PML News

Man on Ruxolitinib Develops PML

The drug ruxolitinib, used to treat intermediate or high risk myelofibrosis, has been associated with the development of progressive multifocal leukoencephalopathy (PML) in a 75-year-old man. It is not clear whether ruxolitinib caused the PML. (An association does not necessarily mean there is a cause and effect.)

PML is a potentially fatal condition in which the white matter insulating the nerve cells in the brain is destroyed. Myelofibrosis is a bone marrow cancer in which the marrow, where the body makes blood cells, is replaced by scar tissue.

Ruxolitinib is prescribed to treat myelofibrosis. Other treatments for myelofibrosis are stem cell or bone marrow transplants. The disease is rare, occurring in 16,000 to 18,500 patients in the U.S. Ruxolitinib is made by Incyte and sold as Jakafi in the U.S. It is sold elsewhere in the world as Jakavi and is made by Novartis.

Independent investigators are trying to determine if the drug did cause the PML.

A possible link between Jakafi and PML could slow the use of the medication, although a diagnostic test might exclude patients prone to the disease from taking it. This would allow the remainder of patients eligible to take it.

The U.S. Food and Drug Administration (FDA) approved ruxolitinib in November 2011. It was approved in Europe in August 2012. Analysts, who assess the potential for sale of the drug, say other future uses of the drug in patients such as those with polycythemia vera, essential thrombocythemia, and solid tumors could make it a “blockbuster.”

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If you or someone you love is suffering from the effects of PML, you may qualify for compensation if it is linked to medication use. To learn more, contact our PML lawyers today.

Preliminary Data Show Catching PML Early May Prevent Death

If patients with progressive multifocal leukoencephalopathy (PML) are diagnosed using magnetic resonance imaging before symptoms of the disease appear, their chances of survival are much greater than those of patients who are not diagnosed until their symptoms become evident, a preliminary study suggests.

The data were collected by Dong-Si and colleagues, researchers at the biotechnology firm Biogen Idec. The information will be presented as an abstract at the annual meeting of the American Academy of Neurology, scheduled to begin March 16 in San Diego.

Biogen Idec is a drug developer and manufacturer that makes treatments for neurodegenerative (of the brain and nerve tissues) diseases, hemophilia and autoimmune disorders. Among the drugs they make are multiple sclerosis (MS) medications Avonex and Tysabri.

The study’s authors cautioned that the data and conclusions should be considered preliminary until they are published in a peer-reviewed journal.

PML is a severe inflammation of the white matter of the brain. It occurs when the JC virus (polyomavirus JC), which lies dormant in most people except for those with a deficient immune system, is activated. The rare disease occurs in people:

  • Undergoing corticosteroid or immunosuppressive treatment for organ transplantation
  • With certain cancers such as Hodgkin’s disease or lymphoma
  • With autoimmune conditions, including some patients with multiple sclerosis, rheumatoid arthritis, and system lupus erythematosus, when they are treated with biological therapies that reactivate the latent JC virus.

PML usually is fatal in 30 to 50 percent of patients within the first few months after they are diagnosed. This depends upon how severe the underlying disease is and what treatment a patient receives.

One of Biogen Idec’s products is Tysabri (natalizumab), which is an MS medication and is associated with PML.

While the symptoms of PML are many, the most prominent are:

  • Clumsiness
  • Progressive weakness
  • Changes in vision, speech and personality

The study by the Biogen Idec researchers indicated that before these symptoms appeared, all patients who were diagnosed using MRI were alive a year later. In contrast, almost a quarter of PML patients who were not diagnosed until symptoms occurred died.

Biogen Idec was founded in 1978 and is the world’s oldest independent biotechnology company. Its annual revenues top $5 billion.

For more information or to talk to a lawyer about a case of PML, please contact us today. Our attorneys represent patients with PML and their families across the country.

Source: http://www.medpagetoday.com/MeetingCoverage/AAN/37806

New Drug for Hodgkin Lymphoma Has Been Fatal for PML Patients

ADCETRIS™ (generic name: brentuximab vedotin) is a new drug for treating Hodgkin Lymphoma (HL). On March 26, 2012, the makers of ADCETRIS announced that their clinical trial of ADCETRIS was quite successful.

Three-quarters of the 100-plus HL patients treated with ADCETRIS showed lasting positive responses to the drug. However, the press release from Seattle Genetics, Inc., ADCETRIS’s developer and manufacturer, also notes that the latest Warnings and Precautions for ADCETRIS include the following:

“Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death [emphasis ours] has been reported in ADCETRIS-treated patients.

Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities.

Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.”

Moreover, the Boxed Warning for ADCETRIS states that ” Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.”

The results of this latest clinical trial, an open-label, phase II examination, have served as the basis for an accelerated FDA approval of ADCETRIS in August 2011. However, several patients who were treated with ADCETRIS have developed PML, which is a life-threatening complication. As is often the case with newly developed drugs, an accelerated approval is controversial, and the FDA has ended up later “revising” its approval for new drugs when complications and side effects accumulate.

