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Post Hoc Analysis of Efficacy of Cladribine Tablets In DXT49 Post hoc Analysis of Efficacy of Cladribine Tablets in Patients with Relapsing- RESULTS (cont.) Remitting Multiple Sclerosis Aged Over and Under 30 Years in the CLARITY Study Cladribine Tablets Improved MRI Outcomes in Both Age Groups over 96 Weeks vs. Placebo M.S. Freedman,1 G. Pardo,2 N. De Stefano,3 J. Aldridge,4 S. Syed,4 Y. Hyvert,5 A. Galazka,6 C. Lemieux,7 G. Giovannoni8 Cumulative new T1 Gd+ lesions Mean Cumulative active T2 lesions Mean 1 2 3 GET POSTER PDF University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada; Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; University of Siena, Siena, Italy; Copies of this poster obtained ≤30 years ≤30 years 4 5 6 through QR (Quick Response) code EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany; Merck KGaA, Darmstadt, Germany; Merck, Aubonne, Switzerland, an are for personal use only and may 7 8 not be reproduced without written affiliate of Merck KGaA, Darmstadt, Germany; EMD Inc., Mississauga, ON, Canada, an affiliate of Merck KGaA, Darmstadt, Germany; Queen Mary University of London, Blizard Institute, Barts and permission of the authors. The London School of Medicine and Dentistry . vs 0.6 .9 vs 1.9 CONCLUSIONS 0 years 0 years 2.0 vs 0.1 .0 vs 0.6 In both age subgroups (≤30 or >30 years of age), treatment with cladribine 2.9 tablets . mgkg resulted in similar efficacy outcomes. While the proportion 66 53% 0. in patients ≤30 years patients NEDA of patients with NEDA was higher in those treated with cladribine tablets ARR 1. Placebo Cladribine tablets 3.5 mg/kg ≤30 years >30 years . mgkg vs. placebo, the difference was greater ≤30 years group . in patients >30 years Cladribine Tablets Increased the Probability of Being Free of 3-month Confirmed EDSS Progression in Both Age Groups BACKGROUND METHODS (cont.) ≤30 years 0 years ● Efficacy of cladribine tablets has been demonstrated in patients with RRMS in the 96-week Patients CLARITY study1 ≤30 years 0 years 1.0 1.0 ● Prior post hoc analyses of CLARITY found that cladribine tablets 3.5 mg/kg treatment resulted 12 8% in similar benefits across the age spectrums (≤40 years/>40 years) of the studied patients in Mean age (SD) 2.6 (.) years 2. (.) years 2. (.) years 2. (.) years risk reduction of relapse and odds of remaining free from disease activity2,3 Male 1.2 .6 1.9 29.0 0.9 0.9 Mean disease duration .0 (.1) years 2. (2.) years . (.) years . (6.0) years from first onset (SD) Previous therapy 0.8 0.8 2. 20.2 29.6 2.2 OBJECTIVE with any DMD Mean EDSS score (SD) 2.1 (1.9) 2.9 (1.22) .0 (1.26) 2.9 (1.2) A post hoc analysis to examine efficacy outcomes of 0.7 0.7 Mean number of Probability Event-free 1. (.) 1. (.2) 0.6 (1.) 0. (2.) Probability Event-free T1 Gd+ lesions (SD) in CLARITY patients who are Cladribine tablets 10 mg Mean number of 0. (22.) 2.6 (19.9) 26. (1.9) 2. (1.9) (3.5 mg/kg cumulative dose over 2 years) ≤30 >30 T2 lesions (SD) 0.6 0.6 OR years old years old 1 12 2 36 48 60 2 84 96 1 12 2 36 48 60 2 84 96 vs. Placebo Cladribine tablets 3.5 mg/kg Placebo Time in Weeks Time in Weeks at the time of enrollment RESULTS Placebo Cladribine tablets 3.5 mg/kg Cladribine Tablets Reduced ARR over 96 Weeks vs. Placebo in Both Age Groups Over 96 weeks vs. placebo Based on confirmed EDSS progression. A 3- or 6-month confirmed increase in a subject’s EDSS score occurs when a subject’s EDSS score increases from baseline and the increase is sustained over consecutive ≤30 years 0 years visit(s) for a period