- Use of Biomarker has Potential to Advance Personalized Treatment
for MS Patients -
WESTON, Mass. & DUBLIN--(BUSINESS WIRE)--May. 17, 2012--
Idec (NASDAQ: BIIB) and Elan
Corporation, plc (NYSE: ELN) today announced that the New England
Journal of Medicine published research from the companies’ global
risk management program that updates the risk of TYSABRI®
(natalizumab)-associated progressive multifocal leukoencephalopathy
(PML), an infrequent but serious brain infection that usually leads to
death or severe disability, in people with multiple sclerosis (MS). The
analysis looked at three risk factors associated with a patient’s PML
risk: anti-JC virus (JCV) antibody status, use of immunosuppressant (IS)
therapy prior to TYSABRI initiation, and longer duration of treatment
Biogen Idec and Elan developed the quantitative risk stratification
algorithm to help physicians and people with MS have more confidence in
their treatment decisions when considering TYSABRI, a highly effective
treatment for relapsing forms of MS.
“By identifying these risk factors and incorporating them into our risk
stratification algorithm, we bring the advantages of personalized
medicine to MS,” said Alfred Sandrock, M.D., Ph.D., senior vice
president, development science and chief medical officer, Biogen Idec.
“This approach to treatment is intended to help patients better
understand their individual benefit-risk profiles when considering
TYSABRI as a treatment option.”
About the Research
Researchers used data from clinical
studies, post-marketing sources, and an independent Swedish registry to
estimate the incidence of PML among TYSABRI-treated patients. Data as of
Feb 29, 2012 from 212 confirmed cases of PML among 99,571
TYSABRI-treated patients were used to develop a risk stratification
algorithm based on three established risk factors for PML: anti-JCV
antibody status, prior use of IS therapy, and duration of treatment with
TYSABRI (one to 24 months vs. 25 to 48 months). Based on the presence or
absence of these risk factors, patients were divided into distinct
subgroups at lower or higher risk for the development of PML.
Blood samples from 5,896 MS patients who participated in three clinical
studies - AFFIRM , STRATIFY-1, and the U.S. arm of the TYSABRI Global
Observational Program in Safety [TYGRIS] study - as well as blood
samples from patients included in the Swedish Multiple Sclerosis
registry, were tested for anti-JCV antibodies.
In addition, data from 54 TYSABRI-treated patients who developed PML and
had blood samples collected six to 187 months before they were diagnosed
with PML were tested for anti-JCV antibodies; all samples tested
positive for anti-JCV antibodies.
Data on prior IS use were not available for all patients taking TYSABRI.
Therefore, the proportion of prior IS use within the global TYGRIS
studies (U.S. and Rest of World) were used to estimate prior IS use in
the overall TYSABRI-treated population.
The risk of PML increased with longer duration of
TYSABRI treatment, with the greatest increase observed after two years
of therapy. Data beyond four years of therapy were limited.
Prior IS use was more common in patients who developed PML (34.5%)
compared to patients in the global TYGRIS study (20.3%), indicating that
prior IS use was associated with an increased risk of PML.
The prevalence of anti-JCV antibodies in the general MS population was
54.9 percent (95% confidence interval [CI], 53.7 – 56.2) and differed
from the 100 percent anti-JCV antibody positivity observed in the 54 MS
patients who developed PML and had known pre-PML anti-JCV antibody
status. Because all 54 MS patients with known pre-PML anti-JCV antibody
status tested positive, a sensitivity analysis assuming one hypothetical
anti-JCV antibody negative PML patient was used to estimate the PML risk
in antibody negative patients.
Anti-JCV antibody status, combined with prior IS use and TYSABRI
treatment duration were used to stratify patients at lower or higher
risk for the development of PML. There was an approximately 120-fold
difference between patients in the lowest and highest risk groups.
Patients who were anti-JCV antibody negative were at the lowest risk for
PML with an estimated risk of 0.09 cases or fewer per 1,000 patients
(95% CI, 0 to 0.48).
