- How does it work?
- How is it given?
- What are the results so far?
- Side effects
- What further studies are planned?
|Drug in development|
|What is it for?||Relapsing remitting multiple sclerosis (MS)|
- Daclizumab is a new drug treatment under investigation for relapsing remitting multiple sclerosis (MS). It is given as an injection under the skin once monthly.
- Daclizumab blocks the activity of interleukin 2, a chemical messenger in the immune system, and interferes with the growth of lymphocytes.
- In phase II studies, daclizumab reduced annual relapse rate by approximately 50% compared to placebo.
- In a phase II study, serious infections, serious skin reactions and impaired liver function occurred more frequently in people treated with daclizumab than in the placebo group.
How does it work?
Daclizumab is a monoclonal antibody which binds to CD25, a receptor on the surface of lymphocytes for interleukin 2, a chemical messenger in the immune system. This prevents activation and growth of lymphocytes which are involved in the immune attack in MS. Recent studies have shown that it increases the activity of natural killer cells, another immune system cell.
It has also been used to prevent kidney transplant rejection.
How is it given?
Daclizumab is given as an injection under the skin every 4 weeks.
What are the results so far?
A retrospective analysis of 55 people with relapsing remitting and secondary progressive MS who had received daclizumab reported that disability scores improved or stabilised in 60% and worsened in 40%. In other studies, daclizumab showed promise in treating people who had failed to respond to beta interferon or glatiramer acetate.
This study investigated the effects of combining interferon beta treatment with daclizumab in people with active relapsing MS. 230 people who had been on interferon beta for at least six months, were randomly allocated to one of three groups: high dose daclizumab, low dose daclizumab, or placebo, in addition to their standard interferon beta therapy. Daclizumab was given every two or four weeks over 24 weeks and participants were assessed for a further 48 weeks.
MRI scans before, after, and during treatment were used to monitor the appearance of new or larger active lesions.
The findings showed a 72% reduction in active lesions in the high dose daclizumab group and a 25% reduction in active lesions in the low dose daclizumab group compared to the placebo group. Daclizumab was generally well tolerated.
The SELECT phase II trial compared two doses of daclizumab and placebo in approximately 600 patients with relapsing remitting MS. Daclizumab, 150mg and 300mg, or placebo were taken as a subcutaneous (under the skin) injection every four weeks for 52 weeks.
Daclizumab reduced the annual relapse rate by 54% in the 150mg group and 50% in the 300mg group compared to the placebo group at one year.
Daclizumab also reduced the risk for sustained disability progression at 1 year by 57% in the 150-mg dose group. The rate was slightly lower in the 300-mg dose group, with a 43% reduction.
- In the SELECT study, serious infections, serious skin reactions and impaired liver function occurred more frequently in people treated with daclizumab than in the placebo group.
Results from the SELECTION extension study were reported at AAN 2013; among the 517 treated in SELECTION there were 13 cases of serious infections, 6 of serious skin reactions, 8 cases of impaired liver function and 3 cases of autoimmune reactions.
- There was 1 death in SELECT resulting from a complication of an abscess in a muscle of the lower back in a patient recovering from a serious skin reaction, and 1 in the SELECTION extension study, thought to be due to autoimmune hepatitis, where the body's own immune system attacks cells of the liver.
What further studies are planned?
Daclizumab compared to interferon beta 1a (Avonex) for relapsing remitting MS - DECIDE Trial
Extension study - SELECTION
DECIDE is a phase III study comparing daclizumab with interferon beta 1a (Avonex) in relapsing remitting MS (RRMS). Approximately 1,500 patients with RRMS in 28 countries are expected to be enrolled. All study participants will receive either an injection of daclizumab 150 mg administered under the skin once every four weeks and weekly injections of placebo, or weekly injections of interferon beta 1a and an injection of placebo once every four weeks.
The main measure of the trial is the effect of each treatment on relapse rate. The study will also examine the efficacy of daclizumab compared to interferon beta 1a in slowing functional decline and disability progression and in maintaining quality of life.
The DECIDE trial began recruiting in May 2010 and is due to finish in March 2014.
Further details of this study.
All participants in the SELECT trial were invited to continue treatment with daclizumab 150mg injected under the skin once a month to examine the long-term safety and effectiveness.
Estimated completion date May 2015
Further details of this study.
Rose JW, et al.
Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results.
Neurology 2007 69(8):785-789
Wynn D, et al.
Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta
Lancet Neurology 2010 Apr;9(4):381-90
Gold R, et al.
Daclizumab high-yield process (HYP) in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial.
Lancet 2013 Apr 3. [Epub ahead of print].