PRAC Further Restricts Daclizumab (Zinbryta) in MS

Megan Brooks


October 27, 2017

Because of the risk for liver damage, the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has recommended further restrictions on daclizumab (Zinbryta, Biogen/AbbVie), used to treat adults with relapsing forms of multiple sclerosis (MS).

A safety review by the committee found that "unpredictable and potentially fatal immune-mediated liver injury" can occur during treatment with daclizumab and for up to 6 months after discontinuation of the drug, the PRAC said today.

"In order to reduce the risks, doctors should now only prescribe Zinbryta for relapsing forms of multiple sclerosis in patients who have had an inadequate response to at least two disease modifying therapies (DMTs) and cannot be treated with other DMTs," the PRAC advised.

The committee launched a safety review of daclizumab back in June following the death from fulminant liver failure of a patient who was treated with daclizumab in an ongoing observational study, as well as the occurrence of four cases of serious liver injury.

One month later, amid their ongoing review, the PRAC issued provisional recommendations restricting use of the drug to patients who experience highly active relapsing MS despite having undergone a full and adequate course of treatment with at least one DMT or patients with rapidly evolving severe relapsing MS who are unsuitable for treatment with other DMTs. 

Today, the PRAC adopted final measures aimed to improve liver monitoring and limit use of daclizumab to patients who have had an inadequate response to at least two DMTs and cannot be treated with other such therapies.

Daclizumab, given as a once-monthly injection for adults with relapsing forms of MS, was first authorized for use in the European Union in July 2016.

Daclizumab was approved by the US Food and Drug Administration (FDA) for relapsing forms of MS in May 2016. The FDA cautioned, however, that daclizumab should be used only in patients who have not responded to one or two prior therapies because it carries serious safety risks, including potentially severe liver damage and immune conditions. In clinical trials, 1.7% of patients treated with daclizumab had a serious liver reaction.

Strict Liver Monitoring Required

The PRAC also advised today that clinicians monitor patients' liver function (alanine aminotransferase, aspartate aminotransferase, and bilirubin) at least once a month as closely as possible before each injection and continue monitoring patients for up to 6 months after injections have stopped. "If the patient does not comply with monitoring requirements or the response to treatment is inadequate, doctors should consider stopping treatment," the PRAC said.

The committee also recommends stopping daclizumab if a patient has liver enzyme levels over 3 times the normal limit and referring any patients with signs and symptoms of liver damage to a liver specialist. Patients who test positive for hepatitis B or C virus infection should also be referred to a specialist.

Daclizumab must not be used in patients with pre-existing liver disease and should not be started in patients with liver enzyme levels over 2 times the normal limit. The PRAC also advised against using daclizumab in patients with other autoimmune conditions.

In addition to the current educational material, the PRAC said patients and providers in the European Union should be given an acknowledgment form to confirm that providers have discussed the risks of daclizumab treatment with their patients and that the patients understand the importance of monitoring and checking for signs of liver damage.

These updated recommendations will be sent to EMA's Committee for Medicinal Products for Human Use, which will adopt a final opinion.

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