- Brand name: Zinbryta (Biogen Idec/AbbVie)
- Route of Administration: Subcutaneous injection (once per month)
- Type: Humanized monoclonal antibody
- Emerging treatment for: RRMS
- Status: Submitted to Health Canada for approval
Zinbryta (daclizumab high-yield process; DAC - HYP) is a newly patented version of the drug (formerly marketed as Zapanax by Hoffman-La Roche Ltd.)
How it Works
Daclizumab binds to CD25, an IL-2 receptor subunit on the surface of immune cells. This competitive antagonist prevents activation and growth of immune cells. Daclizumab also appears to increase the activity of CD56 (bright) natural killer cells which can regulate the immune system via lysis of T cells.
Research and Results
Daclizumab has previously been used to prevent kidney transplant rejection.
In a 2004 phase II study published by Bibiana Bielekova and colleagues, daclizumab was administered at 1mg/kg in addition to interferon beta. Results showed a 78% reduction in new lesions and a significant improvement in several clinical outcomes over 1.5 to 2 months of treatment. Further phase II studies revealed similar benefits.
CHOICE, a 24 week phase II trial examined the effect of introducing daclizumab treatment at a low or high dose to RRMS patients already taking interferon beta (participants were also followed for 48 weeks following treatment). Daclizumab treatment reduced the number of lesions (high dose and interferon beta reduced lesions by 72%; low dose and interferon beta reduced lesions by 25%) compared to treatment with interferon beta alone.
SELECT, a 52 week phase II trial published by Ralf Gold and team, examined the effect of placebo, 150mg or 300mg daclizumab treatment. Participants treated with daclizumab had lower relapse rates compared to placebo treated participants (150mg showed a 54% reduction; 300mg showed a 50% reduction), and more relapse free patients compared to the control group (150mg 81%; 300mg 80%).
Biogen Idec and AbbVie recently announced results of DECIDE, a phase III trial with more than 1800 participants from 28 countries. DECIDE focused on comparing a once monthly subcutaneous injection of daclizumab to a once weekly intramuscular injection of interferon beta-1a in RRMS patients. Participants administered daclizumab showed a 45% reduction in annualized relapse rate compared to participants administered interferon beta-1a. Additional results revealed a 54% reduction in the number of new or enlarging T2-hyperintese lesions relative to interferon beta-1a. The preliminary results reported by a press release were followed up by a detailed presentation of the results at the Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS) in September, 2014.
Adverse Effects Reported
Adverse effects reported include fatigue, headache, nausea, rash, musculoskeletal disorders, allergic reactions, infections, elevated liver enzymes, heart problems, and reduced platelet number. One death has been reported in a daclizumab treated participant resulting from psoas abscess (muscle abscess).
Bielekova B et al. Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon β. PNAS 2004; 101(23): 8705-8.
Rose JW et al. Treatment of multiple sclerosis with an anti-interleukin-2 receptor monoclonal antibody. Ann Neurol. 2004; 56(6):864–7.
Rose JW et al. Daclizumab phase II trial in relapsing and remitting multiple sclerosis: MRI and clinical results. Neurology. 2007;69(8):785–9.
Bielekova B et al. Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis. Arch Neurol. 2009; 66(4):483–9.
Bielekova B et al. Intrathecal effects of daclizumab treatment of multiple sclerosis. Neurology 2011; 77(21):1877–86.
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 Neurol. 2010; 9(4):381–90.
Gold R et al. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial. Lancet. 2013; 381: 2167-75.