Tysabri PML Warning:
Tysabri (natalizumab) is a drug used to treat relapsing multiple sclerosis (MS) and Crohn's disease in adults. Approximately 30,000 patients are currently on Tysabri. Marketed by Biogen Idec and Elan. In 2005 Tysabri (natalizumab) drug was pulled from the market and due to a temporary Tysabri recall after three clinical trial patients developed a rare brain infection called progressive multifocal leukoencephalopathy (PML). From July 2006, (when Tysabri marketing resumed) to September 8, 2009, 13 more reported cases of Tysabri-related PML were confirmed worldwide in patients being treated for MS with Tysabri monotherapy. Of these, four cases were patients in the United States.
Tysabri and Progressive Multifocal Leukoencephalopathy (PML)
A rare viral infection of the brain, PML is a progressive demyelinating disease, meaning that it slowly destroys the myelin sheath surrounding the nerve cells in the brain.Per the FDA Tysabri warning and Tysabri medical studies discussed below, MS patients taking Tysabri are at an increased risk of developing PML. Sadly, most patients with PML die in less than five months after PML appears.
Tysabri and Liver Damage
According to product safety warnings released by the FDA, patients taking Tysabri are at risk of sustaining serious liver damage. Signs of liver damage can appear as early as a week after the first dose of Tysabri; severe liver damage can lead to death or even require a liver transplant.
Updated FDA Tysabri Information: [9/2009]
The FDA continues to receive reports of progressive multifocal leukoencephalopathy (PML) in patients receiving Tysabri. Tysabri was approved by the FDA for the treatment of relapsing forms of multiple sclerosis (MS) in November 2004 and for moderately to severely active Crohn's disease in January 2008. From July 2006, (when Tysabri marketing resumed) to September 8, 2009, 13 reported cases of Tysabri-related PML were confirmed worldwide in patients being treated for MS with Tysabri monotherapy. Of these, four cases were patients in the United States (U.S.). There have been no postmarketing reports of PML in patients treated with Tysabri for Crohn's disease. Less than 2% of Tysabri use in the U.S. has been in patients with Crohn's disease.
The risk for developing PML appears to increase with the number of Tysabri infusions received. The number of monthly infusions of Tysabri in the 13 patients who developed PML ranged from 12 to 35 infusions. The average number of infusions received before the diagnosis of PML was 25. There is minimal experience in patients who have received more than 35 infusions of Tysabri. See more on FDA Tysabri PML warning
The overall rate of developing PML with Tysabri therapy in patients who have received at least one infusion remains below one per 1,000 patients. Based on available data from the U.S. and outside of the U.S., the current rate of PML in patients who have received at least 24 infusions ranges from 0.4 to 1.3 per 1,000 patients.
At this time, the FDA is not requiring changes regarding PML to the Tysabri prescribing information or to the Tysabri risk management plan, called the TOUCH Prescribing Program. All patients receiving Tysabri therapy in the U.S. must be enrolled in the TOUCH Prescribing Program. Under this program, every patient who receives Tysabri is closely monitored for the occurrence of PML and other serious opportunistic infections. Note: There is no current information or plans announced of a FDA Tysabri recall
Current FDA Alert: [issued 8/2008]
The FDA has recently received information from the manufacturer about two new cases of progressive multifocal leukoencephalopathy (PML) in patients receiving Tysabri monotherapy for multiple sclerosis in Europe. Both patients had received Tysabri for more than one year. PML, which is usually fatal, is a known risk of Tysabri treatment, but previous cases in patients with multiple sclerosis were seen in combination with other immunomodulatory therapies. About 39,000 patients have received treatment with Tysabri worldwide, with about 12,000 patients having been treated for at least one year. No new cases have been seen in the US, where about 7,500 patients have received the drug for longer than one year and about 3,300 patients have received the drug for at least one and a half years. Healthcare Professional Sheet
Previous FDA Alert: [issued 2/2006]
