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Last updated: 19 Apr 2016

Daclizumab

Summary
Trade name: 
Zinbryta (Biogen)
(32)
Detailed results from Biogen Idec and AbbVie's pivotal Phase 3 DECIDE study further define the efficacy and safety profile of ZINBRYTA™ (daclizumab high-yield process)
Biogen Idec, 12 Sep 2014
Accessed on 15 Sep 2014 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2377&M=NewsV2&PID=61997.
(39)
Biogen Idec Becomes Biogen
Biogen, 23 Mar 2015
Accessed on 7 Apr 2015 from http://biogen.newshq.businesswire.com/press-release/corporate/biogen-idec-becomes-biogen.
Zenapax (Hoffmann-La Roche)
(16)
Daclizumab discontinue letter for the US market
Food and Drug Administration/Roche, Sep 2009
Accessed on 3 Dec 2011 from http://www.fda.gov/downloads/Drugs/DrugSafety/DrugShortages/UCM194907.pdf.
; refers to an earlier formulation used for inhibiting rejection of organ transplants, which is distinct from daclizumab high yield process (HYP)
(35)
Novel MS Drugs Advance
Gever J, MedPage Today, 4 Nov 2014
Accessed on 11 Nov 2014 from http://www.medpagetoday.com/Neurology/MultipleSclerosis/48404.
Class: 
Immunosuppressor
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
Target: 
Interleukin-2 receptor alpha (CD25) (high-affinity alpha subunit)
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
(35)
Novel MS Drugs Advance
Gever J, MedPage Today, 4 Nov 2014
Accessed on 11 Nov 2014 from http://www.medpagetoday.com/Neurology/MultipleSclerosis/48404.
T cell expansion
(5)
Current and future disease-modifying therapies in multiple sclerosis.
Lim SY, Constantinescu CS
Int J Clin Pract. 2010 Apr; 64(5):637-50. PMID: 20456216. Abstract
Innate immune system
(17)
Inhibition of LTi Cell Development by CD25 Blockade Is Associated with Decreased Intrathecal Inflammation in Multiple Sclerosis.
Perry JSA, Han S, Xu Q, Herman ML, Kennedy LB, Csako G, Bielekova B
Sci Transl Med. 2012 Aug 1; 4(145):145ra106. Epub 1969 Dec 31. PMID: 22855463. Abstract
Status for MS: 
Phase III trials for RRMS are ongoing as of 2014
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
(29)
Biogen Idec and AbbVie announce positive top-line results from Phase 3 study investigating daclizumab high-yield process in multiple sclerosis
Biogen Idec, 16 Jun 2014
Accessed on 19 Jun 2014 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2358&M=NewsV2&PID=61997.
Administration: 
Subcutaneous
(1)
Biogen Idec and Abbott Announce Enrollment of First Patient in Global Phase III Study of Daclizumab for Relapse-Remitting Multiple Sclerosis
Biogen Idec, 24 May 2010
Accessed on 3 Dec 2011 from http://www.biogenidec.com/press_release_details.aspx?ID=5981&ReqId=1430324.
Intravenous
(5)
Current and future disease-modifying therapies in multiple sclerosis.
Lim SY, Constantinescu CS
Int J Clin Pract. 2010 Apr; 64(5):637-50. PMID: 20456216. Abstract
Commercial: 
Initially marketed by Hoffman-La Roche, but withdrawn in the EU in 2008 and in the US in 2009 for commercial reasons
(15)
Withdrawal of the marketing authorization in the European Union
European Medicines Agency, 16 Jan 2009
Accessed on 3 Dec 2011 from http://www.ema.europa.eu/docs/en_GB/document_library/Public_statement/2009/11/WC500011995.pdf.
(16)
Daclizumab discontinue letter for the US market
Food and Drug Administration/Roche, Sep 2009
Accessed on 3 Dec 2011 from http://www.fda.gov/downloads/Drugs/DrugSafety/DrugShortages/UCM194907.pdf.
Trials for MS have been sponsored by Biogen Idec and AbbVie
(1)
Biogen Idec and Abbott Announce Enrollment of First Patient in Global Phase III Study of Daclizumab for Relapse-Remitting Multiple Sclerosis
Biogen Idec, 24 May 2010
Accessed on 3 Dec 2011 from http://www.biogenidec.com/press_release_details.aspx?ID=5981&ReqId=1430324.
(29)
Biogen Idec and AbbVie announce positive top-line results from Phase 3 study investigating daclizumab high-yield process in multiple sclerosis
Biogen Idec, 16 Jun 2014
Accessed on 19 Jun 2014 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2358&M=NewsV2&PID=61997.
Biogen Idec, which has sponsored trials for daclizumab in MS, has changed its name to Biogen (23 March 2015)
(39)
Biogen Idec Becomes Biogen
Biogen, 23 Mar 2015
Accessed on 7 Apr 2015 from http://biogen.newshq.businesswire.com/press-release/corporate/biogen-idec-becomes-biogen.
Marketing Authorisation Application for Zinbryta for treating relapsing forms of MS in the EU has been validated by the European Medicines Agency (EMA), a step that confirms that the submission is complete and indicates that the review process by EMA's Committee for Medicinal Products for Human Use will begin (27 March 2015)
(38)
European Medicines Agency Validates Marketing Authorisation Application for ZINBRYTA™ (Daclizumab High-Yield Process) for Treatment of MS
Biogen, 27 Mar 2015
Accessed on 7 Apr 2015 from http://biogen.newshq.businesswire.com/press-release/corporate/european-medicines-agency-validates-marketing-authorisation-application-zinb.
Biologics License Application for Zinbryta for the treatment of MS has been accepted for review by the US Food and Drug Administration (29 April 2015)
(40)
FDA Accepts Biologics License Application For ZINBRYTA (Daclizumab High-Yield Process) For Treatment of MS
Biogen, 29 Apr 2015
Accessed on 12 May 2015 from http://biogen.newshq.businesswire.com/press-release/corporate/fda-accepts-biologics-license-application-zinbryta-daclizumab-high-yield-pro.
Names
Name: 
Daclizumab
Trade name: 
Zinbryta (Biogen)
(32)
Detailed results from Biogen Idec and AbbVie's pivotal Phase 3 DECIDE study further define the efficacy and safety profile of ZINBRYTA™ (daclizumab high-yield process)
Biogen Idec, 12 Sep 2014
Accessed on 15 Sep 2014 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2377&M=NewsV2&PID=61997.
(39)
Biogen Idec Becomes Biogen
Biogen, 23 Mar 2015
Accessed on 7 Apr 2015 from http://biogen.newshq.businesswire.com/press-release/corporate/biogen-idec-becomes-biogen.
Zenapax (Hoffmann-La Roche)
(16)
Daclizumab discontinue letter for the US market
Food and Drug Administration/Roche, Sep 2009
Accessed on 3 Dec 2011 from http://www.fda.gov/downloads/Drugs/DrugSafety/DrugShortages/UCM194907.pdf.
; refers to an earlier formulation used for inhibiting rejection of organ transplants, which is distinct from daclizumab high yield process (HYP)
(35)
Novel MS Drugs Advance
Gever J, MedPage Today, 4 Nov 2014
Accessed on 11 Nov 2014 from http://www.medpagetoday.com/Neurology/MultipleSclerosis/48404.
Synonyms: 
Anti-Tac
(13)
Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey.
Waldmann TA
J Clin Immunol. 2007 Jan; 27(1):1-18. Epub 2007 Jan 11. PMID: 17216565. Abstract
DAC
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
Dacliximab
(2)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
Daclizumab
(2)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
Daclizumab high yield process
(35)
Novel MS Drugs Advance
Gever J, MedPage Today, 4 Nov 2014
Accessed on 11 Nov 2014 from http://www.medpagetoday.com/Neurology/MultipleSclerosis/48404.
Daclizumab HYP
(35)
Novel MS Drugs Advance
Gever J, MedPage Today, 4 Nov 2014
Accessed on 11 Nov 2014 from http://www.medpagetoday.com/Neurology/MultipleSclerosis/48404.
Ro 24-7375
(2)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
UNII-CUJ2MVI71Y
(2)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
Systematic name: 
Immunoglobulin G 1 (human-mouse monoclonal clone 1H4 gamma-chain anti- human interleukin 2 receptor), disulfide with human-mouse monoclonal clone 1H4 light chain, dimer
(2)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
Physiology
Class: 
Immunosuppressor
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
Target: 
Interleukin-2 receptor alpha (CD25) (high-affinity alpha subunit)
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
(35)
Novel MS Drugs Advance
Gever J, MedPage Today, 4 Nov 2014
Accessed on 11 Nov 2014 from http://www.medpagetoday.com/Neurology/MultipleSclerosis/48404.
T cell expansion
(5)
Current and future disease-modifying therapies in multiple sclerosis.
Lim SY, Constantinescu CS
Int J Clin Pract. 2010 Apr; 64(5):637-50. PMID: 20456216. Abstract
Innate immune system
(17)
Inhibition of LTi Cell Development by CD25 Blockade Is Associated with Decreased Intrathecal Inflammation in Multiple Sclerosis.
Perry JSA, Han S, Xu Q, Herman ML, Kennedy LB, Csako G, Bielekova B
Sci Transl Med. 2012 Aug 1; 4(145):145ra106. Epub 1969 Dec 31. PMID: 22855463. Abstract
Properties: 
Recombinant humanized monoclonal antibody
(3)
FDA product review for daclizumab
Food and Drug Administration, 4 Dec 1997
Accessed on 3 Dec 2011 from http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/UCM272414.pdf.
IgG
(1)
Biogen Idec and Abbott Announce Enrollment of First Patient in Global Phase III Study of Daclizumab for Relapse-Remitting Multiple Sclerosis
Biogen Idec, 24 May 2010
Accessed on 3 Dec 2011 from http://www.biogenidec.com/press_release_details.aspx?ID=5981&ReqId=1430324.