In fact, in January 2012, after several new cases of PML in ADCETRIS-treated patients were reported, the FDA required that the ADCETRIS warnings be updated to warn of this risk.

ADCETRIS is also FDA-approved for the treatment of anaplastic large-cell lymphoma (ALCL). When a person with HL or ALCL is treated with ADCETRIS, he or she should be aware of the symptoms of PML, which include:

  • confusion
  • loss of cognition/ability to think clearly
  • physical weakness
  • sudden problems with vision, walking, or speech
  • unexplained changes in mood or behavior

If you have concerns related to ADCETRIS or another drug related to PML, talk with a knowledgeable PML lawyer by contacting us today.

Positive JCV Test Found As New Risk Factor for PML

Testing positive for anti-JC virus (JCV) antibodies is a newly identified risk factor for a rare, but serious brain disorder associated with the drug Tysabri® (natalizumab), according to a U.S. Food and Drug Administration (FDA) Safety Announcement.

Tysabri® is prescribed to treat multiple sclerosis or Crohn’s disease. Progressive multifocal leukoencephalopathy (PML) is a rare brain infection in which the coating of some brain nerve fibers called myelin is damaged. Tysabri® has been associated with increasing the risk of getting PML.

Two hundred and one patients with PML have been reported among about 96,582 patients given Tysabri® worldwide through Jan. 4, 2012. Patients who have taken Tysabri® for between 25 and 48 months number 11 in 1,000 if they have been treated previously with an immunosuppressant.

Doctors and patients are warned in the FDA announcement to carefully weigh the risks versus the benefits of continuing treatment with Tysabri® in patients who have:

  • JCV antibodies
  • Been treated longer with Tysabri®, especially longer than two years
  • Have had prior treatment with an immunosuppressant drug such as mitoxantrone, azathioprine, methotrexate, cyclophosphamide, or mycophenolate mofetil.

The risk of getting PML is greatest if you have all three known risk factors.

The new information has been added to the Tysabri® drug label. A new anti-JCV detection test was approved by the FDA on January 20, 1012.

Because of this new information, your doctor may recommend a blood test to see if you have ever been exposed to JCV, which is the virus that causes PML. This test measures the presence of antibodies to the virus. These antibodies often are called anti-JCV antibodies.

PML symptoms are varied and progress over a matter of days to weeks. They include

  • Progressive weakness on one side of the body
  • Clumsiness
  • Disturbed vision
  • Changes in thinking, memory and orientation, leading to confusion and personality changes

The progression of the disease can lead to death or severe disability over weeks or months.

For more information, contact a progressive multifocal leukoencephalopathy lawyer today.

New Antibody Test Shown to Indicate PML Risk

If you test positive for having antibodies to the JC virus (JCV), you have an increased risk of getting progressive multifocal leukoencephalopathy (PML), according to a Food and Drug Administration (FDA) Safety Communication released Jan. 20, 2012.

PML is a rare serious infection of the brain that occurs in patients treated with Tysabri® (natalizumab) for multiple sclerosis (MS) or Crohn’s disease.  Patients and their doctors should discuss the risks and benefits of taking Tysabri® for MS or Crohn’s disease.

There are three risk factors for PML. A patient having all three has of getting PML of 11 in 1,000. The three risk factors are:

  • The presence of anti-JCV antibodies
  • Long-time treatment with Tysabri®, in particular longer than two years
  • Prior treatment with an immunosuppressant medication

Patients should talk with their physicians if they develop symptoms that characterize PML. Symptoms vary and become worse over a period of days or weeks. These symptoms include progressive weakness on one side of the body, clumsiness, problems seeing, changes in thinking, memory and orientation that end in confusion and personality changes.

If you test positive for the presence of anti-JCV antibodies, you have been exposed to JCV in the past.

The drug label accompanying a Tysabri® prescription reflects this new information.

The nerve fibers of patients with PML have been damaged. It is a rare disease that does not harm people with normal-functioning immune systems. People with weakened immune systems are more susceptible to the disorder, in particular people who are immunodeficient due to having HIV infection (the human immunodeficiency virus); having leukemia or lymphoma; taking Tysabri®.

It still is possible to be at risk for developing PML, even if you test negative for anti-JCV antibodies. This is because it is possible to get a new JCV infection or for test results to be inaccurate.

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For more information, contact a PML lawyer today.

FDA Clears Phase II Trial of Drug to Treat JC Virus

The pharmaceutical company Inhibikase Therapeutics has received a green light from the U.S. Food and Drug Administration (FDA) to conduct a phase II clinical trial on a drug to treat the JC virus. The authorization to do the study is significant because the JC virus causes a deadly brain disease that occurs in patients with compromised immune systems.

The trial is called a “proof of concept” trial.  “Proof of concept” trials are done in the early stages of human drug testing to see if the basic reason for the drug’s working and doing so safely can be substantiated.

