Daclizumab High-Yield Process in Relapsing-Remitting Multiple Sclerosis

(SELECT): A Randomised, Double-blind, Placebo-controlled Trial

Aaron E. Miller, MDProfessor of Neurology and

Medical DirectorThe Corinne Goldsmith Dickinson Center for

Multiple SclerosisIcahn School of Medicine at

Mount SinaiNew York, NY

Gavin Giovannoni, MBBCh, PhDChair of Neurology

Blizard InstituteBarts and The London School of

Medicine and DentistryLondon, UK

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but withdrawn from market But could it work in MS?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

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

SELECT Trial—Key Clinical and MRI Findings

Daclizumab HYP 150 mg

Daclizumab HYP 300 mg

Placebo

Annualized relapse rate 0.21(P<.0001)

0.23(P = .00015)

0.46

Proportion relapse-free 81%(P<.0001)

80%(P = .0003)

64%

New gadolinium-enhancing brain MRI lesions, weeks 8–24

69% (P<.0001)

78% (P<.0001)

New/newly enlarging T2 hyperintense lesions, week 52

70% (P<.0001)

79% (P<.0001)

3-month confirmed progression of disability

57% (P = .021)

43% (P = .091)

Gold R, et al. Lancet. 2013;381:2167-2175.

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

SELECT Trial—Safety and Tolerability

Gold R, et al. Lancet. 2013;381:2167-2175.

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