1. Daclizumab High-Yield Process in Relapsing-Remitting Multiple Sclerosis (SELECT): A Randomised, Double-blind, Placebo-controlled Trial
Aaron E. Miller, MD
Professor of Neurology and
Medical Director
The Corinne Goldsmith
Dickinson Center for
Multiple Sclerosis
Icahn School of Medicine at Mount Sinai
New York, NY
Gavin Giovannoni, MBBCh, PhD
Chair of Neurology
Blizard Institute
Barts and The London School of Medicine and Dentistry
London, UK

2. What Is Daclizumab High Yield Process (HYP)?
Daclizumab is a humanized monoclonal antibody
Blocks CD25 of the interleukin(IL)-2 receptor
Decreases IL-2 signalling at high-affinity receptor and increases signalling at intermediate-affinity receptor
Originally licensed for solid organ transplant rejection but withdrawn from market
But could it work in MS?
High yield process is a new way of processing the drug for a higher “cleaner” yield
Being evaluated for relapsing forms of MS

3. SELECT Trial—Design
Randomised, double-blind, placebo-controlled phase IIb trial
Part of a registration trial package
Three study arms: daclizumab HYP 150 mg (n = 208) or 300 mg (n = 209), or placebo (n = 204)
Subcutaneous every 4 weeks for 52 weeks
Primary endpoint:
Annualized relapse rate
Secondary endpoints:
New gadolinium-enhancing brain MRI lesions
New/newly enlarging T2 hyperintense lesions
Proportion relapse-free patients
Quality of life
Tertiary endpoint:
Confirmed disability progression, measured by EDSS change

4. SELECT Trial—Key Clinical and MRI Findings
Daclizumab
HYP 150 mg
HYP 300 mg
Placebo
Annualized relapse rate
0.21
(P<.0001)
0.23
(P = )
0.46
Proportion relapse-free
81%
80%
(P = .0003)
64%
New gadolinium-enhancing brain MRI lesions, weeks 8–24
69% 
78% 
New/newly enlarging T2 hyperintense lesions, week 52
70% 
79% 
3-month confirmed progression of disability
57% 
(P = .021)
43% 
(P = .091)
Gold R, et al. Lancet. 2013;381:

5. SELECT Trial—Safety and Tolerability
Well tolerated
Injection site reactions
Key adverse events of interest
Hypersensitivity reactions
Particularly skin reactions <1%
No Stevens-Johnson reactions
Serious infections, not opportunistic 1%–3%
Autoimmune hepatitis
Recognized by transaminitis
Gold R, et al. Lancet. 2013;381:

6. Daclizumab HYP—Next Steps
Phase III trial in relapsing-remitting MS (DECIDE)
Fully recruited and running
Interferon beta as active comparator
2 years
Results expected in 2016 or 2017
If phase III data show disability benefit relative to interferon, studies in progressive forms of MS should be considered
Future ideal candidate may be MS patients who are JC virus positive