The FDA has lifted the clinical hold on Biogen-IDEC's trials of natalizumab for patients with multiple sclerosis (MS). Biogen-IDEC can now resume administration of natalizumab to patients with relapsing-remitting MS who had previously been treated with the drug in clinical trials. Biogen-IDEC had previously suspended marketing of natalizumab and all further dosing of patients in on-going clinical trials. This decision was made after confirmation of one fatal case and one additional case of severely disabling progressive multifocal leukoencephalopathy (PML) in patients receiving natalizumab for MS. A third case of PML, this one fatal, in a patient with Crohn's Disease had been identified shortly thereafter. Healthcare Professional Sheet
Information for Healthcare Professionals - Natalizumab Injection for Intraveneous Use (marketed as Tysabri) - (8/2008)
FDA ALERT [8/2008]: The FDA has recently received information from the manufacturer about two new cases of progressive multifocal leukoencephalopathy (PML) in patients receiving Tysabri monotherapy for multiple sclerosis in Europe. Both patients had received Tysabri for more than one year. PML, which is usually fatal, is a known risk of Tysabri treatment, but previous cases in patients with multiple sclerosis were seen in combination with other immunomodulatory therapies. About 39,000 patients have received treatment with Tysabri worldwide, with about 12,000 patients having been treated for at least one year. No new cases have been seen in the US, where about 7,500 patients have received the drug for longer than one year and about 3,300 patients have received the drug for at least one and a half years.
In the U.S., Tysabri is available only to patients with relapsing multiple sclerosis (MS) or Crohn's disease (CD) who are enrolled in the risk minimization plan called the TOUCH Prescribing Program. Under the TOUCH Prescribing Program, every Tysabri-treated patient is closely monitored and followed for the occurrence of PML and other serious opportunistic infections.
While the two patients who developed PML were on monotherapy, the FDA still believes that Tysabri monotherapy may confer a lower risk of PML than when Tysabri is used together with other immunomodulatory medications.
The FDA is working with the manufacturer to amend the product labeling to inform prescribers and patients that cases of PML have occurred in patients taking Tysabri as monotherapy. Note: There is no current information or plans announced of a FDA Tysabri recall
This information reflects FDA's current analysis of data available to FDA concerning this drug. FDA intends to update this sheet when additional information or analyses become available.
To report any serious adverse events associated with the use of this drug, please contact the FDA MedWatch program, using the contact information at the bottom of this sheet.
Recommendations and Information for Healthcare Professionals registered with the TOUCH Prescribing Program to Consider when Prescribing Tysabri
- The two new cases of PML are notable for being the first cases occurring in the absence of concomitant or recent immunomodulatory therapy (e.g., beta-interferons)
- Although PML and other opportunistic infections are known risks of Tysabri, these are the first cases of PML that have been reported following Tysabri's market re-introduction in June 2006.
- PML is a rare infection of the central nervous system caused by a virus that can affect patients who have a compromised immune system.
- Both of the recently diagnosed patients were receiving Tysabri as monotherapy (one for 14 months and one for 17 months), although one of the patients had a history of prior immunosuppressant therapy with azathioprine and beta-interferons.
- Both patients were diagnosed on the basis of physical findings, MRI findings, and the detection of JC viral DNA in the cerebrospinal fluid.
- The incidence of PML with Tysabri remains unknown, although the available data indicate that the risk of PML when Tysabri is taken as monotherapy is lower than the risk of PML when Tysabri is taken with other immunosuppressant MS treatments.
- Continued clinical vigilance and close monitoring for the signs and symptoms of PML as dictated by the TOUCH Prescribing Program is necessary.
- Tysabri should not be infused if PML is suspected.
Information for Healthcare Professionals and Patients to Consider
- Always talk to your doctor about any medications and over the counter supplements that you may be taking.
- If you and your doctor decide that the benefits of starting Tysabri outweigh possible risks, then you must be enrolled in the TOUCH Prescribing Program before receiving Tysabri. The TOUCH Prescribing Program materials will describe the signs and symptoms of PML you should watch for.
