OBJECTIVE: SELECTED, an open-label extension study, evaluated daclizumab beta treatment for up to 6 years in participants with relapsing multiple sclerosis who completed the randomized SELECT/SELECTION studies. We report final results of SELECTED. METHODS: Eligible participants who completed 1-2 years of daclizumab beta treatment in SELECT/SELECTION received daclizumab beta 150 mg subcutaneously every 4 weeks for up to 6 years in SELECTED. Safety assessments were evaluated for the SELECTED treatment period; efficacy data were evaluated from first dose of daclizumab beta in SELECT/SELECTION. RESULTS: Ninety percent (410/455) of participants who completed treatment in SELECTION enrolled in SELECTED. Within SELECTED, 69% of participants received daclizumab beta for > 3 years, 39% for > 4 years, and 9% for > 5 years; 87% of participants experienced an adverse event and 26% a serious adverse event (excluding multiple sclerosis relapse). No deaths occurred. Overall, hepatic events were reported in 25% of participants; serious hepatic events in 2%. There were no confirmed cases of immune-mediated encephalitis. Based on weeks from the first daclizumab beta dose in SELECT/SELECTION, adjusted annualized relapse rate (95% confidence interval) for weeks 0-24 was 0.21 (0.16-0.29) and remained low on continued treatment. Overall incidence of 24-week confirmed disability progression was 17.4%. Mean numbers of new/newly enlarging T2 hyperintense lesions remained low; percentage change in whole brain volume decreased over time. CONCLUSIONS: The effects of daclizumab beta on clinical and radiologic outcomes were sustained for up to ~ 8 years of treatment. No new safety concerns were identified in SELECTED. TRIAL REGISTRATION: Clinicaltrials.gov NCT01051349; first registered on January 15, 2010.

AbbVie Inc Redwood City CA USA

Barts and The London School of Medicine and Dentistry Queen Mary University of London London UK

Biogen Cambridge MA USA

Biogen Maidenhead UK

Department of Neurology 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Neurology University of Warmia and Mazury Olsztyn Poland

DKD Helios Klinik Wiesbaden Wiesbaden Germany

Hospital Vall d'Hebron University Barcelona Spain

Medical Image Analysis Center University Hospital Basel Basel Switzerland

Rush University Medical Center Chicago IL USA

St Josef Hospital Ruhr University Bochum 44791 Bochum Germany

Zobrazit více v PubMed

Biogen (2018) Biogen and Abbvie announce the voluntary worldwide withdrawal of marketing authorizations for Zinbryta

Cohan S. Therapeutic efficacy of monthly subcutaneous injection of daclizumab in relapsing multiple sclerosis. Biol Targets Ther. 2016;10:119–138. PubMed PMC

Comi G, O'Connor P, Montalban X, Antel J, Radue EW, Karlsson G, Pohlmann H, Aradhye S, Kappos L. Phase II study of oral fingolimod (FTY720) in multiple sclerosis: 3-year results. Mult Scler. 2010;16:197–207. PubMed

Confavreux C, Vukusic S. The clinical course of multiple sclerosis. Handb Clin Neurol. 2014;122:343–369. PubMed

De Stefano N, Stromillo ML, Giorgio A, Bartolozzi ML, Battaglini M, Baldini M, Portaccio E, Amato MP, Sormani MP. Establishing pathological cut-offs of brain atrophy rates in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2016;87:93–99. PubMed PMC

European Medicines Agency (2017) EMA concludes review of Zinbryta and confirms further restrictions to reduce risk of liver damage. https://www.ema.europa.eu/documents/referral/zinbryta-article-20-referral-ema-concludes-review-zinbryta-confirms-further-restrictions-reduce-risk_en.pdf. Accessed 11 Oct 2019

European Medicines Agency (2018) EMA recommends immediate suspension and recall of multiple sclerosis medicine Zinbryta. http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2018/03/WC500245167.pdf. Accessed 11 Oct 2019

European Medicines Agency (2018) EMA urgently reviewing multiple sclerosis medicine Zinbryta following cases of inflammatory brain disorders. http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2018/03/WC500244890.pdf. Accessed 11 Oct 2019

European Medicines Agency (2018) Zinbryta (daclizumab). https://www.ema.europa.eu/en/medicines/human/EPAR/zinbryta. Accessed 11 Oct 2019

Faissner S, Gold R. Efficacy and safety of the newer multiple sclerosis drugs approved since 2010. CNS Drugs. 2018;32:269–287. PubMed

Giovannoni G, Butzkueven H, Dhib-Jalbut S, Hobart J, Kobelt G, Pepper G, Sormani MP, Thalheim C, Traboulsee A, Vollmer T. Brain health: time matters in multiple sclerosis. Mult Scler Relat Disord. 2016;9(Suppl 1):S5–S48. PubMed

Giovannoni G, Gold R, Selmaj K, Havrdova E, Montalban X, Radue EW, Stefoski D, McNeill M, Amaravadi L, Sweetser M, Elkins J, O'Neill G. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECTION): a multicentre, randomised, double-blind extension trial. Lancet Neurol. 2014;13:472–481. PubMed

