This study group reports the results of their 52-week, randomised, placebo-controlled, dose ranging, phase 2 study of daclizumab high-yield process (HYP) in RRMS.
Daclizumab is a humanised monoclonal antibody, which modulates interleukin-2 signalling by blocking the α subunit (CD25) on the interleukin-2 receptor, and is expressed mainly on the surface of activated and regulatory T cells, activated B cells and myeloid precursor cells. Genetic variation that results in increased expression of the α subunit (CD25) of the interleukin-2 receptor on naïve T cells heightens the risk for MS. Daclizumab HYP has the same aminoacid sequence as previous versions of daclizumab but differs in its glycosylation profile, resulting in decreased antibody-dependent cellular cytotoxicity activity.
The study included patients aged 18-55 years with RRMS and were randomly assigned (1:1:1) to subcutaneous injections of daclizumab HYP 150mg or 300mg, or placebo, every four weeks for 52 weeks. The primary endpoint was annualised relapse rate. 204 patients were assigned to receive placebo, 208 to daclizumab HYP 150mg and 209 to daclizumab HYP 300mg, of whom 92%, 94% and 94% respectively, completed follow-up to week 52.
The annualised relapse rate was lower for patients given daclizumab 150mg (54% reduction), or 300mg (50% reduction) than those given placebo. More patients were relapse free in the daclizumab HYP 150mg (81%) and 300mg (80%) groups than in the placebo group (64%). The safety data showed an increase in risk of infection and of cutaneous and hepatic events with a suspected immune-mediated cause. Subcutaneous daclizumab HYP given every four weeks led to clinically important effects on MS activity during one year of treatment. Longer and larger studies are needed to confirm the effect of daclizumab HYP on disability progression and to identify whether any effects are mediated by a reduction in relapse severity.
Authors: Gold R, Giovannoni G, Selmaj K
Source: Lancet. 2013 Apr 3. pii: S0140-6736(12)62190-4. doi: 10.1016/S0140-6736(12)62190-4. [Epub ahead of print]
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