The European Medicines Agency has restricted the use of Zinbryta (daclizumab) for relapsing multiple sclerosis after reports of patients experiencing severe liver damage and one dying of liver disease.
The temporary order restricts Zinbryta to European Union patients with a highly active disease who have failed to respond to other disease-modifying therapies, and patients with a rapidly evolving disease who cannot be treated with other disease-modifying drugs.
The U.S. Federal Drug Administration, which like European regulators is aware that Zinbryta can be toxic to the liver, has yet to restrict its use.
Patients with liver damage should not take Zinbryta under any circumstances. The same applies to those with another autoimmune disease in addition to MS.
The agency’s Pharmacovigilance Risk Assessment Committee asked for the restrictions after learning about the death of a patient enrolled in an ongoing observational study of Zinbryta. The patient died of liver failure. Four patients developed severe liver damage.
The liver injuries occurred at different times in the treatment course. The range was from early in the treatment to several months after a patient stopped taking the medication.
The risk assessment committee said its recommendation was aimed at ensuring that Zinbryta is used in the safest way possible while researchers review its safety. When the review is finished, both patients and doctors will receive more information, it added.
Doctors should make a prompt check of whether patients on Zinbryta should continue taking it or switch to another drug. Physicians should perform monthly liver checks on those who continue. If they detect any sign of liver injury, they should refer their patient to a liver specialist.
Meanwhile, patients should learn to recognize the symptoms of liver injury: unexplained nausea, vomiting, abdominal pain, fatigue, loss of appetite, yellowing of the skin and eyes, and dark-colored urine. Patients should contact their doctor immediately if they experience any of these symptoms while on Zinbryta.
Although it’s understandable that patients may be concerned about Zinbryta’s safety, the medicines agency advises against stopping the medicine without first consulting a physician.
Patients should also tell their physicians about other medications they are taking, including herbal medicines and supplements. This is because Zinbryta’s impact on the liver can become worse when it is combined with certain compounds.
European regulators were aware of the possibility that Zinbryta could cause liver damage when they approved it in July 2016 on the recommendation of the medicine agency’s Committee for Medicinal Products for Human Use.
The approval declaration specified that doctors needed to monitor patients for liver damage, and that Biogen should inform doctors and patients about the risks. The new restriction indicates that this precaution was insufficient.
The European Commission, which gives final approval to new drugs marketed in the European Union, requested the new review of Zinbryta, which the Pharmacovigilance Risk Assessment Committee will carry out. Once the review is concluded, the committee will forward its findings to the Committee for Medicinal Products for Human use, which will issue a recommendation to the European Commission. The commission will then make a decision on Zinbryta’s future.
Zinbryta received Food and Drug Administration approval in May 2016. It is available through a restricted distribution program under an FDA Risk Evaluation and Mitigation Strategy. It also carries a label warning of potential liver toxicity.
The FDA has yet to change its Zinbryta prescribing information or its recommendations on how it should be used.