The JC virus is a dormant virus living in between 80 to 90 percent of adults.  It remains harmless unless it is triggered by some assault on the patient’s immune system.  When this happens, the virus is activated, travels through the bloodstream to the brain, and begins to destroy brain cells. The disease it unleashes is called progressive multifocal leukoencephalopathy (PML).

PML kills most of its victims within 1 to 9 months. The average lifespan after diagnosis is 6 months.  Those who survive are left with significant neurological deficits.

The JC virus is activated, leading to PML, in patients with AIDS, HIV, and others with compromised immune systems, including people on chemotherapy for cancer, and patients receiving immunosuppressive drugs for organ transplants, rheumatoid arthritis, system lupus erythematosus, Crohn’s disease, severe plaque psoriasis, and multiple sclerosis.

The drug being tested is called Ik T-001.  If it succeeds in combatting the JC virus before the virus is activated and sets off PML, the drug would be a life saver for many patients with comprised immune systems and those on drugs to treat autoimmune diseases (diseases in which the immune system attacks the body).

Inhibikase Therapeutics was founded in 2008.  It is developing early-stage drugs to treat viral and bacterial diseases and opening new avenues for vaccine development and biodefense.

Elan Profits Nearly Triple Thanks to MS Drug Sales

Second-quarter profits for the Irish drug company Elan came close to tripling due to hefty sales of Tysabri®, its drug to treat multiple sclerosis.

Elan co-markets the drug with Biogen.  Biogen issued higher than expected quarterly figures for Tysabri® in July, indicating the number of new users increased at the highest rate in over a year.

“We are making progress across all aspects of our company,” said Chief Executive Kelly Martin.

“Tysabri® continues to grow in double-digits,” he said. “Demand for the product is strong both in the U.S. and outside the U.S.”

The company makes an added $100 million every time 10,000 more patients buy Tysabri®. It is expected that the medication will increase the overall growth in the company’s bottom line by 15 percent annually for the next three to five years.

Tysabri® (the generic is natalizumab) is a monoclonal antibody. It was approved in November 2004, but pulled from the market several months later when a few patients taking the medication to treat multiple sclerosis contracted a fatal brain infection, progressive multifocal leukoencephalopathy (PML).

PML is a lethal viral disease of the brain. The virus, known as the JC virus, remains latent in the human body until it overcomes a weakened immune system.  Once in the brain, it begins to destroy the myelin covering of the nerve cells.  Progressing in an inexorable downward spiral, PML kills most victims within an average of six months.

Tysabri® was released back onto the market in June 2006 with onerous restrictions on who could use the drug.  Patients had to be enrolled in and were monitored by a strict “risk mitigation strategy” to keep track of any possible symptoms of PML in Tysabri® patients. The strategy helped physicians know more about and manage the risks of PML in their patients.

One In 25,000 Patients Treated with Rituxan Risk PML

An arthritis patient on the medication Rituxan™ faces a one in 25,000 chance of getting the deadly brain disease progressive multifocal leukoencephalopathy (PML), according to researchers at Washington University in St. Louis.

David B. Clifford, M.D. and his co-workers published their report in an online issue of Archives of Neurology. The group found four cases of PML in approximately 129,000 patients taking Rituxan™ (the generic is rituximab) for rheumatoid arthritis.

Among the four, two patients died within a year of diagnosis of PML. Of the two remaining patients, whose Rituxan™ treatment was stopped, one had no further symptoms of PML and the other, although cognitively impaired, has regained her ability to walk.

The researchers urged physicians treating patients with Rituxan™ to think twice about prescribing the drug because of the lethality of PML. In those patients who are treated with the medication, doctors should know that "aggressive evaluation of new and progressing neurological deficits is very important to allow early diagnosis. No further rituximab should be used if a suspicious neurological symptom or sign appears until the diagnosis is successfully excluded," the authors urged.

PML is a disease of the brain, caused by the J.C. virus. The virus exists in 80 to 90 percent of adults and remains latent until the immune system is weakened. The opportunistic infection then travels through the blood stream to the brain, where it inexorably progresses to destroy the myelin.  Myelin is a substance that covers the nerves, protecting them and enabling them to transmit signals faster to the rest of the body.

With the destruction of the nerves, patients with PML experience unrelenting diminishment of their capacities.  The first sign of the disease is usually clumsiness.  Progressing slowly at first, the disease continues to destroy brain tissue and with it the concomitant function of the body parts and organs that are affected.

The disease attacks patients with HIV and AIDS and others with immune system deficiencies, caused either by disease or by drugs used to treat disease. Victims include patients on chemotherapy for cancer and patients receiving immunosuppressive drugs for organ transplants, rheumatoid arthritis, systemic lupus erythematosus, Crohn’s disease, severe plaque psoriasis, and multiple sclerosis.

If you’ve been diagnosed with PML and have been treated with Rituxan™, you might be eligible for compensation. Contact our PML attorneys to schedule a free case review.

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