Comprised of four subunits, two heavy chains and two light chains, with all four chains linked via disulfide bridges
(1)
Biogen Idec and Abbott Announce Enrollment of First Patient in Global Phase III Study of Daclizumab for Relapse-Remitting Multiple Sclerosis
Biogen Idec, 24 May 2010
Accessed on 3 Dec 2011 from http://www.biogenidec.com/press_release_details.aspx?ID=5981&ReqId=1430324.
Dimer
(1)
Biogen Idec and Abbott Announce Enrollment of First Patient in Global Phase III Study of Daclizumab for Relapse-Remitting Multiple Sclerosis
Biogen Idec, 24 May 2010
Accessed on 3 Dec 2011 from http://www.biogenidec.com/press_release_details.aspx?ID=5981&ReqId=1430324.
Molecular weight, ~150 kDa
(3)
FDA product review for daclizumab
Food and Drug Administration, 4 Dec 1997
Accessed on 3 Dec 2011 from http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/UCM272414.pdf.
DNA sequence is 90% human origin and 10% mouse origin
(1)
Biogen Idec and Abbott Announce Enrollment of First Patient in Global Phase III Study of Daclizumab for Relapse-Remitting Multiple Sclerosis
Biogen Idec, 24 May 2010
Accessed on 3 Dec 2011 from http://www.biogenidec.com/press_release_details.aspx?ID=5981&ReqId=1430324.
Contains approximately 2% carbohydrate by weight
(1)
Biogen Idec and Abbott Announce Enrollment of First Patient in Global Phase III Study of Daclizumab for Relapse-Remitting Multiple Sclerosis
Biogen Idec, 24 May 2010
Accessed on 3 Dec 2011 from http://www.biogenidec.com/press_release_details.aspx?ID=5981&ReqId=1430324.
Saturates activated T cells by 10 hours post-infusion; cells remain saturated for 64 days when the drug is given at 5 mg per kg
(3)
FDA product review for daclizumab
Food and Drug Administration, 4 Dec 1997
Accessed on 3 Dec 2011 from http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/UCM272414.pdf.
Pharmacokinetics have been evaluated in healthy volunteers in three double-blind, placebo-controlled trials after single- and multiple-dose subcutaneous and single-dose intravenous administration, and serum concentrations from these studies have been analyzed with nonlinear mixed-effects modeling
(33)
Population pharmacokinetics of daclizumab high-yield process in healthy volunteers: integrated analysis of intravenous and subcutaneous, single- and multiple-dose administration.
Othman AA, Tran JQ, Tang MT, Dutta S
Clin Pharmacokinet. 2014 Oct; 53(10):907-18. PMID: 25212703. Abstract
Pharmacokinetics/pharmacodynamics have been studied in individuals with adult T-cell leukemia/lymphoma (ATL); whereas saturation of CD25 on the surface of circulating ATL cells occurred at all doses studied, a high dose of 8 mg per kg (which was well tolerated) was required for saturation on ATL cells in lymph nodes, suggesting that such higher doses would be more effective in MS as well
(34)
Safety, efficacy, and pharmacokinetics/pharmacodynamics of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma.
Berkowitz JL, Janik JE, Stewart DM, Jaffe ES, Stetler-Stevenson M, Shih JH, Fleisher TA, Turner M, Urquhart NE, Wharfe GH, et al.
Clin Immunol. 2014 Sep 28. PMID: 25267440. Abstract
Undergoes slow clearance, as shown by studies in healthy volunteers
(33)
Population pharmacokinetics of daclizumab high-yield process in healthy volunteers: integrated analysis of intravenous and subcutaneous, single- and multiple-dose administration.
Othman AA, Tran JQ, Tang MT, Dutta S
Clin Pharmacokinet. 2014 Oct; 53(10):907-18. PMID: 25212703. Abstract
Undergoes slow clearance in individuals with RRMS, as shown by analysis of data from Phase II and Phase III trials
(49)
Population Pharmacokinetics of Daclizumab High-Yield Process in Healthy Volunteers and Subjects with Multiple Sclerosis: Analysis of Phase I-III Clinical Trials.
Diao L, Hang Y, Othman AA, Nestorov I, Tran JQ
Clin Pharmacokinet. 2016 Feb 12. PMID: 26873229. Abstract
At doses ≥100 mg, exhibits linear pharmacokinetics, as shown by studies in healthy volunteers
(33)
Population pharmacokinetics of daclizumab high-yield process in healthy volunteers: integrated analysis of intravenous and subcutaneous, single- and multiple-dose administration.
Othman AA, Tran JQ, Tang MT, Dutta S
Clin Pharmacokinet. 2014 Oct; 53(10):907-18. PMID: 25212703. Abstract
At doses >100 mg, exhibits linear pharmacokinetics in individuals with RRMS, as shown by analysis of data from Phase II and Phase III trials
(49)
Population Pharmacokinetics of Daclizumab High-Yield Process in Healthy Volunteers and Subjects with Multiple Sclerosis: Analysis of Phase I-III Clinical Trials.
Diao L, Hang Y, Othman AA, Nestorov I, Tran JQ
Clin Pharmacokinet. 2016 Feb 12. PMID: 26873229. Abstract
Expected to saturate CD25 on target T cells within several hours at a dose of 150 mg once per month, and to then maintain this saturation until the next dose, based on nonlinear mixed-effects modeling of pharmacokinetic measurements from Phase I studies
(43)
Blockade of the High-Affinity Interleukin-2 Receptors with Daclizumab High-Yield Process: Pharmacokinetic/Pharmacodynamic Analysis of Single- and Multiple-Dose Phase I Trials.
Minocha M, Tran JQ, Sheridan JP, Othman AA
Clin Pharmacokinet. 2015 Aug 5. PMID: 26242380. Abstract
Expected to saturate CD25 on target T cells at a dose of 150 mg once per month; 4 to 6 months after the last dose, free CD25 levels are expected to return to baseline levels, based on nonlinear mixed-effects modeling of pharmacokinetic measurements from Phase I studies
(43)
Blockade of the High-Affinity Interleukin-2 Receptors with Daclizumab High-Yield Process: Pharmacokinetic/Pharmacodynamic Analysis of Single- and Multiple-Dose Phase I Trials.
Minocha M, Tran JQ, Sheridan JP, Othman AA
Clin Pharmacokinet. 2015 Aug 5. PMID: 26242380. Abstract
Bioavailability after subcutaneous administration is high (84%) in healthy volunteers
(33)
Population pharmacokinetics of daclizumab high-yield process in healthy volunteers: integrated analysis of intravenous and subcutaneous, single- and multiple-dose administration.
Othman AA, Tran JQ, Tang MT, Dutta S
Clin Pharmacokinet. 2014 Oct; 53(10):907-18. PMID: 25212703. Abstract
Estimated effective half-life is 21 to 25 days and is thus suitable for monthly administration, as shown by studies in healthy volunteers
(33)
Population pharmacokinetics of daclizumab high-yield process in healthy volunteers: integrated analysis of intravenous and subcutaneous, single- and multiple-dose administration.
Othman AA, Tran JQ, Tang MT, Dutta S
Clin Pharmacokinet. 2014 Oct; 53(10):907-18. PMID: 25212703. Abstract
Has a terminal half-life of 21 days in individuals with RRMS, as shown by analysis of data from Phase II and Phase III trials
(49)
Population Pharmacokinetics of Daclizumab High-Yield Process in Healthy Volunteers and Subjects with Multiple Sclerosis: Analysis of Phase I-III Clinical Trials.
Diao L, Hang Y, Othman AA, Nestorov I, Tran JQ
Clin Pharmacokinet. 2016 Feb 12. PMID: 26873229. Abstract
Exhibits high subcutaneous bioavailability in individuals with RRMS, as shown by analysis of data from Phase II and Phase III trials
(49)
Population Pharmacokinetics of Daclizumab High-Yield Process in Healthy Volunteers and Subjects with Multiple Sclerosis: Analysis of Phase I-III Clinical Trials.
Diao L, Hang Y, Othman AA, Nestorov I, Tran JQ
Clin Pharmacokinet. 2016 Feb 12. PMID: 26873229. Abstract
Pharmacokinetics have been determined in individuals with RRMS receiving a 150 mg subcutaneous dose every 4 weeks
(50)
Pharmacokinetics of daclizumab high-yield process with repeated administration of the clinical subcutaneous regimen in patients with relapsing-remitting multiple sclerosis.
Tran JQ, Othman AA, Mikulskis A, Wolstencroft P, Elkins J
Clin Pharmacol. 2016; 8:9-13. Epub 2016 Feb 11. PMID: 26929672. Abstract
Exhibits slow absorption when administered as a 150 mg subcutaneous dose every 4 weeks, such that the median time to reach the maximum observed concentration is about 1 week, as shown in a study of 26 individuals with RRMS
(50)
Pharmacokinetics of daclizumab high-yield process with repeated administration of the clinical subcutaneous regimen in patients with relapsing-remitting multiple sclerosis.
Tran JQ, Othman AA, Mikulskis A, Wolstencroft P, Elkins J
Clin Pharmacol. 2016; 8:9-13. Epub 2016 Feb 11. PMID: 26929672. Abstract
Reaches a steady state by the fourth injection when administered as a 150 mg subcutaneous dose every 4 weeks, as shown in a study of 26 individuals with RRMS
(50)
Pharmacokinetics of daclizumab high-yield process with repeated administration of the clinical subcutaneous regimen in patients with relapsing-remitting multiple sclerosis.
Tran JQ, Othman AA, Mikulskis A, Wolstencroft P, Elkins J
Clin Pharmacol. 2016; 8:9-13. Epub 2016 Feb 11. PMID: 26929672. Abstract

Mechanisms/Effects

Human: 
Exact mechanism is not well understood
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
Interrupts interleukin-2-mediated cell activation, thereby preventing expansion of autoreactive T lymphocytes
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
(5)
Current and future disease-modifying therapies in multiple sclerosis.
Lim SY, Constantinescu CS
Int J Clin Pract. 2010 Apr; 64(5):637-50. PMID: 20456216. Abstract
Stimulates production and enhances function of CD56 (bright) natural killer cells in patients; in vitro, this inhibits survival of activated T cells
(8)
Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta.
