Biogen Idec and Elan Pharmaceuticals informed drug regulatory authorities about two new confirmed cases of PML in individuals who were takingTysabri® (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 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.