Tecfidera Linked to PML Once Again

A second case of progressive multifocal leukoencephalopathy (PML) has been reported in an MS patient taking Tecfidera (delayed-release dimethyl fumarate), an oral disease-modifying therapy approved to treat relapsing forms of multiple sclerosis.

Biogen reported the case to the Food and Drug Administration (FDA); however, details of the report are not available on the Drugs@FDA website nor on Biogen’s company website.

This case will not likely require any change to the prescription label. The FDA had already updated the Tecfidera label in December 2014 to warn of the risk of PML, following the death of a 54-year old woman with MS who had participated in the DEFINE clinical trial and experienced severe lymphopenia for 3.5 years.

Reports of the earlier case of PML, as well as another fatal case in a patient using a compounded version of dimethyl fumarate for the treatment of psoriasis, were published in an April edition of The New England Journal of Medicine. Surprisingly, the patient with psoriasis who died in August 2014 did not have two of the known risk factors for PML: severe lymphopenia and exposure to immunosuppressive therapy.

Biogen spokesperson Catherine Falcetti told MedPageToday that this most recent case of Tecfidera-related PML involved a patient diagnosed with primary progressive MS who had prolonged severe lymphopenia. Decreased lymphocyte counts (i.e., lymphopenia) is a known side effect of dimethyl fumarate, indicating a lowered immune system.

PML is a rare and serious brain infection caused by the John Cunningham (JC) virus. The JC virus is a common virus that is harmless in most people but can cause PML in some patients who have weakened immune systems. PML can lead to death or severe disability. In this case, the patient didn’t die, but Biogen has not reported the patient’s condition nor where this case occurred.

Tecidera was approved in the US for the treatment of relapsing forms of MS in March 2013, and, since that time, has been used by more than 135,000 people worldwide. Tecfidera quickly gained popularity within the competitive MS disease-modifying therapy market following its launch, however sales began to slow in the first quarter this year.

Biogen will announce results from the second quarter earnings next Friday on July 24, 2015. It is possible that more information regarding this most recent case of Tecfidera-related PML may be shared during the conference call.

In April 2015, Biogen initiated a Phase 3 study of Tecfidera in secondary progressive multiple sclerosis.

At the time of FDA approval, there were no known cases of PML, or other opportunistic infection, in patients taking Tecfidera for MS; however, PML had previously been reported in Europe in patients treated with other drugs containing dimethyl fumarate. Three of those cases occurred in patients with psoriasis who took Fumaderm and one case in a patient treated with a compounded product that included dimethyl fumarate. Two of these patients had prolonged lymphopenia and two had previous exposure to immunosuppressive therapy.

Doctors should remain vigilant about monitoring lymphocyte counts in Tecfidera-treated patients, and stop treatment immediately at the first sign or symptom suggestive of PML.

Patients should contact their doctor if they develop any symptoms suggestive of PML. Symptoms of PML are diverse and may include progressive weakness on one side of the body, clumsiness, vision problems, confusion, and changes in thinking, personality, memory, and orientation. The progression of deficits can lead to severe disability or death.1-5

Do not stop taking prescribed medications without first talking to your doctor.

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