Wynn D, Kaufman M, Montalban X, Vollmer T, Simon J, Elkins J, O'Neill G, Neyer L, Sheridan J, Wang C, et al.
Lancet Neurol. 2010 Apr; 9(4):381-90. Epub 2010 Feb 15. PMID: 20163990. Abstract
(12)
Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis.
Bielekova B, Catalfamo M, Reichert-Scrivner S, Packer A, Cerna M, Waldmann TA, McFarland H, Henkart PA, Martin R
Proc Natl Acad Sci U S A. 2006 Apr 11; 103(15):5941-6. Epub 2006 Apr 03. PMID: 16585503. Abstract
Increases the number of CD56(bright) natural killer cells, as shown in the 52-week SELECT trial, and the numbers of such cells early in the course of treatment correlate with the number of new or newly enlarging T2-hyperintense lesions later during the first year of therapy
(37)
CD56(bright) natural killer cells and response to daclizumab HYP in relapsing-remitting MS.
Elkins J, Sheridan J, Amaravadi L, Riester K, Selmaj K, Bielekova B, Parr E, Giovannoni G
Neurol Neuroimmunol Neuroinflamm. 2015 Apr; 2(2):e65. Epub 2015 Jan 22. PMID: 25635261. Abstract
May inhibit CD40L expression
(6)
Long-term daclizumab therapy in relapsing-remitting multiple sclerosis.
Rojas MA, Carlson NG, Miller TL, Rose JW
Ther Adv Neurol Disord. 2009 Sep; 2(5):291-7. PMID: 21180619. Abstract
Reduces regulatory T cell frequency and function, based on blood and cerebrospinal fluid samples in 15 patients
(9)
Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis.
Bielekova B, Howard T, Packer AN, Richert N, Blevins G, Ohayon J, Waldmann TA, McFarland HF, Martin R
Arch Neurol. 2009 Apr; 66(4):483-9. PMID: 19364933. Abstract
Reduces levels of regulatory T cells by ~50% over a 52-week period in individuals with RRMS; this decrease is not linked with daclizumab-associated clinical benefit
(36)
In Vivo Maintenance of Human Regulatory T Cells during CD25 Blockade.
Huss DJ, Mehta DS, Sharma A, You X, Riester KA, Sheridan JP, Amaravadi LS, Elkins JS, Fontenot JD
J Immunol. 2014 Nov 21. PMID: 25416807. Abstract
Reduces levels of regulatory T cells (Tregs, which express FOXP3) by ~50% over a 52-week period in individuals with RRMS; FOXP3+ cells that remain exhibit a demethylated region specific for Tregs in the FOXP3 promoter, undergo cell cycling, and display little production of interleukin-2 (IL-2), interferon-gamma, and IL-17, showing that the Treg lineage is maintained during daclizumab therapy
(36)
In Vivo Maintenance of Human Regulatory T Cells during CD25 Blockade.
Huss DJ, Mehta DS, Sharma A, You X, Riester KA, Sheridan JP, Amaravadi LS, Elkins JS, Fontenot JD
J Immunol. 2014 Nov 21. PMID: 25416807. Abstract
Increases serum concentrations of interleukin-2 (IL-2), and signaling through the intermediate-affinity receptor IL-2Rβγ causes STAT5 phosphorylation and FOXP3 expression, in individuals with RRMS
(36)
In Vivo Maintenance of Human Regulatory T Cells during CD25 Blockade.
Huss DJ, Mehta DS, Sharma A, You X, Riester KA, Sheridan JP, Amaravadi LS, Elkins JS, Fontenot JD
J Immunol. 2014 Nov 21. PMID: 25416807. Abstract
Decreases the number of circulating innate lymphoid cells (which is elevated in untreated MS patients)
(17)
Inhibition of LTi Cell Development by CD25 Blockade Is Associated with Decreased Intrathecal Inflammation in Multiple Sclerosis.
Perry JSA, Han S, Xu Q, Herman ML, Kennedy LB, Csako G, Bielekova B
Sci Transl Med. 2012 Aug 1; 4(145):145ra106. Epub 1969 Dec 31. PMID: 22855463. Abstract
Modifies the phenotype of innate lymphoid cells from inflammation-promoting lymphoid tissue inducer cells toward immunoregulatory natural killer cells via a mechanism that involves interleukin-2 signaling
(17)
Inhibition of LTi Cell Development by CD25 Blockade Is Associated with Decreased Intrathecal Inflammation in Multiple Sclerosis.
Perry JSA, Han S, Xu Q, Herman ML, Kennedy LB, Csako G, Bielekova B
Sci Transl Med. 2012 Aug 1; 4(145):145ra106. Epub 1969 Dec 31. PMID: 22855463. Abstract
Inhibits intrathecal inflammation in MS patients, as determined by measuring cerebrospinal fluid levels of chemokine (C-X-C motif) ligand 13, which is associated with lymphoid neogenesis, and immunoglobulin G (IgG) index, a measure of intrathecal IgG production
(17)
Inhibition of LTi Cell Development by CD25 Blockade Is Associated with Decreased Intrathecal Inflammation in Multiple Sclerosis.
Perry JSA, Han S, Xu Q, Herman ML, Kennedy LB, Csako G, Bielekova B
Sci Transl Med. 2012 Aug 1; 4(145):145ra106. Epub 1969 Dec 31. PMID: 22855463. Abstract
Reduces cell surface levels of CD25 on activated T cells in vitro through a mechanism involving trogocytosis mediated by monocytes
(23)
Daclizumab reduces CD25 levels on T cells through monocyte-mediated trogocytosis.
Zhang Y, McClellan M, Efros L, Shi D, Bielekova B, Tang M, Vexler V, Sheridan J
Mult Scler. 2013 Jul 11. PMID: 23846354. Abstract
Long-term treatment reverses the intrathecal enrichment of Epstein-Barr virus- and human herpes virus 6-specific T cell reactivities that occurs in individuals with RRMS
(31)
A complex role of herpes viruses in the disease process of multiple sclerosis.
Wuest SC, Mexhitaj I, Chai N R, Romm E, Scheffel J, Xu B, Lane K, Wu T, Bielekova B
PLoS One. 2014; 9(8):e105434. Epub 2014 Aug 22. PMID: 25148387. Abstract
Long-term therapy normalizes the abnormalities in immune cell subpopulations in the cerebrospinal fluid in individuals with RRMS, as shown by analysis of treated and untreated individuals with RRMS and healthy donors
(41)
Daclizumab reverses intrathecal immune cell abnormalities in multiple sclerosis.
Lin Y C, Winokur P, Blake A, Wu T, Romm E, Bielekova B
Ann Clin Transl Neurol. 2015 May; 2(5):445-55. Epub 2015 Apr 07. PMID: 26000318. Abstract
Long-term therapy reverses the strong enrichment of CD4+ and CD8+ T cells and B cells in the cerebrospinal fluid that occurs in untreated individuals with RRMS, as shown by analysis of treated and untreated individuals with RRMS and healthy donors
(41)
Daclizumab reverses intrathecal immune cell abnormalities in multiple sclerosis.
Lin Y C, Winokur P, Blake A, Wu T, Romm E, Bielekova B
Ann Clin Transl Neurol. 2015 May; 2(5):445-55. Epub 2015 Apr 07. PMID: 26000318. Abstract
Long-term therapy reverses increases in innate lymphoid cells and lymphoid tissue inducer cells in the cerebrospinal fluid and blood that occur in untreated individuals with RRMS, as shown by analysis of treated and untreated individuals with RRMS and healthy donors
(41)
Daclizumab reverses intrathecal immune cell abnormalities in multiple sclerosis.
Lin Y C, Winokur P, Blake A, Wu T, Romm E, Bielekova B
Ann Clin Transl Neurol. 2015 May; 2(5):445-55. Epub 2015 Apr 07. PMID: 26000318. Abstract
Long-term therapy increases the reduced proportion of monocytes in the cerebrospinal fluid that occurs in untreated individuals with RRMS, as shown by analysis of treated and untreated individuals with RRMS and healthy donors
(41)
Daclizumab reverses intrathecal immune cell abnormalities in multiple sclerosis.
Lin Y C, Winokur P, Blake A, Wu T, Romm E, Bielekova B
Ann Clin Transl Neurol. 2015 May; 2(5):445-55. Epub 2015 Apr 07. PMID: 26000318. Abstract
Long-term therapy leads to an expansion of CD56(bright) natural killer cells in individuals with RRMS, a marker that distinguishes them from healthy donors
(41)
Daclizumab reverses intrathecal immune cell abnormalities in multiple sclerosis.
Lin Y C, Winokur P, Blake A, Wu T, Romm E, Bielekova B
Ann Clin Transl Neurol. 2015 May; 2(5):445-55. Epub 2015 Apr 07. PMID: 26000318. Abstract
Does not affect influenza vaccine-induced antibody responses or expansion of memory B cells, as shown in a study of 23 daclizumab-treated individuals with MS after seasonal influenza vaccination (Afluria vaccine)
(47)
Patients with MS under daclizumab therapy mount normal immune responses to influenza vaccination.
Lin Y C, Winokur P, Blake A, Wu T, Manischewitz J, King LR, Romm E, Golding H, Bielekova B
Neurol Neuroimmunol Neuroinflamm. 2016 Feb; 3(1):e196. Epub 2016 Jan 27. PMID: 26848487. Abstract
Does not affect the activity of cytochrome P450 enzymes (CYP1A2, 2C9, 2C19, 2D6, and 3A), as shown in a study in which individuals with MS being treated with daclizumab were given an oral cocktail of probe substrates of these enzymes
(51)
Therapeutic protein-drug interaction assessment for daclizumab high-yield process in patients with multiple sclerosis using a cocktail approach.
