Daclizumab (Zinbryta), the anti-CD25 monoclonal antibody approved for the treatment of relapsing MS in May 2016 (December 2016 in Canada), has been voluntarily withdrawn by its manufacturers and will no longer be available. The withdrawal was announced on March 2, in a press release issued by Biogen and AbbVie (www.businesswire.com/news/home/20180302005168/en/Biogen%C2%A0and-AbbVie-Announce%C2%A0the-Voluntary%C2%A0Worldwide-Withdrawal-Marketing-Authorizations).
The drug was withdrawn following eight reports of inflammatory encephalitis and meningoencephalitis in Germany and Spain. As a result of these cases, the European Medicines Agency had announced that it was urgently reviewing Zinbryta under its Article 20 pharmacovigilance procedure.
Biogen and AbbVie stated that “characterizing the evolving benefit/risk profile of Zinbryta will not be possible going forward given the limited number of patients being treated.” Biogen said it will work with healthcare providers in managing patients treated with daclizumab.
Daclizumab was originated by Protein Design Labs (PDL) BioPharma, and developed by Roche as a transplant drug (Zenopax); its approval in 1997 made it the first humanized MAb to come to market. Zenopax was discontinued in 2009. PDL began collaborating with Biogen in 2005 to develop daclizumab in MS. The deal was one of the assets of Facet Biotech, a spin-off company created by PDL, when it was purchased by AbbVie in 2010.
A second announcement just prior to the Zinbryta withdrawal will also have an impact on MS therapeutics. Celgene Corp. announced that the FDA had issued a Refusal to File letter for ozanimod, a second-generation sphingosine-1-phosphate agent selective for the S1P1 and S1P5 receptors. Ozanimod is in development for relapsing MS.
The FDA found that the nonclinical and clinical pharmacology sections of the application were insufficient to allow a complete review. Celgene will meet with FDA officials to discuss what additional information is needed, but the setback is expected to significantly delay the launch of ozanimod. The drug was expected to obtain approval in late 2018/early 2019, but that will likely be delayed at least 9-12 months. As a result, ozanimod is now expected to be launched in the U.S. after generic fingolimod, a first-generation S1P1 agent, has come to market.