Efficacy and safety of siponimod in secondary Efficacy and safety of siponimod in secondary progressive multiple sclerosis - Results of the progressive multiple sclerosis - Results of the Disclosures Disclosures placebo controlled, double-blind, Phase III placebo controlled, double-blind, Phase III EXPAND study EXPAND study � In the past 12 months, Bruce Cree has � In the past 12 months, Bruce Cree has received personal compensation for received personal compensation for consulting from Abbvie, Biogen, EMD consulting from Abbvie, Biogen, EMD Bruce Cree on behalf of the EXPAND Study Serono, Novartis, and Shire. Serono, Novartis, and Shire. Steering Committee and Investigators EXPAND: A randomised, double-blind, EXPAND: A randomised, double-blind, Siponimod Siponimod placebo controlled, event- and exposure- placebo controlled, event- and exposure- A selective S1P receptor modulator A selective S1P receptor modulator driven study driven study Novel, selective S1P 1 and S1P 5 receptor modulator Novel, selective S1P 1 and S1P 5 receptor modulator � � � inhibits the egress of lymphocytes from lymph nodes 1 � inhibits the egress of lymphocytes from lymph nodes 1 � Randomization 2:1 siponimod: placebo � Randomization 2:1 siponimod: placebo Readily crosses BBB and may have effects within the CNS 2,3 Readily crosses BBB and may have effects within the CNS 2,3 � Event driven study design: 374 confirmed disability � Event driven study design: 374 confirmed disability � � progression events were needed progression events were needed Half-life ~30 hours; washout period of 6 days 1 allows for fast immune Half-life ~30 hours; washout period of 6 days 1 allows for fast immune � � reconstitution reconstitution � Duration of exposure to study drug was variable � Duration of exposure to study drug was variable Phase 2 BOLD study (RRMS): a dose of Phase 2 BOLD study (RRMS): a dose of � � � Patients with 6-month CDP had option to switch to open- � Patients with 6-month CDP had option to switch to open- 2 mg/day achieved near-maximal efficacy and dose titration mitigated first 2 mg/day achieved near-maximal efficacy and dose titration mitigated first label siponimod or other DMTs label siponimod or other DMTs dose bradycardia 4 dose bradycardia 4 BBB: blood-brain barrier; BOLD: BAF312 (siponimod) on MRI Lesion given once-Daily; CNS: central nervous system; RRMS: relapsing-remitting multiple sclerosis; S1P: sphingosine 1-phosphate 1. Gergely P, et al. Br J Pharmacol. 2012;167:1035-1047. 2. Seabrook TJ, et al. Mult Scler. 2010;16:S301. Abstract P858. 3. Brinkmann V. Br J Pharmacol. 2009;158:1173. 4. Selmaj K, et al. Lancet Neurol. 2013; 12(8): 756-767. 3 Kappos L et al. ECTRIMS 2016 1
Primary and secondary Primary and secondary Key inclusion and exclusion Key inclusion and exclusion endpoints endpoints criteria criteria Primary endpoint Key inclusion criteria • Time to 3-month Confirmed Disease Progression (CDP), assessed by EDSS* 1 Efficacy is reported as a hazard ratio, which quantifies risk reduction • Age: 18–60 years old under siponimod treatment relative to placebo • Prior history of relapsing-remitting MS • Secondary progressive course of MS (SPMS), defined by a progressive Secondary endpoints increase in disability (of at least 6 months duration) in the absence of relapses or independent of relapses • Key secondary endpoints • EDSS score of 3.0–6.5 ─ Time to 3-month confirmed worsening of at least 20% from • Evidence for EDSS progression in the 2 years prior to study of 1 point or baseline in the Timed 25-foot walk test (T25FW) more in patients with a screening EDSS score of less than 6.0 ─ Change from baseline in T2 lesion volume ─ ≥ 0.5 points for patients with EDSS ≥ 6.0 at screening • Other secondary endpoints ─ 6-month CDP, assessed by EDSS* 1 ─ Annualised relapse rate Key exclusion criteria ─ Change from baseline in brain volume ─ others ( analysis ongoing) • Safety and tolerability • Standard exclusion criteria • Defined washout periods or exclusion criteria for other MS medications 5 6 Kappos L et al. ECTRIMS 2016 Kappos L et al. ECTRIMS 2016 Demographics and baseline Demographics and baseline characteristics characteristics Patient Disposition Patient Disposition Siponimod Placebo N=1105 N=546 Age, years 48.0 (7.8) 48.1 (7.9) Age, n (%) � 1651 subjects randomized � 1651 subjects randomized 18-40 188 (17.0) 103 (18.9) >41 917 (83.0) 443 (81.1) � 1100 siponimod � 1100 siponimod Duration of MS since first symptom, years 17.12 (8.39) 16.23 (8.23) Time since conversion to SPMS, years 3.85 (3.61) 3.56 (3.28) � 82% completed double blind period � 82% completed double blind period EDSS � 546 placebo � 546 placebo Mean (SD) 5.43 (1.08) 5.41 (1.03) Median (Min-Max) 6.0 (2.0-7.0) 6.0 (2.5-7.0) � 78% completed double blind period � 78% completed double blind period Number of relapses in last 2 years prior to screening, n (%)* 0 712 (64.4) 343 (62.8) � Actual median time in double blind period was 18 � Actual median time in double blind period was 18 ≥ 1 390 (35.3) 202 (37.0) months months Number of Gd+ T1 lesions, n (%)* 0 833 (75.4) 415 (76.0) � Actual total double blind study duration was 37 � Actual total double blind study duration was 37 ≥ 1 237 (21.4) 114 (20.9) All randomised set. Data represented as mean (SD), unless otherwise specified months months *Number and percentage of patients with missing screening or baseline observations not displayed 8 Kappos L et al. ECTRIMS 2016 2
Recommend
More recommend