Tran JQ, Othman AA, Wolstencroft P, Elkins J
Br J Clin Pharmacol. 2016 Mar 17. PMID: 26991517. Abstract
Regulatory and Commercial Status
Status for MS: 
Phase III trials for RRMS are ongoing as of 2014
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
(29)
Biogen Idec and AbbVie announce positive top-line results from Phase 3 study investigating daclizumab high-yield process in multiple sclerosis
Biogen Idec, 16 Jun 2014
Accessed on 19 Jun 2014 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2358&M=NewsV2&PID=61997.
Highest status achieved (for any condition): 
Approved by the US Food and Drug Administration in 1997 for acute organ rejection in renal transplantation
(14)
FDA approval letter for daclizumab for the prophylaxis of acute organ rejection in patients receiving renal transplants
Food and Drug Administration, 10 Dec 1997
Accessed on 3 Dec 2011 from http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm113466.pdf.
Other uses: 
Renal graft rejection
(13)
Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey.
Waldmann TA
J Clin Immunol. 2007 Jan; 27(1):1-18. Epub 2007 Jan 11. PMID: 17216565. Abstract
Adult T cell leukemia
(13)
Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey.
Waldmann TA
J Clin Immunol. 2007 Jan; 27(1):1-18. Epub 2007 Jan 11. PMID: 17216565. Abstract
HTLV-I associated myelopathy/tropical spastic paraparesis
(13)
Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey.
Waldmann TA
J Clin Immunol. 2007 Jan; 27(1):1-18. Epub 2007 Jan 11. PMID: 17216565. Abstract
HAM/TSP
(13)
Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey.
Waldmann TA
J Clin Immunol. 2007 Jan; 27(1):1-18. Epub 2007 Jan 11. PMID: 17216565. Abstract
Noninfectious uveitis
(13)
Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey.
Waldmann TA
J Clin Immunol. 2007 Jan; 27(1):1-18. Epub 2007 Jan 11. PMID: 17216565. Abstract
Pure red cell aplasia
(13)
Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey.
Waldmann TA
J Clin Immunol. 2007 Jan; 27(1):1-18. Epub 2007 Jan 11. PMID: 17216565. Abstract
Aplastic anemia
(13)
Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey.
Waldmann TA
J Clin Immunol. 2007 Jan; 27(1):1-18. Epub 2007 Jan 11. PMID: 17216565. Abstract
Administration: 
Subcutaneous
(1)
Biogen Idec and Abbott Announce Enrollment of First Patient in Global Phase III Study of Daclizumab for Relapse-Remitting Multiple Sclerosis
Biogen Idec, 24 May 2010
Accessed on 3 Dec 2011 from http://www.biogenidec.com/press_release_details.aspx?ID=5981&ReqId=1430324.
Intravenous
(5)
Current and future disease-modifying therapies in multiple sclerosis.
Lim SY, Constantinescu CS
Int J Clin Pract. 2010 Apr; 64(5):637-50. PMID: 20456216. Abstract
Negative effects: 
Has been associated with adverse events in multiple organ systems
(27)
Daclizumab-induced adverse events in multiple organ systems in multiple sclerosis.
Oh J, Saidha S, Cortese I, Ohayon J, Bielekova B, Calabresi PA, Newsome SD
Neurology. 2014 Feb 14. PMID: 24532277. Abstract
Alopecia
(27)
Daclizumab-induced adverse events in multiple organ systems in multiple sclerosis.
Oh J, Saidha S, Cortese I, Ohayon J, Bielekova B, Calabresi PA, Newsome SD
Neurology. 2014 Feb 14. PMID: 24532277. Abstract
Autoimmune attacks (hepatic and renal)
(18)
Safety issue puts daclizumab in doubt for MS
Medpage Today, 15 Oct 2012
Accessed on 1 Nov 2012 from http://www.medpagetoday.com/MeetingCoverage/ECTRIMS/35315.
Transient formation of autoantibodies requiring corticosteroid therapy
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
Breast nodules
(27)
Daclizumab-induced adverse events in multiple organ systems in multiple sclerosis.
Oh J, Saidha S, Cortese I, Ohayon J, Bielekova B, Calabresi PA, Newsome SD
Neurology. 2014 Feb 14. PMID: 24532277. Abstract
Cardiotoxicity
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
Central nervous system vasculitis developed in one treated MS patient
(19)
CNS vasculitis in a patient with MS on daclizumab monotherapy.
Ohayon J, Oh U, Richert N, Martin J, Vortmeyer A, McFarland H, Bielekova B
Neurology. 2013 Jan 9. PMID: 23303850. Abstract
Chest discomfort
(5)
Current and future disease-modifying therapies in multiple sclerosis.
Lim SY, Constantinescu CS
Int J Clin Pract. 2010 Apr; 64(5):637-50. PMID: 20456216. Abstract
Severe cutaneous events and reactions
(32)
Detailed results from Biogen Idec and AbbVie's pivotal Phase 3 DECIDE study further define the efficacy and safety profile of ZINBRYTA™ (daclizumab high-yield process)
Biogen Idec, 12 Sep 2014
Accessed on 15 Sep 2014 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2377&M=NewsV2&PID=61997.
(35)
Novel MS Drugs Advance
Gever J, MedPage Today, 4 Nov 2014
Accessed on 11 Nov 2014 from http://www.medpagetoday.com/Neurology/MultipleSclerosis/48404.
Associated with cutaneous adverse events that exhibit nonspecific signs of eczematous dermatitis and contain infiltrates of CD56+ lymphoid cells, regardless of clinical severity
(48)
Cutaneous adverse events in multiple sclerosis patients treated with daclizumab.
Cortese I, Ohayon J, Fenton K, Lee C-C, Raffeld M, Cowen EW, DiGiovanna JJ, Bielekova B
Neurology. 2016 Feb 3. PMID: 26843560. Abstract
Fatigue
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
Fever
(5)
Current and future disease-modifying therapies in multiple sclerosis.
Lim SY, Constantinescu CS
Int J Clin Pract. 2010 Apr; 64(5):637-50. PMID: 20456216. Abstract
Gastrointestinal symptoms
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
Generalized weakness
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
Hepatotoxicity
(35)
Novel MS Drugs Advance
Gever J, MedPage Today, 4 Nov 2014
Accessed on 11 Nov 2014 from http://www.medpagetoday.com/Neurology/MultipleSclerosis/48404.
Hypersensitivity
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
Severe infections
(8)
Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta.
Wynn D, Kaufman M, Montalban X, Vollmer T, Simon J, Elkins J, O'Neill G, Neyer L, Sheridan J, Wang C, et al.
Lancet Neurol. 2010 Apr; 9(4):381-90. Epub 2010 Feb 15. PMID: 20163990. Abstract
Infusion reaction
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
Elevations of liver transaminases
(32)
Detailed results from Biogen Idec and AbbVie's pivotal Phase 3 DECIDE study further define the efficacy and safety profile of ZINBRYTA™ (daclizumab high-yield process)
Biogen Idec, 12 Sep 2014
Accessed on 15 Sep 2014 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2377&M=NewsV2&PID=61997.
Diffuse lymphadenopathy
(27)
Daclizumab-induced adverse events in multiple organ systems in multiple sclerosis.
Oh J, Saidha S, Cortese I, Ohayon J, Bielekova B, Calabresi PA, Newsome SD
Neurology. 2014 Feb 14. PMID: 24532277. Abstract
Mouth ulcers
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
Psoriasis in an individual with a positive family history
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
Diffuse rash
(27)
Daclizumab-induced adverse events in multiple organ systems in multiple sclerosis.
Oh J, Saidha S, Cortese I, Ohayon J, Bielekova B, Calabresi PA, Newsome SD
Neurology. 2014 Feb 14. PMID: 24532277. Abstract
Viral meningitis
(4)
Treating multiple sclerosis with monoclonal antibodies: a 2010 update.
Buttmann M
Expert Rev Neurother. 2010 May; 10(5):791-809. PMID: 20420497. Abstract
Commercial: 
Initially marketed by Hoffman-La Roche, but withdrawn in the EU in 2008 and in the US in 2009 for commercial reasons
(15)
Withdrawal of the marketing authorization in the European Union
European Medicines Agency, 16 Jan 2009
Accessed on 3 Dec 2011 from http://www.ema.europa.eu/docs/en_GB/document_library/Public_statement/2009/11/WC500011995.pdf.
(16)
Daclizumab discontinue letter for the US market
Food and Drug Administration/Roche, Sep 2009
Accessed on 3 Dec 2011 from http://www.fda.gov/downloads/Drugs/DrugSafety/DrugShortages/UCM194907.pdf.
Trials for MS have been sponsored by Biogen Idec and AbbVie
(1)
Biogen Idec and Abbott Announce Enrollment of First Patient in Global Phase III Study of Daclizumab for Relapse-Remitting Multiple Sclerosis
Biogen Idec, 24 May 2010
Accessed on 3 Dec 2011 from http://www.biogenidec.com/press_release_details.aspx?ID=5981&ReqId=1430324.
(29)
Biogen Idec and AbbVie announce positive top-line results from Phase 3 study investigating daclizumab high-yield process in multiple sclerosis
Biogen Idec, 16 Jun 2014
Accessed on 19 Jun 2014 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2358&M=NewsV2&PID=61997.
Biogen Idec, which has sponsored trials for daclizumab in MS, has changed its name to Biogen (23 March 2015)
(39)
Biogen Idec Becomes Biogen
Biogen, 23 Mar 2015
Accessed on 7 Apr 2015 from http://biogen.newshq.businesswire.com/press-release/corporate/biogen-idec-becomes-biogen.
Marketing Authorisation Application for Zinbryta for treating relapsing forms of MS in the EU has been validated by the European Medicines Agency (EMA), a step that confirms that the submission is complete and indicates that the review process by EMA's Committee for Medicinal Products for Human Use will begin (27 March 2015)
(38)
European Medicines Agency Validates Marketing Authorisation Application for ZINBRYTA™ (Daclizumab High-Yield Process) for Treatment of MS
Biogen, 27 Mar 2015
Accessed on 7 Apr 2015 from http://biogen.newshq.businesswire.com/press-release/corporate/european-medicines-agency-validates-marketing-authorisation-application-zinb.
