5th Joint triennial congress of the European and Americas Committees
for Treatment and Research in Multiple Sclerosis
Amsterdam, The Netherlands

19.10.2011 - 22.10.2011
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Home - 22.10.2011 - Late breaking News


Late breaking News

Saturday, October 22, 2011, 08:45 - 09:00

A randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of daclizumab HYP monotherapy in relapsing-remitting multiple sclerosis: primary results of the SELECT trial

G. Giovannoni, R. Gold, K. Selmaj, E. Havrdova, X. Montalban, E.W. Radue, D. Stefoski, R. Robinson, K. Riester, J. Elkins, G. O'Neill (London, GB; Bochum, DE; Lodz, PL; Prague, CZ; Barcelona, ES; Basel, CH; Chicago, Redwood City, Cambridge, US)

Background: Daclizumab HYP (DAC HYP) is a humanized monoclonal antibody specific for the alpha subunit (CD25) of the human IL-2 receptor. DAC HYP modulates IL-2 signaling in-vivo and causes an expansion of CD56^bright natural killer cells.
Objective: To evaluate the safety and efficacy of DAC HYP monotherapy in patients with relapsing-remitting MS (RRMS).
Methods: We randomly assigned 600 patients with clinically definite RRMS and at least one MS relapse in the prior 12 months or one new Gd+ lesion in the prior 6 weeks to receive either DAC HYP 150 mg or DAC HYP 300 mg or placebo as a subcutaneous injection once every 4 weeks for 52 weeks. The primary endpoint was the annualized relapse rate (ARR).
Results: A total of 559 patients (93%) completed the treatment period. Among patients randomized to DAC HYP (150mg, 300mg) versus placebo, there was a significantly lower ARR (0.21, 0.23 vs. 0.46; p<0.001), a higher proportion of relapse free patients (81%, 80% vs. 64%; p<0.001); and a trend towards improvement in the MSIS-29 physical score (p<0.001, p=0.12 vs. placebo). There were significant reductions in the mean number of new or newly enlarging T2 lesions at 1-year (2.4, 1.7 vs. 8.1) and the mean number of new Gd+ lesions between weeks 8-24 in a monthly MRI substudy (n=309) (1.5, 1.0 vs. 4.8) in the DAC HYP 150mg and 300mg groups vs. placebo (p<0.001 for all comparisons). The risk of 3-month sustained disability progression at 1-year, a tertiary study endpoint, was reduced by 57% (p=0.02) in the DAC HYP 150mg group and by 43% (p=0.09) in the DAC HYP 300mg group. Serious adverse events, excluding MS relapses, occurred in 5% in the placebo group, 6% in the DAC HYP 150mg group, and 8% in the DAC HYP 300mg group. One DAC HYP treated patient who was recovering from a serious rash died due to a complication of a psoas abscess. Serious adverse events in DAC HYP treated patients, included an increase in serious infections (2%), serious cutaneous events (1%) and elevations in liver function tests (ALT/AST) >5x ULN (4%).
Conclusions: Monthly, subcutaneous DAC HYP monotherapy demonstrated a robust and clinically meaningful effect on MS activity, including evidence for early impact on disability progression. These benefits and risks warrant further evaluation.

Ralf Gold disclosure: I have received speakers' honoraria and research grant support from Bayer Schering Healthcare, Biogen Idec, Merck Serono, Merz, Novartis, Teva and sanofi-aventis. Also I have received compensation for Advisory Board activities from Biogen Idec, Merck Serono, Novartis and TEVA. Gavin Giovannoni disclosure: I have received research grant support from Bayer Schering Healthcare, Biogen Idec, GW Pharma, Merck Serono, Merz, Novartis, Teva and sanofi-aventis. I have received personal compensation for participating on Advisory Boards in relation to clinical trial design, trial steering committees and data and safety monitoring committees from: Bayer Schering Healthcare, Biogen Idec, Eisai, Elan, Five Prime Therapeutics, Genzyme, Genentech, GSK, Ironwood Pharma, Merck Serono, Novartis, Pfizer, Roche, sanofi-aventis, Synthon BV, Teva, UCB Pharma and Vertex Pharmaceuticals. Eva Havrdova disclosure: I have received speakers' honoraria and research grant support from Bayer Schering Healthcare, Biogen Idec, Genzyme, Merck Serono, Novartis, and Teva. Also I have received compensation for Advisory Board activities from Biogen Idec, Genzyme, Merck Serono, Novartis and TEVA. Xavier Montalban disclosure: Dr. Montalban has received speaking honoraria and travel expenses for speaking and scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Bayer Schering Pharma, Biogen Idec, EMD Merck Serono, Genentech, Genzyme, Novartis, sanofi-aventis, Teva Pharmaceuticals, Almirall and BTG. Ernst Radue disclosure: I have received research support (mainly for MS projects) and lecture fees from: Actelion, Basilea, Bayer Schering, Biogen Idec, Merck Serono, Novartis and others. Lecture fees have have been mainly used for research funding at the Medical Image Analysis Center (former MS MRI Evaluation Center), University Hospital Basel Krzysztof Selmaj disclosure: I have received speaker's honoraria from Novartis, Merck Serono, Gedeon Richter, ONO Pharma, and Biogen Idec. I also received personal compensation for participation in advisory boards and steering committees from Biogen Idec, Roche, Genzyme, ONO Pharma, Merck Serono, and Novartis. Dusan Sefoski disclosure: I have received research funding and support, and speaker bureau honoraria from: Biogen Idec, EMD Serono, Teva, Pfizer, Elan, and Novartis. Randy Robinson disclosure: Dr. Robinson is a full-time employee of Abbott Biotherapeutics. Jacob Elkins disclosure: Dr. Elkins is a full-time employee of Biogen Idec. Katherine Riester: Ms. Riester is a full-time employee of Biogen Idec. Gilmore O'Neill disclosure: Dr. O'Neill is a full-time employee of Biogen Idec. This study was supported by Biogen Idec and Abbott Biotherapeutics Corp. Editorial assistance was provided by Alison Gagnon of UBC Scientific Solutions, which was supported by Biogen Idec.