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.
"These results are very interesting and surprising. Firstly, DAC works in an interesting way by targeting a messenger in the immune system called IL2, it blocks in binding to its high affinity receptor. Secondly, DAC had an impact on disability in a 52 week study; this is very unusual finding in a one year study that is traditionally too short to see an impact on disability. The latter suggests DAC may be a very effective therapy in relapsing MS."