Biologics License Application for Zinbryta for the treatment of MS has been accepted for review by the US Food and Drug Administration (29 April 2015)
(40)
FDA Accepts Biologics License Application For ZINBRYTA (Daclizumab High-Yield Process) For Treatment of MS
Biogen, 29 Apr 2015
Accessed on 12 May 2015 from http://biogen.newshq.businesswire.com/press-release/corporate/fda-accepts-biologics-license-application-zinbryta-daclizumab-high-yield-pro.
Key Clinical Trials
Placebo-controlled Trials: 
Trial name: 
Safety and Efficacy Study of Daclizumab HYP to Treat Relapsing-Remitting Multiple Sclerosis (SELECT) (results reported 2011, publ 2013)
(7)
Biogen Idec and Abbott Announce Positive Top-Line Results from the First Registrational Trial for Daclizumab HYP in relapsing-Remitting Multiple Sclerosis
Biogen Idec, 9 Aug 2011
Accessed on 3 Dec 2011 from http://www.biogenidec.com/PRESS_RELEASE_DETAILS.aspx?ID=5981&ReqId=1594585.
(20)
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial.
Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue E-W, Stefoski D, Robinson R, Riester K, Rana J, et al.
Lancet. 2013 Apr 3. Epub 1969 Dec 31. PMID: 23562009. Abstract
(24)
Disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with daclizumab high-yield process in the SELECT study.
Havrdova E, Giovannoni G, Stefoski D, Forster S, Umans K, Mehta L, Greenberg S, Elkins J
Mult Scler. 2013 Sep 10. PMID: 24022270. Abstract
(26)
Effect of daclizumab high-yield process in patients with highly active relapsing-remitting multiple sclerosis.
Giovannoni G, Radue E-W, Havrdova E, Riester K, Greenberg S, Mehta L, Elkins J
J Neurol. 2013 Dec 29. PMID: 24375015. Abstract
(52)
Assessing the impact of multiple sclerosis disease activity and daclizumab HYP treatment on patient-reported outcomes: Results from the SELECT trial.
Phillips G, Guo S, Bender R, Havrdová E, Proskorovsky I, Vollmer T
Mult Scler Relat Disord. 2016 Mar; 6:66-72. Epub 2016 Feb 01. PMID: 27063626. Abstract
Phase: 
Phase IIb trial
(7)
Biogen Idec and Abbott Announce Positive Top-Line Results from the First Registrational Trial for Daclizumab HYP in relapsing-Remitting Multiple Sclerosis
Biogen Idec, 9 Aug 2011
Accessed on 3 Dec 2011 from http://www.biogenidec.com/PRESS_RELEASE_DETAILS.aspx?ID=5981&ReqId=1594585.
Study Design: 
Company-sponsored, randomized, double-blind, placebo-controlled, multinational, multicenter trial to evaluate the efficacy of two doses (150 mg or 300 mg) of daclizumab high-yield process (HYP), given subcutaneously every 4 weeks for 52 weeks, on the annualized relapse rate (primary endpoint)
(7)
Biogen Idec and Abbott Announce Positive Top-Line Results from the First Registrational Trial for Daclizumab HYP in relapsing-Remitting Multiple Sclerosis
Biogen Idec, 9 Aug 2011
Accessed on 3 Dec 2011 from http://www.biogenidec.com/PRESS_RELEASE_DETAILS.aspx?ID=5981&ReqId=1594585.
(20)
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial.
Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue E-W, Stefoski D, Robinson R, Riester K, Rana J, et al.
Lancet. 2013 Apr 3. Epub 1969 Dec 31. PMID: 23562009. Abstract
Disease Stage: 
RRMS
(7)
Biogen Idec and Abbott Announce Positive Top-Line Results from the First Registrational Trial for Daclizumab HYP in relapsing-Remitting Multiple Sclerosis
Biogen Idec, 9 Aug 2011
Accessed on 3 Dec 2011 from http://www.biogenidec.com/PRESS_RELEASE_DETAILS.aspx?ID=5981&ReqId=1594585.
(20)
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial.
Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue E-W, Stefoski D, Robinson R, Riester K, Rana J, et al.
Lancet. 2013 Apr 3. Epub 1969 Dec 31. PMID: 23562009. Abstract
Enrollment/Number of Patients: 
621, with over 90% completing the study
(20)
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial.
Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue E-W, Stefoski D, Robinson R, Riester K, Rana J, et al.
Lancet. 2013 Apr 3. Epub 1969 Dec 31. PMID: 23562009. Abstract
Duration: 
1 year
(7)
Biogen Idec and Abbott Announce Positive Top-Line Results from the First Registrational Trial for Daclizumab HYP in relapsing-Remitting Multiple Sclerosis
Biogen Idec, 9 Aug 2011
Accessed on 3 Dec 2011 from http://www.biogenidec.com/PRESS_RELEASE_DETAILS.aspx?ID=5981&ReqId=1594585.
(20)
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial.
Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue E-W, Stefoski D, Robinson R, Riester K, Rana J, et al.
Lancet. 2013 Apr 3. Epub 1969 Dec 31. PMID: 23562009. Abstract
Status/Outcome: 
Compared to placebo, daclizumab HYP was associated with a lower annualized relapse rate (0.21 for the 150 mg dose and 0.23 for the 300 mg dose versus 0.46 for placebo, representing 54% and 50% reductions for the two doses, respectively), and a reduction in cumulative number of gadolinium-enhancing lesions between weeks 8 and 24, a reduction in number of newly enlarging T2 hyperintense lesions at one year, and reduction in proportion of individuals who relapsed
(7)
Biogen Idec and Abbott Announce Positive Top-Line Results from the First Registrational Trial for Daclizumab HYP in relapsing-Remitting Multiple Sclerosis
Biogen Idec, 9 Aug 2011
Accessed on 3 Dec 2011 from http://www.biogenidec.com/PRESS_RELEASE_DETAILS.aspx?ID=5981&ReqId=1594585.
(20)
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial.
Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue E-W, Stefoski D, Robinson R, Riester K, Rana J, et al.
Lancet. 2013 Apr 3. Epub 1969 Dec 31. PMID: 23562009. Abstract
; three cases of autoimmune attacks (hepatic and renal) occurred
(18)
Safety issue puts daclizumab in doubt for MS
Medpage Today, 15 Oct 2012
Accessed on 1 Nov 2012 from http://www.medpagetoday.com/MeetingCoverage/ECTRIMS/35315.
; further analysis showed that at 1 year, daclizumab HYP was associated with an increase in the percentage of individuals who were free of disease activity (39% versus 11% of those receiving placebo), as defined by both clinical and radiological criteria
(24)
Disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with daclizumab high-yield process in the SELECT study.
Havrdova E, Giovannoni G, Stefoski D, Forster S, Umans K, Mehta L, Greenberg S, Elkins J
Mult Scler. 2013 Sep 10. PMID: 24022270. Abstract
; posthoc analysis showed that daclizumab HYP had similar effects in individuals with highly active versus less active RRMS (disease activity was assessed before treatment began)
(26)
Effect of daclizumab high-yield process in patients with highly active relapsing-remitting multiple sclerosis.
Giovannoni G, Radue E-W, Havrdova E, Riester K, Greenberg S, Mehta L, Elkins J
J Neurol. 2013 Dec 29. PMID: 24375015. Abstract
; a prospectively defined analysis showed that daclizumab HYP is associated with an increase in CD56(bright) natural killer cells, and that the numbers of such cells at weeks 4 and 8 correlate with the number of new or newly enlarging T2-hyperintense lesions in weeks 24 to 52, although treated individuals who displayed less expansion of these NK cells still exhibited fewer lesions than those on placebo
(37)
CD56(bright) natural killer cells and response to daclizumab HYP in relapsing-remitting MS.
Elkins J, Sheridan J, Amaravadi L, Riester K, Selmaj K, Bielekova B, Parr E, Giovannoni G
Neurol Neuroimmunol Neuroinflamm. 2015 Apr; 2(2):e65. Epub 2015 Jan 22. PMID: 25635261. Abstract
; posthoc analysis (of pooled results representing both doses) showed that daclizumab HYP decreased the development of new gadolinium-enhancing lesions to T1 hypointense lesions (black holes)
(46)
Daclizumab high-yield process reduced the evolution of new gadolinium-enhancing lesions to T1 black holes in patients with relapsing-remitting multiple sclerosis.
Radue E-W, Sprenger T, Vollmer T, Giovannoni G, Gold R, Havrdova E, Selmaj K, Stefoski D, You X, Elkins J
Eur J Neurol. 2016 Feb; 23(2):412-5. PMID: 26806217. Abstract
; daclizumab HYP (150 mg dose) had positive effects on health-related quality of life
(52)
Assessing the impact of multiple sclerosis disease activity and daclizumab HYP treatment on patient-reported outcomes: Results from the SELECT trial.
Phillips G, Guo S, Bender R, Havrdová E, Proskorovsky I, Vollmer T
Mult Scler Relat Disord. 2016 Mar; 6:66-72. Epub 2016 Feb 01. PMID: 27063626. Abstract
Trial name: 
Daclizumab in active, relapsing multiple sclerosis (CHOICE) trial (publ 2010; additional analysis publ 2013)
(8)
Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta.
Wynn D, Kaufman M, Montalban X, Vollmer T, Simon J, Elkins J, O'Neill G, Neyer L, Sheridan J, Wang C, et al.
Lancet Neurol. 2010 Apr; 9(4):381-90. Epub 2010 Feb 15. PMID: 20163990. Abstract
(23)
Daclizumab reduces CD25 levels on T cells through monocyte-mediated trogocytosis.
Zhang Y, McClellan M, Efros L, Shi D, Bielekova B, Tang M, Vexler V, Sheridan J
Mult Scler. 2013 Jul 11. PMID: 23846354. Abstract
Phase: 
Phase IIa trial
(8)
Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta.
Wynn D, Kaufman M, Montalban X, Vollmer T, Simon J, Elkins J, O'Neill G, Neyer L, Sheridan J, Wang C, et al.
