Late Breaking News IISaturday, October 13, 2012, 09:15 - 09:30
Primary results of the SELECTION trial of daclizumab HYP in relapsing multiple sclerosisG. Giovannoni, R. Gold, K. Selmaj, E. Havrdova, X. Montalban, E.-W. Radue, D. Stefoski, M. McNeill, J. Rana, J. Elkins, G. OíNeill (London, GB; Bochum, DE; Lodz, PL; Prague, CZ; Barcelona, ES; Basel, CH; Chicago, US; Maidenhead, GB; Cambridge, US)
Background: The SELECTION trial was a 52-week, randomized, double-blind trial to evaluate the safety and efficacy of extended treatment with DAC HYP as well as a 24-week treatment interruption.
Methods: 517 (92%) of eligible subjects who completed treatment in the 52-week SELECT registrational trial entered the SELECTION trial. Subjects who had received placebo in SELECT (n=170) were randomized to receive monthly 150 mg or 300 mg SC DAC HYP. Subjects who had received DAC HYP in SELECT (n=347) were randomized to continue treatment at their current dose or to a 24-week treatment interruption (washout followed by treatment reinitiation at original dose). Since efficacy of the two DAC HYP dose groups were similar, results were combined for reporting.
Results: 92% (n=474) of randomized subjects completed the 52-week treatment phase of the study. Among patients who initiated treatment with DAC HYP in SELECTION, the 52-week ARR was reduced by 59% compared to the prior year (0.18 vs. 0.43; p<0.001) and the percent of subjects with confirmed 3-month disability progression was reduced by 50% compared to the prior year (5% vs. 10%; p =0.033). Among patients randomized to remain on continuous treatment with DAC HYP over 2 years, the ARR from year 1 was sustained during year 2 (0.148 vs. 0.165) while there were fewer new/newly enlarging T2 lesions in year 2 versus year 1 (1.2 vs. 1.85; p =0.032). After 2-years of DAC HYP therapy, 88% were free of confirmed disability progression. Among subjects randomized to treatment interruption, there was no evidence for disease rebound (mean Gd+ lesions at pre-treatment baseline vs. end of washout: 1.6 vs. 1.1). There was one death in the trial due to autoimmune hepatitis in the 300 mg treatment interruption group. The incidence of serious infections (2% vs. 2%) and serious cutaneous events (1% vs. 1%) was similar in SELECTION compared to SELECT while AST/ALT elevations >5x ULN were less common (1.5% vs. 4%). In subjects who remained on continuous treatment in the low-dose group (DAC HYP 150 mg), there were no AST/ALT elevations >5x ULN or serious cutaneous events during the second year of treatment.
Summary: These results support the efficacy findings of the SELECT trial and indicate that the efficacy of DAC HYP is sustained through the second year of therapy. Risks appeared similar compared to the first of year of treatment, and there was no evidence of rebound disease activity after a 24-week washout.
This study was supported by Biogen Idec and Abbott Biotherapeutics Corp.
G. Giovannoni has received research grant support from Bayer Schering Healthcare, Biogen Idec, GW Pharma, Merck Serono, Merz, Novartis, Teva, and Sanofi-Aventis and 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.
R. Gold has received speakersí honoraria or research grant support from Bayer Schering Healthcare, Biogen Idec, Merck Serono, Merz, Novartis, Teva, and Sanofi-Aventis and compensation for Advisory Board activities from Biogen Idec, Merck Serono, Novartis, and Teva.
K. Selmaj has received speakerís honoraria from Novartis, Merck Serono, Gedeon Richter, ONO Pharma, and Biogen Idec and personal compensation for participation in Advisory Boards and steering committees from Biogen Idec, Roche, Genzyme, ONO Pharma, Merck Serono, and Novartis.
E. Havrdova has received speakersí honoraria and research grant support from Bayer Schering Healthcare, Biogen Idec, Genzyme, Merck Serono, Novartis, and Teva and compensation for Advisory Board activities from Biogen Idec, Genzyme, Merck Serono, Novartis, and TEVA.
X. Montalban has received speaking honoraria and travel expenses for 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.
E.W. Radue has received research support and lecture fees from Actelion, Basilea, Bayer Schering, Biogen Idec, Merck Serono, Novartis, and others. Lecture fees have been mainly used for research funding at the Medical Image Analysis Center (formerly the MS MRI Evaluation Center), University Hospital Basel.
D. Stefoski has received research funding and support, and speaker bureau honoraria from Biogen Idec, EMD Serono, Teva, Pfizer, Elan, and Novartis.
M. McNeill, J. Rana, J. Elkins, and G. OíNeill are employees of Biogen Idec.