Zinbryta (Daclizumab) for Multiple Sclerosis

Zinbryta (daclizumab), a humanized monoclonal antibody produced by Biogen and AbbVie, is an approved treatment for relapsing multiple sclerosis (RMS) in the U.S. and in Europe.

How Zinbryta works

Zinbryta is a formulation of a monoclonal antibody against the CD25 subunit of interleukin 2 (IL-2) receptors. These receptors are highly expressed on reactive T-cells in MS patients. By selectively targeting the T-cells with CD25, Zinbryta prevents the expansion of CD25-positive, autoreactive T-cells. It further promotes the activity of CD 65-positive natural killer cells, which clean up the already activated CD25-positive T-cells. Therefore, Zinbryta both stops and prevents inflammation caused by CD25-positive T-cells.

In the high-yield formulation, Zinbryta is intended to be administered subcutaneously (beneath the skin) once every four weeks. At this dose, Zinbryta binds to all CD25 receptors within 10 hours and remains bound for 64 days.

History of Zinbryta

Daclizumab was originally pursued for the treatment of acute organ rejection in patients with kidney transplants by Roche under the trade name Zenapax. The medication was available in the U.S. and European Union, but it was withdrawn for commercial reasons. Daclizumab is now called Zinbryta for use in RMS patients. Two clinical trials, DECIDE (NCT01064401) and SELECT (NCT00390221), formed the basis of the biological licence application (BLA) submission to the U.S. Food and Drug Administration (FDA) by Biogen and AbbVie.

The SELECT study compared the effect of different doses of daclizumab (300 mg and 150 mg) to placebo over a one-year period in participants with RMS and showed that the lower dose of daclizumab (150 mg) reduced the relapse rate by 54% compared to placebo.

DECIDE, a Phase 3 study involving 1,841 participants with RMS, showed that Zinbryta reduced the rate of relapses by 45% and also decreased the activity of the disease, as observed in MRI scans, over 144 weeks compared to Avonex, another drug approved for the treatment of RMS.

Next steps for Zinbryta

The FDA accepted Biogen and Abbvie’s BLA for Zinbryta for RMS, and Zimbryta was officially approved by the FDA on May 27, 2016.

The European Medicines Agency (EMA) also validated the Marketing Authorization Application for Zinbryta for the treatment of RMS, and a review process by EMA’s Committee for Medicinal Products for Human Use (CHMP) began in March 2015. About a year later, in April 2016, CHMP adopted a positive opinion, recommending marketing authorization in Europe for  Zinbryta to treat RMS.

The EMA eventually approved Zinbryta for the treatment of adult patients with RMS in July 2016.

The decision was followed by the National Health Service (NHS) in England and Wales in March 2017 and by the Scottish Medicines Consortium (SMC) on April 10, 2017.

In England and Wales, Zinbryta is indicated for the treatment of RMS in patients who have relapses while taking one of the other available disease modifying drugs, and for the treatment of rapidly evolving RMS when there were two or more relapses in the previous year as measured with magnetic resonance imaging (MRI).

In Scotland, Zinbryta can be prescribed for rapidly evolving severe RMS, or RMS with inadequate response to disease modifying therapy.

The benefits of Zinbryta in patients with secondary progressive MS (SPMS) have also been investigated, by PDL BioPharma, in 2008. Eight percent of the patients enrolled in a Phase 2 clinical trial (NCT00109161) had SPMS (the other 92% had RMS).

Other Zinbryta info

Zinbryta has a black box warning about the potential for severe liver injury, including life-threatening and fatal events. Therefore it is highly recommended that liver function is monitored before starting and during treatment with Zinbryta. Common side effects include skin rash and elevated liver enzymes.

Note: Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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Europe Restricts Use of MS Therapy Zinbryta After Liver Damage Cases and a Death

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.

In the meantime, the agency is taking a closer look at the Biogen drug’s safety profile, according to a press release.

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.

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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.

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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.

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