Lancet Neurol. 2010 Apr; 9(4):381-90. Epub 2010 Feb 15. PMID: 20163990. Abstract
(23)
Daclizumab reduces CD25 levels on T cells through monocyte-mediated trogocytosis.
Zhang Y, McClellan M, Efros L, Shi D, Bielekova B, Tang M, Vexler V, Sheridan J
Mult Scler. 2013 Jul 11. PMID: 23846354. Abstract
Study Design: 
Company-sponsored randomized, placebo controlled, multinational, multicenter study to evaluate the efficacy of daclizumab [at either high (2 mg per kg every 2 weeks) or low (1 mg per kg every 4 weeks) dose] combined with interferon beta therapy on the number of new or enlarged gadolinium-enhancing lesions (primary endpoint)
(8)
Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta.
Wynn D, Kaufman M, Montalban X, Vollmer T, Simon J, Elkins J, O'Neill G, Neyer L, Sheridan J, Wang C, et al.
Lancet Neurol. 2010 Apr; 9(4):381-90. Epub 2010 Feb 15. PMID: 20163990. Abstract
Disease Stage: 
RRMS patients taking interferon beta
(8)
Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta.
Wynn D, Kaufman M, Montalban X, Vollmer T, Simon J, Elkins J, O'Neill G, Neyer L, Sheridan J, Wang C, et al.
Lancet Neurol. 2010 Apr; 9(4):381-90. Epub 2010 Feb 15. PMID: 20163990. Abstract
Enrollment/Number of Patients: 
230 patients enrolled; all completed the study
(8)
Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta.
Wynn D, Kaufman M, Montalban X, Vollmer T, Simon J, Elkins J, O'Neill G, Neyer L, Sheridan J, Wang C, et al.
Lancet Neurol. 2010 Apr; 9(4):381-90. Epub 2010 Feb 15. PMID: 20163990. Abstract
Duration: 
24 weeks
(8)
Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta.
Wynn D, Kaufman M, Montalban X, Vollmer T, Simon J, Elkins J, O'Neill G, Neyer L, Sheridan J, Wang C, et al.
Lancet Neurol. 2010 Apr; 9(4):381-90. Epub 2010 Feb 15. PMID: 20163990. Abstract
Status/Outcome: 
Both high and low doses of daclizumab, given with interferon beta, were associated with fewer gadolinium-enhancing lesions as compared to placebo and interferon beta
(8)
Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta.
Wynn D, Kaufman M, Montalban X, Vollmer T, Simon J, Elkins J, O'Neill G, Neyer L, Sheridan J, Wang C, et al.
Lancet Neurol. 2010 Apr; 9(4):381-90. Epub 2010 Feb 15. PMID: 20163990. Abstract
; longitudinal analysis showed a 30% reduction in the fraction of CD4+ T cells that were CD25+ two weeks after one dose of daclizumab (at either dose), which was not seen in the interferon beta therapy alone group
(23)
Daclizumab reduces CD25 levels on T cells through monocyte-mediated trogocytosis.
Zhang Y, McClellan M, Efros L, Shi D, Bielekova B, Tang M, Vexler V, Sheridan J
Mult Scler. 2013 Jul 11. PMID: 23846354. Abstract
Head-to-Head Trials: 
Trial name: 
Kappos et al., N. Engl. J. Med., October 2015 trial (DECIDE) (press releases, meeting reports, 2014, 2015; publ 2015)
(11)
Biogen Idec and Abbott Announce Enrollment of First Patient in Global Phase III Study of Daclizumab for Relapse Remitting Multiple Sclerosis
Abbot, 24 May 2010
Accessed on 3 Dec 2011 from http://www.abbott.com/news-media/press-releases/Press_Release_0863.htm.
(29)
Biogen Idec and AbbVie announce positive top-line results from Phase 3 study investigating daclizumab high-yield process in multiple sclerosis
Biogen Idec, 16 Jun 2014
Accessed on 19 Jun 2014 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2358&M=NewsV2&PID=61997.
(30)
Efficacy and Safety of Daclizumab High Yield Process Versus Interferon β 1a in Patients With Relapsing-Remitting Multiple Sclerosis ((DECIDE))
ClinicalTrials.gov, 12 Sep 2013
Accessed on 19 Jun 2014 from http://www.clinicaltrials.gov/ct2/show/NCT01064401.
(32)
Detailed results from Biogen Idec and AbbVie's pivotal Phase 3 DECIDE study further define the efficacy and safety profile of ZINBRYTA™ (daclizumab high-yield process)
Biogen Idec, 12 Sep 2014
Accessed on 15 Sep 2014 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2377&M=NewsV2&PID=61997.
(35)
Novel MS Drugs Advance
Gever J, MedPage Today, 4 Nov 2014
Accessed on 11 Nov 2014 from http://www.medpagetoday.com/Neurology/MultipleSclerosis/48404.
(45)
Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis.
Kappos L, Wiendl H, Selmaj K, Arnold DL, Havrdova E, Boyko A, Kaufman M, Rose J, Greenberg S, Sweetser M, et al.
N Engl J Med. 2015 Oct 8; 373(15):1418-28. PMID: 26444729. Abstract
Phase: 
Phase III trial
(11)
Biogen Idec and Abbott Announce Enrollment of First Patient in Global Phase III Study of Daclizumab for Relapse Remitting Multiple Sclerosis
Abbot, 24 May 2010
Accessed on 3 Dec 2011 from http://www.abbott.com/news-media/press-releases/Press_Release_0863.htm.
(29)
Biogen Idec and AbbVie announce positive top-line results from Phase 3 study investigating daclizumab high-yield process in multiple sclerosis
Biogen Idec, 16 Jun 2014
Accessed on 19 Jun 2014 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2358&M=NewsV2&PID=61997.
Study Design: 
Company-sponsored, multinational, double-blind, randomized, parallel-group, active-control trial to compare the efficacy of daclizumab high-yield process (HYP) (150 mg given subcutaneously once every 4 weeks) and intramuscular interferon beta-1a (30 microg given once every week); participants received daclizumab and an interferon beta-1a placebo or interferon beta-1a and a daclizumab placebo; the primary endpoint was the change in the annualized relapse rate (ARR) and the secondary endpoints were the number of new or newly enlarging T2-hyperintense lesions at week 96 and the risk of 3-month confirmed disability progression, measured by the Expanded Disability Status Scale (EDSS)
(11)
Biogen Idec and Abbott Announce Enrollment of First Patient in Global Phase III Study of Daclizumab for Relapse Remitting Multiple Sclerosis
Abbot, 24 May 2010
Accessed on 3 Dec 2011 from http://www.abbott.com/news-media/press-releases/Press_Release_0863.htm.
(29)
Biogen Idec and AbbVie announce positive top-line results from Phase 3 study investigating daclizumab high-yield process in multiple sclerosis
Biogen Idec, 16 Jun 2014
Accessed on 19 Jun 2014 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2358&M=NewsV2&PID=61997.
(30)
Efficacy and Safety of Daclizumab High Yield Process Versus Interferon β 1a in Patients With Relapsing-Remitting Multiple Sclerosis ((DECIDE))
ClinicalTrials.gov, 12 Sep 2013
Accessed on 19 Jun 2014 from http://www.clinicaltrials.gov/ct2/show/NCT01064401.
(45)
Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis.
Kappos L, Wiendl H, Selmaj K, Arnold DL, Havrdova E, Boyko A, Kaufman M, Rose J, Greenberg S, Sweetser M, et al.
N Engl J Med. 2015 Oct 8; 373(15):1418-28. PMID: 26444729. Abstract
Disease Stage: 
RRMS
(11)
Biogen Idec and Abbott Announce Enrollment of First Patient in Global Phase III Study of Daclizumab for Relapse Remitting Multiple Sclerosis
Abbot, 24 May 2010
Accessed on 3 Dec 2011 from http://www.abbott.com/news-media/press-releases/Press_Release_0863.htm.
Enrollment/Number of Patients: 
1841
(35)
Novel MS Drugs Advance
Gever J, MedPage Today, 4 Nov 2014
Accessed on 11 Nov 2014 from http://www.medpagetoday.com/Neurology/MultipleSclerosis/48404.
Duration: 
96 to 144 weeks
(11)
Biogen Idec and Abbott Announce Enrollment of First Patient in Global Phase III Study of Daclizumab for Relapse Remitting Multiple Sclerosis
Abbot, 24 May 2010
Accessed on 3 Dec 2011 from http://www.abbott.com/news-media/press-releases/Press_Release_0863.htm.
Status/Outcome: 
Daclizumab HYP was associated with a 45% reduction in the ARR [0.216 versus 0.393 for interferon beta-1a
(35)
Novel MS Drugs Advance
Gever J, MedPage Today, 4 Nov 2014
Accessed on 11 Nov 2014 from http://www.medpagetoday.com/Neurology/MultipleSclerosis/48404.
] and a 54% reduction in the number of new or newly enlarging T2-hyperintense lesions over 96 weeks [4.3 versus 9.4 for interferon beta-1a
(35)
Novel MS Drugs Advance
Gever J, MedPage Today, 4 Nov 2014
Accessed on 11 Nov 2014 from http://www.medpagetoday.com/Neurology/MultipleSclerosis/48404.
(45)
Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis.
Kappos L, Wiendl H, Selmaj K, Arnold DL, Havrdova E, Boyko A, Kaufman M, Rose J, Greenberg S, Sweetser M, et al.
N Engl J Med. 2015 Oct 8; 373(15):1418-28. PMID: 26444729. Abstract
]; differences in EDSS were not significant
(29)
Biogen Idec and AbbVie announce positive top-line results from Phase 3 study investigating daclizumab high-yield process in multiple sclerosis
Biogen Idec, 16 Jun 2014
Accessed on 19 Jun 2014 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2358&M=NewsV2&PID=61997.
; at week 96, 73% of participants on daclizumab HYP were relapse free versus 59% on interferon beta-1a
(32)
Detailed results from Biogen Idec and AbbVie's pivotal Phase 3 DECIDE study further define the efficacy and safety profile of ZINBRYTA™ (daclizumab high-yield process)
Biogen Idec, 12 Sep 2014
Accessed on 15 Sep 2014 from http://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2377&M=NewsV2&PID=61997.
