Zenapax® (daclizumab)

Parent companies: Biogen Idec, Inc and Abbott Laboratories

• Administered via intravenous infusion every four weeks; also studied when given in subcutaneous injections.
  
  
• Zenapax 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 Zenapax was well tolerated when added to an interferon. A 25-percent reduction was seen in the frequency of gadolinium-enhancing lesions in the low-dose group (150 mg every four weeks), and a 72-percent reduction was seen in the high-dose group (300 mg every four weeks).
  
  
• The ongoing Phase IIb SELECT trial, with 600 participants who have RRMS, is scheduled for completion in September 2015. It is a one-year study that will be assessing the safety and immunogenicity (the incidence of the development of antibodies) of extended treatment with daclizumab, administered by subcutaneous injection. The study includes three treatment arms, with two dose levels (at 150 mg and 300 mg) and a placebo group. Participants who complete this trial will be enrolled in an extended trial that will evaluate long-term safety and efficacy.
  
  
• Preliminary 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. Additional analyses are ongoing.
  
  
• A Phase III study with 1,500 participants will compare Daclizumab High Yield Process (DAC HYP) to Avonex. DAC HYP is 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 is currently recruiting patients; it began in March 2010 and is scheduled for completion in January 2014. Outcome measures include relapse rate, functional decline and disability progression, and quality of life.
  
  
• Daclizumab appears to be well-tolerated. Reported side effects include infections and abnormal liver function tests, diarrhea or constipation, and swelling of the extremities (bloating).