- PML is a rare infection of the brain caused by a polyomavirus, called the JC virus. The JC virus is often acquired during childhood. Most adults have been infected with the JC virus but do not develop PML. The virus appears to remain inactive until something (such as a weakened immune system) allows it to be reactivated and start to multiply. People with a weakened immune system or people taking drugs that suppress their immune system (immunosuppressants) are most likely to get the disease. This virus infects the patient's brain and nervous system when their immune system is not working optimally.
- PML can occur naturally in the course of certain diseases, and it may also occur if someone's immune system has been suppressed by medications. Tysabri is one of the medications that PML has been associated with. Symptoms of PML may be similar to MS, so the diagnosis of PML is made by brain MRI and detection of the virus in the spinal fluid.
- PML symptoms may begin gradually, but they usually worsen rapidly. Symptoms vary depending on which part of the brain is infected. In about two-thirds of patients mental function declines rapidly and progressively, causing dementia. Speaking becomes increasingly difficult. People may become partially blind. Walking may become difficult. Rarely, headaches and seizures occur.
- The two new cases of PML are notable for being the first cases in patients with multiple sclerosis treated with Tysabri who were not also taking beta-interferon therapy.
- Both patients were diagnosed on the basis of physical findings, abnormal MRI findings and the detection of JC viral DNA in the cerebrospinal fluid.
- The risk of developing PML with Tysabri remains unknown, although the available data indicate that the risk of PML when Tysabri is taken as monotherapy is lower than the risk of PML when Tysabri is taken with other treatments that affect your immune system.
- Tysabri should not be given if PML is suspected until further clinical evaluation is performed.Note: There is no current information or plans announced of a FDA Tysabri recall.
Click Here for More Information about Filing a Tysabri Lawsuit: Tysabri PML Lawsuit or call 1-800-883-9858
Background and Data Summary
Tysabri, a recombinant humanized monoclonal antibody that binds to á4-integrin, was initially approved by the FDA in November, 2004, but was withdrawn by the manufacturer in February 2005 after three patients in clinical trials (two in MS trials and one in a CD trial) developed PML. The two MS patients were receiving concomitant beta-interferon therapy, and the patient in the CD trial had received immosuppressive therapy prior to receiving Tysabri.
In June 2006, the FDA approved an application for the re-marketing of Tysabri as monotherapy for the treatment of patients with relapsing forms of MS. Tysabri is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, alternate multiple sclerosis therapies.
In January 2008, Tysabri was approved for inducing and maintaining a clinical response and remission in patients with moderate to severely active CD who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of TNF-á.
The European cases of PML were reported by Biogen Idec and Elan (the makers and marketers of Tysabri) as follows:
- Case 1: This postmarket case of PML occurred in a patient who had received Tysabri monotherapy for 17 months. Prior to treatment, the patient had aggressive MS with high levels of relapse and MRI activity. Signs and symptoms which led to a suspicion of PML included muscle twitching, weakness of the left upper extremity, and brain MRI changes. Tysabri dosing was suspended and the patient underwent cerebrospinal fluid (CSF) testing. The patient has been diagnosed with PML based on the detection of JC viral DNA in the CSF in the setting of these clinical symptoms and MRI findings. Follow up to the case, received by the company on July 31, 2008, reported that this patient is ambulatory and continues to be managed as an outpatient.
- Case 2: This postmarket case occurred in a patient who had received Tysabri monotherapy for 14 months. This patient with MS had a long history of treatment with disease-modifying therapies including azathioprine and beta-interferons. Initial clinical features of PML included development of hemiparesis and cognitive symptoms. Brain MRI revealed lesions that were atypical. The diagnosis of PML was confirmed when JC viral DNA was detected in the CSF in the setting of the appropriate clinical signs, symptoms, and MRI features. At the time of reporting, the patient was hospitalized and in stable condition.
File a Tysabri Lawsuit - Talk to a Lawyer / Attorney