; at week 144, 67% of participants on daclizumab HYP were relapse free versus 51% on interferon beta-1a
(35)
Novel MS Drugs Advance
Gever J, MedPage Today, 4 Nov 2014
Accessed on 11 Nov 2014 from http://www.medpagetoday.com/Neurology/MultipleSclerosis/48404.
; at week 144, the estimated incidence of disability progression confirmed at 12 weeks was not significantly different for the two drugs
(45)
Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis.
Kappos L, Wiendl H, Selmaj K, Arnold DL, Havrdova E, Boyko A, Kaufman M, Rose J, Greenberg S, Sweetser M, et al.
N Engl J Med. 2015 Oct 8; 373(15):1418-28. PMID: 26444729. Abstract
; serious adverse events occurred more frequently for those on daclizumab HYP (reported in 15% of participants) versus interferon beta-1a (10% of participants)
(45)
Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis.
Kappos L, Wiendl H, Selmaj K, Arnold DL, Havrdova E, Boyko A, Kaufman M, Rose J, Greenberg S, Sweetser M, et al.
N Engl J Med. 2015 Oct 8; 373(15):1418-28. PMID: 26444729. Abstract
; posthoc analysis showed that daclizumab-HYP was associated with more improvement in a composite of functional measures, including ambulation and cognition, than was interferon beta-1a
(42)
Novel MS Drug Offers Good Functional Outcomes
Fiore K, MedPage Today, 2 Jun 2015
Accessed on 9 Jun 2015 from http://www.medpagetoday.com/MeetingCoverage/CMSC/51896.
Other Trials: 
Trial name: 
Tramacere et al., Cochrane Database Syst. Rev., September 2015 study
(44)
Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.
Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G
Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract
Phase: 
Retrospective clinical trial analysis
(44)
Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.
Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G
Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract
Study Design: 
Retrospective network meta-analysis to compare the benefits of alemtuzumab, azathioprine, daclizumab, dimethyl fumarate, fingolimod, glatiramer acetate, immunoglobulins, interferon beta-1a (Avonex, Rebif), pegylated interferon beta-1a, interferon beta-1b, laquinimod, mitoxantrone, natalizumab, and teriflunomide; data were extracted from 39 randomized controlled trials that compared one or more of the 15 drugs used as monotherapy to placebo or another drug
(44)
Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.
Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G
Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract
Disease Stage: 
Adults with RRMS
(44)
Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.
Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G
Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract
Enrollment/Number of Patients: 
25,113 individuals were randomized in the studies included in the analyses
(44)
Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.
Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G
Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract
Duration: 
Median duration of studies, 24 months
(44)
Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.
Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G
Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract
Status/Outcome: 
Alemtuzumab was found to be the most protective against relapses during the first 24 months of therapy (moderate quality evidence); the next most protective were found to be mitoxantrone (very low quality evidence), natalizumab (high quality evidence), and fingolimod (moderate quality evidence); mitoxantrone (low quality evidence) was found to be the most effective at delaying disability worsening, followed by alemtuzumab (low quality evidence) and natalizumab (moderate quality evidence); these results must be interpreted conservatively because few trials have been performed for most of the drugs
(44)
Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.
Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G
Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract
Trial name: 
Liu et al., Cochrane Database Syst. Rev., December 2013 study
(25)
Daclizumab for relapsing remitting multiple sclerosis.
Liu J, Wang L-N, Zhan S, Xia Y
Cochrane Database Syst Rev. 2013; 12:CD008127. PMID: 24363032. Abstract
Phase: 
Retrospective clinical trial review
(25)
Daclizumab for relapsing remitting multiple sclerosis.
Liu J, Wang L-N, Zhan S, Xia Y
Cochrane Database Syst Rev. 2013; 12:CD008127. PMID: 24363032. Abstract
Study Design: 
Review of all randomized controlled clinical trials that evaluated the effects of daclizumab (alone or with another drug) versus placebo or other treatments
(25)
Daclizumab for relapsing remitting multiple sclerosis.
Liu J, Wang L-N, Zhan S, Xia Y
Cochrane Database Syst Rev. 2013; 12:CD008127. PMID: 24363032. Abstract
Disease Stage: 
RRMS
(25)
Daclizumab for relapsing remitting multiple sclerosis.
Liu J, Wang L-N, Zhan S, Xia Y
Cochrane Database Syst Rev. 2013; 12:CD008127. PMID: 24363032. Abstract
Enrollment/Number of Patients: 
851
(25)
Daclizumab for relapsing remitting multiple sclerosis.
Liu J, Wang L-N, Zhan S, Xia Y
Cochrane Database Syst Rev. 2013; 12:CD008127. PMID: 24363032. Abstract
Duration: 
N/A
(25)
Daclizumab for relapsing remitting multiple sclerosis.
Liu J, Wang L-N, Zhan S, Xia Y
Cochrane Database Syst Rev. 2013; 12:CD008127. PMID: 24363032. Abstract
Status/Outcome: 
Two trials were identified that met the criteria; too little evidence was available to assess if daclizumab had a greater effect than placebo on RRMS
(25)
Daclizumab for relapsing remitting multiple sclerosis.
Liu J, Wang L-N, Zhan S, Xia Y
Cochrane Database Syst Rev. 2013; 12:CD008127. PMID: 24363032. Abstract
Trial name: 
Borges et al., Mult. Scler. Relat. Disord., April 2013 study
(22)
The effect of daclizumab on brain atrophy in relapsing-remitting multiple sclerosis.
Borges IT, Shea CD, Ohayon J, Jones BC, Stone RD, Ostuni J, Shiee N, McFarland H, Bielekova B, Reich DS
Mult Scler Relat Disord. 2013 Apr 1; 2(2):133-140. PMID: 23580931. Abstract
Phase: 
Retrospective medical record review
(22)
The effect of daclizumab on brain atrophy in relapsing-remitting multiple sclerosis.
Borges IT, Shea CD, Ohayon J, Jones BC, Stone RD, Ostuni J, Shiee N, McFarland H, Bielekova B, Reich DS
Mult Scler Relat Disord. 2013 Apr 1; 2(2):133-140. PMID: 23580931. Abstract
Study Design: 
Analysis of MRI results (a total of 1332 scans from a single center) to determine whether daclizumab reduces the rate of brain atrophy
(22)
The effect of daclizumab on brain atrophy in relapsing-remitting multiple sclerosis.
Borges IT, Shea CD, Ohayon J, Jones BC, Stone RD, Ostuni J, Shiee N, McFarland H, Bielekova B, Reich DS
Mult Scler Relat Disord. 2013 Apr 1; 2(2):133-140. PMID: 23580931. Abstract
Disease Stage: 
RRMS
(22)
The effect of daclizumab on brain atrophy in relapsing-remitting multiple sclerosis.
Borges IT, Shea CD, Ohayon J, Jones BC, Stone RD, Ostuni J, Shiee N, McFarland H, Bielekova B, Reich DS
Mult Scler Relat Disord. 2013 Apr 1; 2(2):133-140. PMID: 23580931. Abstract
Enrollment/Number of Patients: 
70 MS cases; 26 were treated with daclizumab and 44 were not treated with this drug
(22)
The effect of daclizumab on brain atrophy in relapsing-remitting multiple sclerosis.
Borges IT, Shea CD, Ohayon J, Jones BC, Stone RD, Ostuni J, Shiee N, McFarland H, Bielekova B, Reich DS
Mult Scler Relat Disord. 2013 Apr 1; 2(2):133-140. PMID: 23580931. Abstract
Duration: 
4.3 years (median treatment time with daclizumab)
(22)
The effect of daclizumab on brain atrophy in relapsing-remitting multiple sclerosis.
Borges IT, Shea CD, Ohayon J, Jones BC, Stone RD, Ostuni J, Shiee N, McFarland H, Bielekova B, Reich DS
Mult Scler Relat Disord. 2013 Apr 1; 2(2):133-140. PMID: 23580931. Abstract
Status/Outcome: 
Daclizumab decreased the rate of brain atrophy relative to other disease-modifying therapies, probably because of a reduction in the atrophy rate of gray matter
(22)
The effect of daclizumab on brain atrophy in relapsing-remitting multiple sclerosis.
Borges IT, Shea CD, Ohayon J, Jones BC, Stone RD, Ostuni J, Shiee N, McFarland H, Bielekova B, Reich DS
Mult Scler Relat Disord. 2013 Apr 1; 2(2):133-140. PMID: 23580931. Abstract
Trial name: 
Safety and Efficacy Extension Study of Daclizumab High Yield Process (DAC HYP) to Treat Relapsing Remitting Multiple Sclerosis (SELECTION) (meeting report, October 2012; publ March 2014)
(18)
Safety issue puts daclizumab in doubt for MS
Medpage Today, 15 Oct 2012
Accessed on 1 Nov 2012 from http://www.medpagetoday.com/MeetingCoverage/ECTRIMS/35315.
(21)
Safety and efficacy extension study of daclizumab high yield process (DAC HYP) to treat relapsing remitting multiple sclerosis
ClinicalTrials.gov, 9 Aug 2012
Accessed on 26 Apr 2013 from http://clinicaltrials.gov/ct2/show/record/NCT01051349.
(28)
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECTION): a multicentre, randomised, double-blind extension trial.
Giovannoni G, Gold R, Selmaj K, Havrdova E, Montalban X, Radue E-W, Stefoski D, McNeill M, Amaravadi L, Sweetser M, et al.
Lancet Neurol. 2014 Mar 18. PMID: 24656609. Abstract
Phase: 
Extension of Phase IIb trial (SELECT)
(20)
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial.
Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue E-W, Stefoski D, Robinson R, Riester K, Rana J, et al.
Lancet. 2013 Apr 3. Epub 1969 Dec 31. PMID: 23562009. Abstract
(21)
Safety and efficacy extension study of daclizumab high yield process (DAC HYP) to treat relapsing remitting multiple sclerosis
ClinicalTrials.gov, 9 Aug 2012
Accessed on 26 Apr 2013 from http://clinicaltrials.gov/ct2/show/record/NCT01051349.
