Biogen Idec and Elan Pharmaceuticals
informed drug regulatory authorities about two
new confirmed cases of PML(progressive multifocal
leukoencephalopathy) in individuals who were
taking Tysabri® (natalizumab) as a monotherapy
(not in combination with other therapies).
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Medical Update Memo
August 12, 2008
SUMMARY
PML (progressive multifocal leukoencephalopathy)
is a viral infection of the brain that usually
leads to death or severe disability. Although FDA
prescribing information includes a black box warning
about the risk of PML, the three previous cases
of PML that occurred in the context of clinical
trials were in patients who had taken Tysabri in
association with other immune-modulating or immune-suppressing
medications.
DETAILS
The companies held a conference call for prescribers
and investors to provide details about the two
cases, both of which occurred in European males.
One had received Tysabri as a first line therapy
because of the aggressive nature of his disease,
and had been on Tysabri alone for 17 months before
developing a slowly progressive focal twitching
and weakness in one arm. Brain MRI showed a non-typical
lesion but his spinal fluid was negative for JC
virus until it was done a second time. He received
five courses of plasma exchange and is currently
stable and at home.
The second case has been reported to be a male
who had received immune-suppressing and immune-modulating
therapies in the past. He used Tysabri alone for
14 months before developing weakness on one side
of the body. Despite treatment with steroids his
symptoms progressed and included cognitive changes.
His MRI was not typical for MS, and spinal fluid
was positive for JC virus. He is reported to be
hospitalized and is slated to receive plasma exchange
therapy.
Tysabri is a laboratory-produced monoclonal antibody.
It is designed to hamper movement of potentially
damaging immune cells from the bloodstream, across
the "blood-brain barrier" into the brain
and spinal cord. It has been shown to be effective
in reducing the risk of disability progression
and exacerbations (relapses). In Canada, the Tysabri
Care Program is offered to help educate patients
and health care professionals about the benefits
and risks of Tysabri use prior to treatment. The
companies recently reported that nearly 32,000
patients have been dosed with Tysabri. Of those,
nearly 14,000 have been on the drug for at least
12 months, and 6,600 have been on the drug for
at least 18 months. Up to this time there have
been no previous confirmed cases of PML in patients
using the drug as monotherapy. Recent, small-scale
studies supported by Biogen Idec have investigated
the use of plasma exchange, a blood-cleansing treatment,
to clear the bloodstream of Tysabri in the event
of PML, for which there is no established therapy.
The studies suggested that plasma exchange could
indeed clear much of the drug from a person's bloodstream,
but it was not possible to determine experimentally
whether that would lead to a reduction of PML symptoms.
Comment
These incidents of PML are unfortunate and disappointing,
and we hope for the best possible outcomes for
these individuals and their families. However,
their occurrence is within range of the predicted
frequency of PML cases, estimated by a published
report and by the FDA, of approximately 1 in 1,000
people taking the drug. "We are encouraged
that the risk management plans in place for early
surveillance, such as the TOUCH program in the
U.S., are doing the intended job of identifying
possible cases of PML early so that patients can
be treated quickly," said John R. Richert,
MD, executive vice president of research and clinical
programs at the National MS Society . "It
will be important to observe whether plasma exchange
therapy in these new cases will have an ameliorating
effect on their PML." These incidents highlight
the need for individuals taking Tysabri to be sensitive
to any occurrence of new, unusual symptoms and
to contact their prescribing physician or infusion
nurse immediately if they occur. Signs of PML may
include any new or worsening neurological symptoms
such as any changes in thinking, eyesight, balance,
strength and other symptoms.
Tysabri is a registered
trademark of Biogen Idec and Elan.
With information from the National MS Society (USA)
National Client Services
Medical Information and Education
Offert en français.
Disclaimer
The Multiple Sclerosis Society of Canada is an independent, voluntary health
agency and does not approve, endorse or recommend any specific product or therapy,
but provides information to assist individuals in making their own decisions.
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