Biogen Idec First Added Information About Tecfidera Being Assoicated With PML Brain Infection Back In December 2014, After An FDA Drug Safety Communication Was Issued
Tecfidera is a drug used to treat relapsing forms of multiple sclerosis (MS).
There is a February 29, 2016 FDA letter to Biogen Idec about a revision to the prescribing information for Tecfidera (dimethyl fumarate) having to do with progressive multifocal leukoencephalopathy (PML).
But that FDA letter does not inform one further about the new drug safety information for Tecfidera concerning progressive multifocal leukoencephalopathy (PML). To see what is new, one must read Section 5.2 of the current version of the Tecfidera label (Revised: 2/2016), where an added paragraph suggests two developments. The first is that there seems to have been more Tecfidera - PML cases reported in the past year or so. And the second is that lymphonpenia possibly induced by Tecfidera might have a role to play in those additional PML cases. Here is the added paragraph, short but significant, it seems:
[Progressive multifocal leukoencephalopathy (PML)] has also occurred in the postmarketing setting in the presence of lymphopenia (<0.8x109/L) persisting for more than 6 months. While the role of lymphopenia in these cases is uncertain, the majority of cases occurred in patients with lymphocyte counts <0.5x 109/L.
We start with the apparent increase in the number of Tecfidera - PML cases that have been reported to Biogen Idec and/or the FDA.
This February 2016 Tecfidera label change about PML can be compared to December 2014 FDA-approved version of the Tecfidera drug label, when information about the apparent PML side effect was first added. And that earlier Tecfidera label change seems to have been based on this document, "FDA Drug Safety Communication: FDA warns about case of rare brain infection PML with MS drug Tecfidera (dimethyl fumarate)", issued November 25, 2014, as indicated by this excerpt:
The U.S. Food and Drug Administration (FDA) is warning that a patient with multiple sclerosis (MS) who was being treated with Tecfidera (dimethyl fumarate), developed a rare and serious brain infection called PML, and later died. As a result, information describing this case of PML, or progressive multifocal leukoencephalopathy, is being added to the Tecfidera drug label. Patients taking Tecfidera should contact their health care professionals right away if they experience symptoms that concern them, such as new or worsening weakness; trouble using their arms or legs; or changes to thinking, eyesight, strength or balance. Health care professionals should stop Tecfidera if PML is suspected....
The patient who died was not taking any other drugs that affect the immune system or drugs that are thought to be associated with PML. This is the only confirmed case of this rare and serious brain infection reported in patients taking Tecfidera. [emphasis added]
Now it appears there have been more cases of progressive multifocal leukoencephalopathy (PML) in the postmarketing setting, i.e., since Tecfidera was approved by the FDA in 2013.
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Next, we move to the suspected involvement of lymphopenia (i.e., reduction in the number of lymphocytes circulating in the blood) with the apparent additional Tecfidera - PML cases.
To start, we return to the November 2014 FDA Drug Safety Communication about Tecfidera:
The drug manufacturer, Biogen Idec, notified FDA when the MS patient died after developing PML. The patient had taken Tecfidera for more than four years. Prior to developing PML, the patient had a very low number of lymphocytes, a type of white blood cell, in her blood. Reduced lymphocyte counts can weaken the immune system, which increases the risk for PML. It is unknown whether the low lymphocyte count contributed to the development of PML in this patient, or if low lymphocyte counts are a risk factor for PML development in Tecfidera-treated patients.
But now, in that new paragraph found at "5.2 Progressive Multifocal Leukoencephalopathy" of the current Tecfidera label (Revised: 2/2016), there is this statement: "While the role of lymphopenia in these cases is uncertain, the majority of cases occurred in patients with lymphocyte counts <0.5x 109/L."
We will continue to monitor the safety profile of the MS drug Tecfidera, especially as regards case reports of progressive multifocal leukoencephalopathy (PML).
UPDATE: For some supplemental information on the matter, see this May 13, 2016 article, "Additional Cases of PML Found Among Those Taking Tecfidera", from our Drug Safety Developments site. (5/13/16)