(28)
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECTION): a multicentre, randomised, double-blind extension trial.
Giovannoni G, Gold R, Selmaj K, Havrdova E, Montalban X, Radue E-W, Stefoski D, McNeill M, Amaravadi L, Sweetser M, et al.
Lancet Neurol. 2014 Mar 18. PMID: 24656609. Abstract
Study Design: 
Company-sponsored, multicenter, double-blind, open-label extension study to examine the safety and efficacy of continued treatment with daclizumab high-yield process (HYP), given subcutaneously every 4 weeks, such that patients originally given placebo were re-randomized to either the 150 mg or the 300 mg dose and patients originally given daclizumab HYP were re-randomized to either continue the same dose or to undergo a 20-week washout, after which the original dose was continued for 24 weeks; another primary aim was to monitor the long-term immunogenicity of the drug
(18)
Safety issue puts daclizumab in doubt for MS
Medpage Today, 15 Oct 2012
Accessed on 1 Nov 2012 from http://www.medpagetoday.com/MeetingCoverage/ECTRIMS/35315.
(21)
Safety and efficacy extension study of daclizumab high yield process (DAC HYP) to treat relapsing remitting multiple sclerosis
ClinicalTrials.gov, 9 Aug 2012
Accessed on 26 Apr 2013 from http://clinicaltrials.gov/ct2/show/record/NCT01051349.
(28)
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECTION): a multicentre, randomised, double-blind extension trial.
Giovannoni G, Gold R, Selmaj K, Havrdova E, Montalban X, Radue E-W, Stefoski D, McNeill M, Amaravadi L, Sweetser M, et al.
Lancet Neurol. 2014 Mar 18. PMID: 24656609. Abstract
Disease Stage: 
RRMS
(18)
Safety issue puts daclizumab in doubt for MS
Medpage Today, 15 Oct 2012
Accessed on 1 Nov 2012 from http://www.medpagetoday.com/MeetingCoverage/ECTRIMS/35315.
(28)
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECTION): a multicentre, randomised, double-blind extension trial.
Giovannoni G, Gold R, Selmaj K, Havrdova E, Montalban X, Radue E-W, Stefoski D, McNeill M, Amaravadi L, Sweetser M, et al.
Lancet Neurol. 2014 Mar 18. PMID: 24656609. Abstract
Enrollment/Number of Patients: 
517, with 92% participating for the full year
(18)
Safety issue puts daclizumab in doubt for MS
Medpage Today, 15 Oct 2012
Accessed on 1 Nov 2012 from http://www.medpagetoday.com/MeetingCoverage/ECTRIMS/35315.
(28)
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECTION): a multicentre, randomised, double-blind extension trial.
Giovannoni G, Gold R, Selmaj K, Havrdova E, Montalban X, Radue E-W, Stefoski D, McNeill M, Amaravadi L, Sweetser M, et al.
Lancet Neurol. 2014 Mar 18. PMID: 24656609. Abstract
Duration: 
52 weeks
(18)
Safety issue puts daclizumab in doubt for MS
Medpage Today, 15 Oct 2012
Accessed on 1 Nov 2012 from http://www.medpagetoday.com/MeetingCoverage/ECTRIMS/35315.
(28)
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECTION): a multicentre, randomised, double-blind extension trial.
Giovannoni G, Gold R, Selmaj K, Havrdova E, Montalban X, Radue E-W, Stefoski D, McNeill M, Amaravadi L, Sweetser M, et al.
Lancet Neurol. 2014 Mar 18. PMID: 24656609. Abstract
Status/Outcome: 
In patients who originally received placebo, the mean annualized relapse rate fell from 0.434 to 0.179 (59% reduction) after they switched to drug treatment and in patients who continuously received treatment, the reduced annualized relapse rates were maintained (meeting report, 15 October 2012)
(18)
Safety issue puts daclizumab in doubt for MS
Medpage Today, 15 Oct 2012
Accessed on 1 Nov 2012 from http://www.medpagetoday.com/MeetingCoverage/ECTRIMS/35315.
; 1 participant in the washout and re-initiation group at the 300 mg dose died of autoimmune hepatitis and the drug might have contributed to this condition; 7 participants exhibited neutralizing antidrug antibodies; overall, immunogenicity and adverse events were not higher in the second versus first year of continuous treatment or during washout and re-initiation of the drug
(28)
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECTION): a multicentre, randomised, double-blind extension trial.
Giovannoni G, Gold R, Selmaj K, Havrdova E, Montalban X, Radue E-W, Stefoski D, McNeill M, Amaravadi L, Sweetser M, et al.
Lancet Neurol. 2014 Mar 18. PMID: 24656609. Abstract
Trial name: 
Bielekova et al., Arch Neurol., April 2009 study
(9)
Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis.
Bielekova B, Howard T, Packer AN, Richert N, Blevins G, Ohayon J, Waldmann TA, McFarland HF, Martin R
Arch Neurol. 2009 Apr; 66(4):483-9. PMID: 19364933. Abstract
Phase: 
Phase II study
(9)
Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis.
Bielekova B, Howard T, Packer AN, Richert N, Blevins G, Ohayon J, Waldmann TA, McFarland HF, Martin R
Arch Neurol. 2009 Apr; 66(4):483-9. PMID: 19364933. Abstract
Study Design: 
Investigator-led, open-label, single-center study to determine whether daclizumab efficacy (measured as the reduction of contrast-enhancing lesions; primary endpoint) was dependent on combination with interferon beta or dose
(9)
Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis.
Bielekova B, Howard T, Packer AN, Richert N, Blevins G, Ohayon J, Waldmann TA, McFarland HF, Martin R
Arch Neurol. 2009 Apr; 66(4):483-9. PMID: 19364933. Abstract
Disease Stage: 
RRMS and SPMS
(9)
Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis.
Bielekova B, Howard T, Packer AN, Richert N, Blevins G, Ohayon J, Waldmann TA, McFarland HF, Martin R
Arch Neurol. 2009 Apr; 66(4):483-9. PMID: 19364933. Abstract
Enrollment/Number of Patients: 
12 RRMS and 3 SPMS patients enrolled; 13 completed the study
(9)
Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis.
Bielekova B, Howard T, Packer AN, Richert N, Blevins G, Ohayon J, Waldmann TA, McFarland HF, Martin R
Arch Neurol. 2009 Apr; 66(4):483-9. PMID: 19364933. Abstract
Duration: 
3 months interferon beta alone, 5.5 months interferon beta plus daclizumab, then 10 months daclizumab alone
(9)
Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis.
Bielekova B, Howard T, Packer AN, Richert N, Blevins G, Ohayon J, Waldmann TA, McFarland HF, Martin R
Arch Neurol. 2009 Apr; 66(4):483-9. PMID: 19364933. Abstract
Status/Outcome: 
Daclizumab monotherapy was associated with a stabilization of MRI disease activity in 9 of 13 patients, with four requiring additional interferon treatment
(9)
Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis.
Bielekova B, Howard T, Packer AN, Richert N, Blevins G, Ohayon J, Waldmann TA, McFarland HF, Martin R
Arch Neurol. 2009 Apr; 66(4):483-9. PMID: 19364933. Abstract
Trial name: 
Rose et al., Neurol., August 2007 study
(10)
Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results.
Rose JW, Burns JB, Bjorklund J, Klein J, Watt HE, Carlson NG
Neurology. 2007 Aug 21; 69(8):785-9. PMID: 17709711. Abstract
Phase: 
Phase II study
(10)
Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results.
Rose JW, Burns JB, Bjorklund J, Klein J, Watt HE, Carlson NG
Neurology. 2007 Aug 21; 69(8):785-9. PMID: 17709711. Abstract
Study Design: 
Investigator-led, open-label, single-center study to evaluate the effect of daclizumab on lesion size (primary endpoint)
(10)
Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results.
Rose JW, Burns JB, Bjorklund J, Klein J, Watt HE, Carlson NG
Neurology. 2007 Aug 21; 69(8):785-9. PMID: 17709711. Abstract
Disease Stage: 
RRMS patients treated with interferon but with continuing relapses
(10)
Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results.
Rose JW, Burns JB, Bjorklund J, Klein J, Watt HE, Carlson NG
Neurology. 2007 Aug 21; 69(8):785-9. PMID: 17709711. Abstract
Enrollment/Number of Patients: 
9 patients enrolled in and completed study
(10)
Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results.
Rose JW, Burns JB, Bjorklund J, Klein J, Watt HE, Carlson NG
Neurology. 2007 Aug 21; 69(8):785-9. PMID: 17709711. Abstract
Duration: 
27.5 months
(10)
Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results.
Rose JW, Burns JB, Bjorklund J, Klein J, Watt HE, Carlson NG
Neurology. 2007 Aug 21; 69(8):785-9. PMID: 17709711. Abstract
Status/Outcome: 
Drug was associated with a reduction in contrast enhancing lesions and improved clinical scores that were not controlled by interferon
(10)
Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results.
Rose JW, Burns JB, Bjorklund J, Klein J, Watt HE, Carlson NG
Neurology. 2007 Aug 21; 69(8):785-9. PMID: 17709711. Abstract
References
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.

Note: Compound name must be entered under "Substance Identification" and then "Names and Synonyms" selected to view synonyms.

FDA product review for daclizumab
Food and Drug Administration, 4 Dec 1997
Accessed on 3 Dec 2011 from http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/UCM272414.pdf.
Novel MS Drugs Advance
Gever J, MedPage Today, 4 Nov 2014
Accessed on 11 Nov 2014 from http://www.medpagetoday.com/Neurology/MultipleSclerosis/48404.
Biogen Idec Becomes Biogen
Biogen, 23 Mar 2015
Accessed on 7 Apr 2015 from http://biogen.newshq.businesswire.com/press-release/corporate/biogen-idec-becomes-biogen.
DOI: 
doi/10.7493/msdf.10.548.1