Daclizumab

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Daclizumab
Mass / length primary structure 142.6  kDa
Identifier
External IDs
Drug information
ATC code L04 AA08
DrugBank BTD00007
Drug class Immunosuppressant

Daclizumab is a therapeutic humanized monoclonal antibody against the interleukin-2 receptor (more precisely: against the CD25 α chain ) that was originally used in the immunosuppressive treatment of acute rejection reactions after kidney transplants . In 2016, the daclizumab preparation Zinbryta was approved for the treatment of relapsing multiple sclerosis in the EU and the USA. In March 2018, the active ingredient was withdrawn from the market worldwide due to serious adverse effects. At the same time, the European Medicines Agency (EMA) issued a corresponding recommendation . In May 2018, the EMA revoked the approval and Zinbryta was recalled from hospitals and pharmacies.

properties

Daclizumab is a humanized monoclonal antibody of the IgG 1 type . The antibody is produced recombinantly in cell cultures of murine GS-NSO myeloma cells .

Adverse effects (side effects)

In June 2017, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) started a procedure to investigate the death of a patient treated with daclizumab due to liver failure. There are also four cases of severe liver impairment. During this investigation, use of daclizumab will be limited to patients with highly active, relapsing disease who are not responding to other treatments, as well as those with rapidly developing relapsing disease who cannot be treated with other drugs. In addition, the drug must not be given to patients with liver damage. In October 2017, the PRAC recommended that daclizumab be subject to further restrictions. To reduce the risk, doctors should only prescribe the drug for recurrent forms of multiple sclerosis, and only if patients have not responded adequately to at least 2 other disease-modifying therapies and cannot be treated with other disease-modifying drugs. The patient's liver function (ALT, AST, bilirubin) should be checked at least once a month before treatment with daclizumab. Liver function should be monitored for 6 months after treatment is stopped. Daclizumab should not be used in patients with pre-existing liver disease and in patients with liver enzyme levels above 2 times the upper limit of normal. The PRAC also advises against its use in multiple sclerosis patients who have other autoimmune diseases.

In March 2018, the active ingredient was withdrawn from the market due to severe adverse effects ( encephalitis , meningoencephalitis ), some of which were fatal. In May 2018, the EMA revoked the approval.


history

Daclizumab was developed by the American biotechnology company PDL Biopharma at the National Institutes of Health based on the research results of Thomas Waldmann's group . The first registration took place in December 1997 in the USA; Daclizumab was the first humanized antibody to be approved by the FDA. Approval for the European Union was granted in February 1999. In 2006 Hoffmann-La Roche applied to the EU Commission to withdraw the approval of Zenapax for commercial reasons; the decision is said not to have been related to concerns about the safety of the drug. In June 2008 the EU Commission made a corresponding decision with effect from January 1, 2009.

PDL Biopharma formed an alliance with the biotechnology company Biogen Idec to develop daclizumab for the treatment of multiple sclerosis . When it was re-approved in 2016 under Zinbryta , the drug was dubbed the “miracle weapon of neurologists” in specialist journals. Zinbryta won the Neurologist's Most Innovative Product award in 2017. Thousands of MS patients in Germany were quickly switched to the new drug, which was expected to slow the progression of the chronic nerve disease. The EMA had approved it without restrictions, so that it was also prescribed to patients with milder disease, while the American FDA had only permitted its use to a limited extent. The EMA justified itself by stating that the benefits of Zinbryta outweighed the risks - a misjudgment because at least seven people died due to the most severe side effects and more are said to be in intensive care units all over Germany. German patients were primarily affected, of whom more than 2,890 patients were switched in the first year after readmission (in the rest of Europe there were only 400). Biogen is said to have spread premature optimism in marketing; serious side effects and even deaths are said to have occurred in the approval studies that the manufacturer did not bring in connection with the drug.

In March 2018, the active ingredient was withdrawn from the market due to the serious adverse effects (encephalitis, meningoencephalitis), some of which were fatal.

Trade names

  • Zenapax (withdrawn from the market in 2009)
  • Zinbryta (withdrawn from the market in 2018)

See also

Individual evidence

  1. ↑ European public assessment report on Zinbryta ema.europa.eu
  2. ↑ FDA approval documents for Zinbryta accessdata.fda.gov .
  3. ↑ a b c Biogen and AbbVie announce the independent global withdrawal of the marketing authorization of Zinbryta (daclizumab) for the treatment of multiple sclerosis , PM Biogen of March 2, 2018, accessed on March 15, 2018
  4. ↑ a b c Voluntary withdrawal of ZINBRYTA® (daclizumab) in United States , Prescriber Letter from Biogen dated March 12, 2018, accessed on March 15, 2018.
  5. ↑ a b c EMA recommends immediate suspension and recall of multiple sclerosis medicine Zinbryta , PM EMA of March 7, 2018, accessed on March 15, 2018.
  6. ↑ a b EMA review of Zinbryta confirms medicine's risks outweigh its benefits , PM EMA of May 18, 2018, accessed on May 19, 2018.
  7. ↑ EMA review s multiple sclerosis medicine Zinbryta , PM EMA, June 9, 2017, accessed June 9, 2017
  8. ↑ PRAC Launches Safety Review of MS Drug Daclizumab (Zinbryta) , Medscape.com, June 9, 2017, accessed June 9, 2017.
  9. ↑ EMA restricts use of multiple sclerosis medicine Zinbryta , PM EMA of July 7, 2017, accessed July 12, 2017.
  10. ↑ Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) October 23-26, 2017 , PM EMA of October 27, 2017, accessed on October 27, 2017.
  11. ^ TA Waldmann: Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey. In: J Clin Immunol. 27 (1), Jan 2007, pp. 1-18. PMID 17216565 .
  12. ↑ N. Tsurushita, PR Hinton, S. Kumar: Design of humanized antibodies: from anti-Tac to Zenapax. In: Methods. 36 (1), May 2005, pp. 69-83. PMID 15848076 .
  13. ↑ EMEA public statement on the market withdrawal of daclizumab (Zenapax presentation of the approval history of daclizumab on the website pharmacologycorner.com, January 2009, accessed on March 15, 2009.
  14. ↑ Zinbryta is “The Most Innovative Product” 2017 by the neurologists pharma-trend.com from September 12, 2017
  15. ↑ plusminus of February 20, 2019

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