What Is Progressive Multifocal Leukoencephalopathy (PML), What Causes It, Why Is Tysabri Still On The Market?
(Posted by Tom Lamb at DrugInjuryWatch.com)
On April 17, 2009 we learned that another multiple-sclerosis patient using the multiple-sclerosis (MS) drug Tysabri developed progressive multifocal leukoencephalopathy, or PML, a rare brain infection. This is the sixth MS patient who has been diagnosed with PML since Tysabri was reintroduced on the market in July 2006.
We get some insightful additional information from a Dow Jones article, "Biogen Says Sixth MS Patient On Tysabri Gets Brain Infection":
Tysabri - sold by the Cambridge, Mass., biotech [Biogen Idec Inc. (BIIB)] with Ireland-based partner Elan Corp. PLC (ELN) - was pulled from the market for 18 months beginning in 2005 because of a suspected link to the rare brain infection. Before Friday, the company had reported five confirmed cases, with one death, since the relaunch.
The latest case was outside the U.S., as were four of the previous five. Biogen didn't disclose additional details on the patient's condition.
Biogen plans to post a case update every Friday until July 24, the third anniversary of relaunch, by which time it expects the risk/benefit profile to be clearer.
The PML rate implied on Tysabri's label is one-per-1,000 patients. As of the end of March, about 40,000 patients were using Tysabri and about 24,900 patients have received at least one year of therapy. Chief Executive Jim Mullen, before Friday, had stressed the current rate for patients taking the drug more than 12 months is about one-per-4,000.
Some believe that duration of therapy plays a role in Tysabri's PML risk. The company said Thursday that about 6,800 patients have used the drug for more than two years, which is a rise of 2,500 from three months ago.
Earlier this month, on April 9, the biotech company Genentech announced that it was withdrawing its psoriasis medicine Raptiva from the market because it can cause PML. This Raptiva recall came after just four cases of PML had been reported in patients taking Raptiva, all of whom had reportedly been on Raptiva for at least three years.
The recent recall of Raptiva has some people asking this question: Why is Tysabri still on the market?
A good discussion of that question -- as well as an explanation of the PML disease process -- can be found in an April 20, 2009 Los Angeles Times article, "Psoriasis, Raptiva and PML: Why Genentech pulled the drug". In relevant part:
Tysabri was pulled from the market in 2005 after three patients taking it for their multiple sclerosis developed PML. This was a big blow, because clinical trials had demonstrated the drug cut MS relapse rates -- bouts of worsening neurologic function -- by more than half. In June 2006, the Food and Drug Administration approved Tysabri's return to the market with a carefully crafted set of safety checks. Patients see their physicians monthly to be checked for features suggestive of PML -- basically, "anything new that can't be explained by the multiple sclerosis," Berger says. These include neurological symptoms, loss of white matter (which can be detected with MRI) and the presence of JC virus in spinal fluid.
Dr. Melvin Chiu, a dermatologist at the UCLA David Geffen School of Medicine who directs UCLA's Psoriasis and Phototherapy Center, says the situation with Tysabri differs from Raptiva when you consider the severity of the disease each drug is meant to treat. "That's not to say psoriasis is not disabling, but it doesn't have the life-threatening connotations that multiple sclerosis has," he says. "So from a risk-benefit analysis, it might not be worth the risk to be on Raptiva, especially given that there are several other therapies available for psoriasis patients that don't carry that risk."
We will watch for any additional reports of the brain infection PML in patients using Tysabri from Biogen -- which, as stated above, will be providing weekly reports at least until July 24, 2009 -- or from other sources.