Late Breaking News II
Saturday, October 13, 2012, 09:15 – 09:30
G. Giovannoni, R. Gold, K. Selmaj, E. Havrdova, X. Montalban, E.-W. Radue, D. Stefoski, M. McNeill, J. Rana, J. Elkins, G. O’Neill (London, UK; Bochum, DE; Lodz, PL; Prague, CZ; Barcelona, ES; Basel, CH; Chicago, US; Maidenhead, UK; 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.
“These results are very interesting. Daclizumab seems to be having an impact on disability beyond what you expect from its impact on relapses. Could Daclizumab be targeting a process responsible for the degenerative component of MS? We will need to wait and see; a large phase 3 trial is currently underway to answer this question. Why doesn’t Biogen-Idec/Abbott do a trial in progressive MS to answer this question? I have asked them this. I think they should do it sooner than later; progressive MSers deserve it!”