- Administered via intravenous infusion every four weeks; also studied when given in subcutaneous injections
- Daclizumab is being studied in both RRMS and secondary-progressive MS (SPMS)Daclizumab is a genetically engineered monoclonal antibody that binds to CD25, a receptor on T cells that is thought to become activated in response to MS. Daclizumab is believed to work by selectively targeting these activated T cells without causing general T-cell depletion. It is approved by the FDA for use in rheumatoid arthritis and other autoimmune diseases.Participants in the Phase II CHOICE study had either RRMS or SPMS, with worsening disease activity while taking one of the approved interferon therapies. The study showed that daclizumab was well tolerated when added to an interferon. A statistically-significant 72-percent reduction in the frequency of gadolinium-enhancing MRI lesions was seen in the high-dose group (300 mg every four weeks).
The Phase IIb SELECT trial, with 600 participants who have RRMS, reported successful outcomes in Fall 2011. SELECT was a one-year study of extended treatment with daclizumab, administered by subcutaneous injection. The study included three treatment arms, with two dose levels (at 150 mg and 300 mg) and a placebo group.
Results of the SELECT trial announced in August 2011 indicated that the annualized relapse rate was decreased by 54 percent in the 150-mg-dose group and by 50 percent in the 300-mg-dose group. It also met its secondary endpoints: the number of new gadolinium-enhancing lesions was reduced by 69 percent and 78 percent; the number of new or newly enlarging T2 hyperintense lesions was reduced by 70 percent and 79 percent; and the proportion of patients who relapsed was reduced by 50 percent and 51 percent; all for the low- and high-dose groups respectively. Sustained disability progression at one year was reduced by 57 percent with the lower dose and 43 percent with the higher dose.
Participants who completed this trial were enrolled in an extended trial called SELECTION to evaluate long-term safety and efficacy. One-year results of the SELECTION trial were presented22 at the ECTRIMS meeting in the fall of 2012. Patients who began treatment with daclizumab high yield process (DAC HYP) in the extension trial had a 59-percent reduction in annualized relapse rate compared to the year prior, while patients who continued on DAC HYP saw their low relapse rate from the prior year maintained. DAC HYP is administered subcutaneously once every four weeks, rather than via intravenous infusion every four weeks.
DAC HYP is being further studied in the DECIDE trial23, a Phase III study with 1,500 participants that will compare daclizumab DAC HYP to Avonex. DAC HYP will be administered subcutaneously once every four weeks for 96 to 144 weeks in a dose of 150 mg as compared to a weekly 30-mcg intramuscular injection of Avonex. The study began in March 2010, is fully enrolled, and is scheduled for completion in the spring of 2014. Outcome measures include relapse rate, functional decline and disability progression, as well as quality of life.
Daclizumab appears to be generally well-tolerated. Reported side effects in the Phase II studies include infections and abnormal liver function tests, diarrhea or constipation, and swelling of the extremities. One death in a daclizumab-treated patient was due to complications of a muscle abscess, and a second death was due to autoimmune liver inflammation. The safety profile of this medication will be closely followed in the ongoing Phase III trial.