S., 37 were in the
European Union and 4 were in other areas.
The number of cases is important, because if the infection rate
climbs too high, the drug's sales growth may drop. Regulators have
said that they watch the cases but have concluded that the benefits
of the medicine to MS patients outweigh the risks.
The risk of the infection increases with the number of monthly
infusions that a patient receives. The incidence rate appears to drop
after 30 months of use, but Biogen views the drop as inconclusive,
because there aren't enough patients to have confidence in that finding.
The most recent data update translates to a rate of 1.42 cases per
1000 for patients on the drug for a year or longer, but rises to 1.87
per 1000 for those on the drug for 2 years or longer.
Looked at another way, the rate is about 1.44 cases per 1000 patients
on the drug for between 2-3 years. The incidence is about 0.38 case
per 1000 patients in those using it for 1-2 years, and it is
essentially nonexistent in patients using it for less than a year.
[Byline: Thomas Gryta]
--
Communicated by:
T J Allen
[Progressive multifocal leukoencephalopathy (PML) is caused by the
reactivation of a common virus in the central nervous system of
immune-compromised individuals. JC Polyomavirus (often called JC
virus, JC being the initial of the 1st PML patient [and not to be
confused with Jamestown Canyon virus, an orthobunyavirus - Mod.DK])
is carried by a majority of people and is harmless except among those
with lowered immune defenses. The disease occurs, rarely, in organ
transplant patients, people undergoing chronic corticosteroid or
immunosuppressive therapy, and individuals with cancer, such as
Hodgkin's disease, lymphoma, and sarcoidosis. PML is most common
among individuals with acquired immune deficiency syndrome (AIDS).
Studies estimate that prior to effective antiretroviral therapy, as
many as 5 percent of people with AIDS eventually developed PML. For
them, the disease was most often rapidly fatal. As described above,
PML is being observed now in a minority of patients undergoing
prolonged therapy for multiple sclerosis.
The symptoms of PML are the result of an infection that may cause the
loss of white matter (which is made up of myelin, a substance the
surrounds and protects nerve fibers) in multiple areas of the brain.
Without the protection of myelin, nerve signals can't travel
successfully from the brain to the rest of the body.
Typical symptoms associated with PML are diverse, since they are
related to the location and amount of damage in the brain, and evolve
over the course of several days to several weeks. The most prominent
symptoms are clumsiness; progressive weakness; and visual, speech,
and sometimes, personality changes. The progression of deficits leads
to life-threatening disability and death over weeks to months.
A positive diagnosis of PML can be made on brain biopsy, or by
combining observation of a progressive course of the disease,
consistent white matter lesions visible on a magnetic resonance image
(MRI) scan, and the detection of the JC virus in spinal fluid. For
further information concerning PML, see: NINDS Progressive Multifocal
Leukoencephalopathy Information Page:
JC polyomavirus is a human virus with a circular double-stranded DNA
genome that is genetically similar to another human virus, BK
polyomavirus virus, and to the well known laboratory virus, Simian
virus 40 (SV40). JC polyomavirus was discovered in 1971 and named
after the initials of a patient with progressive multifocal
leukoencephalopathy. The virus causes PML and other diseases normally
only in cases of immunodeficiency, such as in AIDS or during
treatment with drugs intended to induce a state of immunosuppression
(e.g. organ transplant patients). The above report reaffirms that
there is risk of activation of latent JC polyomavirus infection by
prolonged treatment with Tysabri in the treatment of multiple
sclerosis. This poses a unwelcome dilemma for both multiple sclerosis
patients, the regulatory authorities and the pharmaceutical industry. - Mod.CP]
[see also:
1998
----
Simian viruses, potential for human infection (04) 19980414.0684]
..................................................cp/msp/dk
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Posts
The risks for contacting PML vary based on several factors, like previous treatments with other drugs, JCV antibody test results and length of treatment. In worst case scenarios the the risk for PML can be as high as 1 in 125. Considering that there are hardly any effective progressive multifocal leukoencephalopathy treatments this information should be weighted accordingly.
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