Daclizumab Superior to IFN Beta in Phase III Multiple Sclerosis Trial
Relapse rate reduced
Positive results have been reported from the phase III DECIDE trial, which was designed to evaluate the superiority of once-monthly, subcutaneous daclizumab high-yield process (DAC HYP, Biogen Idec/Abbvie) compared with intramuscular interferon (IFN) beta-1a (Avonex, Biogen Idec) as a potential treatment for relapsing-remitting multiple sclerosis (RRMS), the most common form of MS.
The results showed that DAC HYP was superior on the study’s primary endpoint, demonstrating a statistically significant 45% reduction in the annualized relapse rate compared with IFN beta-1a (P < 0.0001).
DAC HYP also showed superiority on the first secondary endpoint (the number of new or newly enlarging T2-hyperintense lesions at week 96), with a 54% reduction compared with IFN beta-1a (P < 0.0001). On another secondary endpoint, DAC HYP reduced the risk of 3-month confirmed disability progression, as measured by the Expanded Disability Status Scale (EDSS), by 16% compared with IFN beta-1a, which was not statistically significant (P = 0.16). Using a pre-specified sensitivity analysis that accounted for 67 patients who did not have a confirmatory disability assessment, DAC HYP achieved a 21% reduction in the risk of sustained disability progression (P = 0.047).
The overall incidence of adverse events was comparable across the DAC HYP and IFN beta-1a treatment groups. In patients treated with DAC HYP compared with those treated with IFN beta-1a, there was an increased incidence of serious infections (4% vs. 2%, respectively), serious cutaneous reactions (2% vs. < 1%), and elevations of liver transaminases greater than five times the upper limit of normal (6% vs. 3%). Four deaths occurred in the IFN beta-1a group compared with one death in the DAC HYP group; none of these deaths was considered treatment-related.
The DECIDE trial was a 2- to 3-year global, randomized, double-blind study designed to determine whether DAC HYP would provide superior outcomes for certain clinical endpoints compared with treatment with IFN beta-1a. The study enrolled more than 1,800 subjects with RRMS in 28 countries. DECIDE was an active-comparator study with two treatment groups: 150 mg of subcutaneous DAC HYP administered every 4 weeks was compared with IFN beta-1a 30- mcg intramuscular injection administered once weekly.
After completing the DECIDE trial, subjects had the option to participate in an open-label extension study (EXTEND).
DAC HYP is a new form of humanized monoclonal antibody that binds to CD25, a receptor subunit expressed at high levels on T cells that become abnormally activated in MS. DAC HYP modulates interleukin-2 signaling without causing general immune-cell depletion. DAC HYP is believed to work by decreasing abnormally activated T cells and pro-inflammatory lymphoid-tissue inducer cells, and by increasing CD56bright natural killer cells — important cells that help regulate the immune system.
Source: Abbvie; June 16, 2014.