TYSABRI WARNING! Two New Cases of PML Develop in People with MS Taking Tysabri

[Guest guest]

http://www.nationalmssociety.org/news/news-detail/index.aspx?nid=260Aug 01, 2008Two New Cases of PML Develop in People with MS Taking TysabriBiogen

Idec and Elan Pharmaceuticals informed drug regulatory authorities

about two new confirmed cases of PML in individuals who were taking Tysabri® (natalizumab)

as a monotherapy (not in combination with other therapies). 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.

Background: 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 the United States, the drug is available only through a risk

management program called TOUCH, and is only available through doctors

and infusion sites enrolled in the program. The program is designed to

monitor patients for possible signs of PML and other serious

opportunistic infections. Separate risk management plans are also in

place in individual countries in Europe.

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 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.

The National MS Society is proud to be a source of information about

MS. Our comments are based on professional advice, published experience

and expert opinion, but do not represent individual therapeutic

recommendation or prescription. For specific information and advice,

consult your personal physician.