Biogen issues alert after 2 Rituxan deaths

Biogen Idec Inc. said yesterday that two patients using its drug Rituxan have died of a rare brain infection, the same one that shadows its multiple sclerosis treatment Tysabri .

In a letter sent to doctors, Biogen and Genentech Inc., which co-markets Rituxan with the Cambridge drug maker, warned that the two patients had contracted fatal progressive multifocal leukoencephalopathy, or PML.

Both patients were being treated for lupus, a disease in which Rituxan use is still considered experimental.

The drug is approved only for use in rheumatoid arthritis and non-Hodgkin's lymphoma , a form of blood cancer, but doctors are allowed to prescribe it for other diseases at their discretion.

In a posting on its website, the Food and Drug Administration said it was looking into the deaths.

The "FDA is working to gather more information about Rituxan and PML and to strengthen the warnings about PML in the Rituxan product label," the agency said.

The FDA warned doctors who prescribe Rituxan to be on the lookout for PML symptoms, which include dizziness, difficulty talking, and vision problems.

The disease, a viral brain infection that is usually fatal, strikes patients with compromised immune systems.

Last year, Biogen Idec withdrew Tysabri from the market shortly after its introduction, after three cases of PML were reported and two of the patients died. After a Food and Drug Administration hearing, the company brought Tysabri back to the market earlier this year.

Rituxan is one of the biggest-selling biotechnology drugs in the world, generating $1.8 billion in sales in 2005.

Biogen Idec recorded $709 million of that revenue, making Rituxan its second-biggest seller, after the multiple sclerosis treatment Avonex. Rituxan was discovered by Biogen Idec.

In a "Dear Healthcare Provider" letter posted yesterday on Genentech's website, the companies also said 23 cases of PML had been reported in blood-cancer patients taking Rituxan. The label for Rituxan already includes a warning about PML in those cases.

"This is the first time we've seen it outside the oncology setting," said Biogen Idec spokesman Tim Hunt. "We want to alert the prescribing public that it's been observed."

Both Rituxan and Tysabri are antibodies, a complex molecule modeled on a component of the human immune system.

Hunt said Biogen Idec didn't believe there was a link between the PML cases in Tysabri and Rituxan patients.

"I think the reality is, you see PML with a lot of patient populations," he said.

Hunt said PML is also seen in cancer and lupus patients not undergoing Rituxan treatment.

Rituxan is currently in clinical testing on patients with lupus, multiple sclerosis, and cancer. In addition to revising the label, the makers will obtain renewed consent forms from patients currently in Rituxan clinical trials. The patients who died were not in a clinical trial.

Stephen Heuser can be reached at sheuser@globe.com.