Giovannoni G, Kappos L, Gold R, Khatri BO, Selmaj K, Umans K, Greenberg SJ, Sweetser M, Elkins J, McCroskery P. Safety and tolerability profile of daclizumab in patients with relapsing-remitting multiple sclerosis: an integrated analysis of clinical studies. Mult Scler Relat Disord. 2016;9:36–46. PubMed

Gold R, Arnold DL, Bar-Or A, Hutchinson M, Kappos L, Havrdova E, MacManus DG, Yousry TA, Pozzilli C, Selmaj K, Sweetser MT, Zhang R, Yang M, Potts J, Novas M, Miller DH, Kurukulasuriya NC, Fox RJ, Phillips TJ. Long-term effects of delayed-release dimethyl fumarate in multiple sclerosis: Interim analysis of ENDORSE, a randomized extension study. Mult Scler. 2017;23:253–265. PubMed PMC

Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue EW, Stefoski D, Robinson R, Riester K, Rana J, Elkins J, O'Neill G. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial. Lancet. 2013;381:2167–2175. PubMed

Gold R, Radue EW, Giovannoni G, Selmaj K, Havrdova E, Stefoski D, Sprenger T, Montalban X, Cohan S, Umans K, Greenberg SJ, Ozen G, Elkins J. Safety and efficacy of daclizumab in relapsing-remitting multiple sclerosis: 3-year results from the SELECTED open-label extension study. BMC Neurol. 2016;16:117. PubMed PMC

Goodman AD, Bethoux F, Brown TR, Schapiro RT, Cohen R, Marinucci LN, Henney HR, 3rd, Blight AR. Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: results of open-label extensions of two phase 3 clinical trials. Mult Scler. 2015;21:1322–1331. PubMed PMC

Hart FM, Bainbridge J. Current and emerging treatment of multiple sclerosis. Am J Manag Care. 2016;22:S159–S170. PubMed

ICH Expert Working Group (1996) Guideline for good clinical practice E6(R1) ICH harmonised tripartite guideline. www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_Guideline.pdf. Accessed 4 Feb 2019

Kappos L, O'Connor P, Radue EW, Polman C, Hohlfeld R, Selmaj K, Ritter S, Schlosshauer R, von Rosenstiel P, Zhang-Auberson L, Francis G. Long-term effects of fingolimod in multiple sclerosis: the randomized FREEDOMS extension trial. Neurology. 2015;84:1582–1591. PubMed PMC

Kappos L, Wiendl H, Selmaj K, Arnold DL, Havrdova E, Boyko A, Kaufman M, Rose J, Greenberg S, Sweetser M, Riester K, O'Neill G, Elkins J. Daclizumab HYP versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2015;373:1418–1428. PubMed

Krueger JG, Kircik L, Hougeir F, Friedman A, You X, Lucas N, Greenberg SJ, Sweetser M, Castro-Borrero W, McCroskery P, Elkins J. Cutaneous adverse events in the randomized, double-blind, active-comparator DECIDE study of daclizumab high-yield process versus intramuscular interferon beta-1a in relapsing-remitting multiple sclerosis. Adv Ther. 2016;33:1231–1245. PubMed PMC

Lima G, McCroskery P, Dewar R, Castillo JJ, Holman J, Umans K, Fam S. Characterisation of the lymphadenopathy events observed in the daclizumab HYP clinical trials. Mult Scler. 2016;22:297.

Minocha M, Tran JQ, Sheridan JP, Othman AA. Blockade of the high-affinity interleukin-2 receptors with daclizumab high-yield process: pharmacokinetic/pharmacodynamic analysis of single- and multiple-dose phase I trials. Clin Pharmacokinet. 2016;55:121–130. PubMed

Oh J, Saidha S, Cortese I, Ohayon J, Bielekova B, Calabresi PA, Newsome SD. Daclizumab-induced adverse events in multiple organ systems in multiple sclerosis. Neurology. 2014;82:984–988. PubMed PMC

Sheridan JP, Zhang Y, Riester K, Tang MT, Efros L, Shi J, Harris J, Vexler V, Elkins JS. Intermediate-affinity interleukin-2 receptor expression predicts CD56bright natural killer cell expansion after daclizumab treatment in the CHOICE study of patients with multiple sclerosis. Mult Scler. 2011;17:1441–1448. PubMed

Stork L, Brück W, von Gottberg P, Pulkowski U, Kirsten F, Glatzel M, Rauer S, Scheibe F, Radbruch H, Hammer E, Stürner KH, Kaulen B, Heesen C, Hoffmann F, Brock S, Pawlitzki M, Bopp T, Metz I. Severe meningo-/encephalitis after daclizumab therapy for multiple sclerosis. Mult Scler. 2019;25:1618–1632. PubMed

Lancet T. End of the road for daclizumab in multiple sclerosis. Lancet. 2018;391:1000. PubMed

US Food & Drug Administration (2016) FDA approves Zinbryta to treat multiple sclerosis. https://www.fda.gov/news-events/press-announcements/fda-approves-zinbryta-treat-multiple-sclerosis. Accessed 10 Oct 2019

Zhang Y, McClellan M, Efros L, Shi D, Bielekova B, Tang MT, Vexler V, Sheridan JP. Daclizumab reduces CD25 levels on T cells through monocyte-mediated trogocytosis. Mult Scler. 2014;20:156–164. PubMed PMC

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NCT01051349