The highest risk of PML was found in patients who had received 25 to 48
months of TYSABRI treatment, had been treated with an IS therapy before
TYSABRI treatment was initiated, and were positive for anti-JCV
antibodies. The PML incidence in this group was estimated to be 11.1
cases per 1,000 patients (95% CI, 8.3 to 14.5).
The authors concluded that data from prospective studies are needed to
further characterize these risks.
“Although TYSABRI has proven efficacy, the risk of PML has been a cause
of concern for patients," said Ted Yednock, head of global research at
Elan. "This analysis illustrates how the risk stratification model we
have developed with Biogen Idec can help physicians and MS patients make
more informed treatment decisions."
About the Risk Stratification
The TYSABRI U.S. label and EU
Summary of Product Characteristics were updated to add anti-JCV antibody
status as a risk factor for PML. In addition to prior IS therapy and
duration of TYSABRI therapy, anti-JCV antibody status is the third
factor in the risk stratification model developed by Biogen Idec and
Elan that helps identify a patient’s risk for developing PML. Physicians
can determine their MS patient’s anti-JCV antibody status by using the
STRATIFY JCV assay, the first blood test to be market authorized for the
qualitative detection of antibodies to the polyomavirus JC virus.
At the time of this analysis (February 29, 2012), more than 99,500
patients had been treated with TYSABRI and there were 212 confirmed
cases of PML (2.1 cases per 1, 000 patients).
TYSABRI is approved in more than 65 countries.
TYSABRI is approved in the United States as a monotherapy for relapsing
forms of MS, generally for patients who have had an inadequate response
to, or are unable to tolerate, an alternative MS therapy. In the
European Union, it is approved for highly active relapsing-remitting MS
(RRMS) in adult patients who have failed to respond to beta interferon
or have rapidly evolving, severe RRMS.
TYSABRI has advanced the treatment of MS patients with its established
efficacy. Data from the Phase 3 AFFIRM trial, which was published in the
New England Journal of Medicine, showed that after two years, TYSABRI
treatment led to a 68 percent relative reduction (p<0.001) in the
annualized relapse rate when compared with placebo and reduced the
relative risk of disability progression by 42-54 percent (p<0.001).
TYSABRI increases the risk of progressive multifocal leukoencephalopathy
(PML), an opportunistic viral infection of the brain, which usually
leads to death or severe disability. Infection by the JC virus (JCV) is
required for the development of PML and patients who are anti-JCV
antibody positive have a higher risk of developing PML. Factors that
increase the risk of PML are presence of anti-JCV antibodies, prior
immunosuppressant use, and longer TYSABRI treatment duration. Patients
who have all three risk factors have the highest risk of developing PML.
Other serious adverse events that have occurred in TYSABRI-treated
patients include hypersensitivity reactions (e.g., anaphylaxis) and
infections, including opportunistic and other atypical infections.
Clinically significant liver injury has also been reported in the
post-marketing setting. A list of adverse events can be found in the
full TYSABRI product labeling for each country where it is approved.
TYSABRI is marketed and distributed by Biogen Idec Inc. and Elan
Corporation, plc. For full prescribing information, including boxed
warning and important safety information, and more information about
TYSABRI, please visit www.biogenidec.com
About Biogen Idec
Through cutting-edge science and medicine,
Biogen Idec discovers, develops and delivers to patients worldwide
innovative therapies for the treatment of neurodegenerative diseases,
hemophilia and autoimmune disorders. Founded in 1978, Biogen Idec is the
world’s oldest independent biotechnology company. Patients worldwide
benefit from its leading multiple sclerosis therapies, and the company
generates more than $5 billion in annual revenues. For product labeling,
press releases and additional information about the company, please
Elan Corporation, plc is a neuroscience-focused
biotechnology company committed to making a difference in the lives of
patients and their families by dedicating itself to bringing innovations
in science to fill significant unmet medical needs that continue to
exist around the world. Elan shares trade on the New York and Irish
Stock Exchanges. For additional information about Elan, please visit www.elan.com.
Source: Biogen Idec and Elan Corporation, plc
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