Another case of PML for Tysabri

[ActiveMSers]

UPDATE #3: For clarification, PML now reported technically in 13 cases. Story in the Wall Street Journal June 30.
http://online.wsj.com/article/SB124631389418370485.html

UPDATE #2: The PML risk is rising due to the 10th case. Scroll down to post #8.

UPDATE #1: Scroll down to post #6 to some great news about Tysabri. The risk of PML is much lower than originally thought. - Dave


Biogen reports brain infection in one more multiple sclerosis patient
10/30/2008 12:1 AM ET

Drug developer Biogen Idec Inc. (BIIB) Wednesday reported in a regulatory filing that a multiple sclerosis patient who was being treated with the company's Tysabri in the commercial setting in the U.S. developed progressive multifocal leukoencephalopathy or PML.

According to the Cambridge, Massachusetts-based company, the diagnosis was made after a JC Virus DNA was detected in the cerebrospinal fluid in the setting of clinical signs, symptoms and magnetic resonance imaging findings consistent with the diagnosis of PML.

The company noted that the patient has a history of multiple sclerosis and prior disease modifying therapies, including beta-interferons and glatiramer acetate. The patient had also received prior therapy with methotrexate for a rheumatological condition and received 14 infusions of Tysabri monotherapy.

Biogen said clinical vigilance led to early identification of signs and symptoms of possible PML and to clinical evaluation that included MRI scanning and CSF testing. The patient is under the care of the treating physician.

Tysabri, marketed by Elan Corp Plc. (ELN), was withdrawn from the market in 2005 after three patients developed brain infection. The drug re-emerged in 2006 with warnings after the FDA decided that MS patients ready to face the risks of the drug should have access to its benefits. The latest is the third case reported since July.

Last month Biogen and Elan said a post-hoc analysis of Tysabri, when compared to placebo over two years, showed sustained improvements in its functional outcome, rather then merely slowing or preventing progression of the disability.

[Angel@]

never cool to read this. here in the Netherlands there are quite a lot of people who take/use tysabri..

hope everybody is fine.

[KristaH]

I wince to think that the side effects are worse than what they are trying to help!

[beckyb]

maybe my doc is right

It surprises me that this patient was allowed to go on Tysabri after Methotrexate. That's what I am on currently (under the brand name Novantrone) and the down side is that is modifies the immune system - really limiting me going on Tysabri or some of the other promising meds coming up.

[beckyb]

maybe my doc is right

It surprises me that this patient was allowed to go on Tysabri after Methotrexate. That's what I am on currently (under the brand name Novantrone) and the down side is that is modifies the immune system - really limiting me from going on Tysabri or some of the other promising meds coming up.

[ActiveMSers]

Better news just out today! - Dave

Incidence Of PML With Tysabri In Multiple Sclerosis Lower Than Previously Thought
08 May 2009

The risk of developing progressive multifocal leukoencephalopathy (PML), a viral brain infection, in patients with multiple sclerosis (MS) taking the drug natalizumab (Tysabri) appears to be much lower - and the infection less deadly - than previously estimated, according to new postmarketing surveillance data.

Previous research found that the risk of developing PML was 1 in 1000, but new data show that the risk is closer to 1.2 per 10,000 patients, according to Carmen Bozic, MD, vice president and global head of drug safety and risk management for the maker of natalizumab, Biogen Idec, in Cambridge, Massachusetts.

Dr. Bozic delivered an updated overview of the risks and benefits of natalizumab during the American Academy of Neurology (AAN) 61st Annual Meeting.

Approved In 40 Countries

Natalizumab is approved in over 40 countries for the treatment of relapsing forms of MS to reduce the frequency of relapses and delay worsening of physical disability in patients who have had an inadequate response to or are unable to tolerate another MS medication. The drug is approved in the United States, Canada, Europe, Australia, and parts of the Middle East and Latin America. It is also approved in the United States to induce and maintain clinical response and remission in adult patients with moderately to severely active Crohn's disease.

Natalizumab is an antibody rather than an interferon; Biogen Idec also manufactures an interferon beta1-a drug (Avonex) for newly diagnosed MS patients. It works by preventing white blood cells from entering the brain and attacking nerves.

The data presented were taken from the Tysabri Outreach: Unified Commitment to Health (TOUCH) prescribing program and the Tysabri Global Observation Program in Safety (TYGRIS), both part of a global risk-management program to further evaluate the safety of natalizumab. TOUCH is a mandatory prescribing program for all patients, physicians, and infusion centers in the United States that ensures "appropriate and informed use of natalizumab," the researchers note. TYGRIS is a global voluntary observational study evaluating the long-term safety of natalizumab in clinical practice. Data from countries that do not participate in either TOUCH or TYGRIS were also collected.

As of the end of March 2009, or about 3 years after approval in the United States and the European Union, approximately 52,000 patients had been treated with natalizumab in the postmarketing setting. "This is more than 10 times the exposure we had in clinical trials," said Dr. Bozic.

Long-Term Exposure

As well, there is now much more information on the drug's long-term exposure in the postmarketing setting, she said. To date, about 24,900 patients have been taking the drug for 12 months or longer, 14,400 for 18 months or longer, and 6800 for 24 months or longer. Some patients have taken the drug for more than 2.5 years, she added.

"So both overall exposure and long-term exposure is significantly greater than we had in the original clinical trials, and that gives us a very robust ability to evaluate the safety of the drug," she told Medscape Neurology & Neurosurgery.

Of the 52,000 patients who have taken the drug, there have been 6 cases of PML, or an incidence of approximately 1.2 per 10,000 patients treated. "It's trending lower than what we saw in the clinical-trial setting," said Dr. Bozic.

The 6 patients - 3 men and 3 women aged 37 to 59 years - had taken the drug as monotherapy for periods ranging from 12 to 31 months. "This is a highly variable duration of treatment," noted Dr. Bozic.

Helen Yates, Chief Executive of the Multiple Sclerosis Resource Centre said, "It is obviously good news to see that the incidence of PML looks much lower than was first supposed. We would still like to see more investigation into the potential causal links between Tysabri and PML and of course the potential to develop this life-threatening condition does still remain"

Source
American Academy of Neurology

Article URL: http://www.medicalnewstoday.com/articles/149354.php

Main News Category: Multiple Sclerosis

Also Appears In: Neurology / Neuroscience,

[cochrajk]

I don't use Tysabri, but my hubby and I just went to a three hour seminar put on by Biogen. The neurologist speaking was talking about a possibility of a link between PML and low CD4 counts...under 200 or something like that. He stated that he and other neuros at Georgetown take patients off Tysabri if their CD4 counts are 500 or less and they check labs every three months.

I think that the risk is less, but it sounds like neuros are also trying to help lower the risk with what they think might be causal relationships too.

[ActiveMSers]

A 10th case of PML in Tysabri was just announced, which makes three in the last month. All had taken the drug for more than 30 months. Ugh. Let's hope long-term use does not increase the risk of the nasty brain disease.