equal to or greater than 3 or 6 months (i.e., 83 or 166 days). Note: Percent differences highlighted represent the numerical differences in proportion of patients 3-month confirmed EDSS progression-free at 96 weeks, based on Kaplan-Meier estimates METHODS ● Analyses were performed by age subgroup (≤30 and >30 years), a relatively young age cut-off 0.16 0.1 with adequate N needed for analyses, and by treatment (cladribine 3.5 mg/kg tablets vs. placebo) 66* 53%* 3- and 6-Month confirmed EDSS progression (≤30 years and >30 years) ● This post hoc analysis was exploratory and not pre-specified, therefore P values below 0.05 are considered nominal Mean ARR 0. Mean ARR 0.1 Study Design1 Cladribine Tablets Improved NEDA Attainment Using 3-month Confirmed EDSS Progression YEAR 1 YEAR 2 0 0.1 0.2 0.3 0.4 0.5 0.6 0 0.1 0.2 0.3 0.4 0.5 0.6 (1st 48 weeks) (2nd 48 weeks) Placebo Cladribine tablets 3.5 mg/kg in Both Age Groups *P<0.0001 placebo compared with cladribine tablets Screening Note: ARR and % reduction estimated using a Poisson regression model of the relapse count as dependent variable with fixed effect for treatment group and region and the log of time on study as offset ≤30 years 0 years Placebo OR: 1.6 OR: .9 Cladribine Tablets Increased Proportion of Relapse-free Patients in Both Age Groups (95% CI: 4.3, 49.7) (95% CI: 2.7, 5.6) 2.9 P<0.0001 . P<0.0001 . Patients with ≤30 years 0 years .9 . RRMS (n=1326) R 1. randomized 111 Cladribine tablets 3.5 mg/kg 0. .6 111 9. 21.1 1.2 2.9 0. 1. Cladribine tablets 5.25 mg/kg .1 . .0 . 6.2 66.1 .9 1.9 .1 . 92.2 . 6.2 Endpoints: 6.1 Placebo Cladribine tablets 3.5 mg/kg Placebo Cladribine tablets 3.5 mg/kg Relapse-free status MRI activity NEDA Placeo NEDA Cladribine EDA Placebo EDA Cladribine Unknown Placebo Unknown Cladribine A NEDA status (no relapse, Placebo Cladribine tablets 3.5 mg/kg Placebo Cladribine tablets 3.5 mg/kg NEDA: Patients with NEDA over 96 weeks for all 4 components: relapse, 3-month confirmed EDSS progression, new T1 Gd+ lesions, active T2 lesions 3- and 6-month confirmed EDSS 3- or 6-month confirmed EDSS Relapse-free Placeo Relapse-free Cladribine lacebo Relapse Cladribine Unknown Placebo Unknown Cladribine EDA: Patients with Disease Activity on ≥1 component are considered to have Evidence of Disease activity (EDA) progression, or MRI activity) Unknown: Patients with NEDA but missing ≥1 component progression NEDA using 6-month confirmed EDSS progression results were similar and not shown Note: Proportions are Kaplan-Meier estimates at last event (Week 96). Early withdrawals before Day 587 without an event are considered unknown; withdrawals on or after Day 587 without an event are Note: OR (95% CI) and P value are based on logistic regression with treatment and region as fixed effect; subjects with unknown NEDA not included considered event-free. Unknowns not imputed but included in the denominator Abbreviations: ARR, annualized relapse rate; CI, confidence interval;DMD, disease-modifying drug; EDSS, Expanded Disability Status Scale; Gd+, gadolinium-enhanced; mo, month; MRI, magnetic resonance imaging; NEDA, No Evidence of Disease Activity: OR, odds ratio; RRMS, relapsing-remitting MS; SD, standard deviation Acknowledgments: This study was sponsored by EMD Serono, Inc., USA, an affiliate of Merck KGaA, Darmstadt, Germany. Writing and editorial support for the preparation of this poster was provided by Jenna Steere, PhD and Nick White of Ashfield Healthcare Communications (New York, NY, USA); funding was provided by EMD Serono, Inc., USA, an affiliate of Merck KGaA, Darmstadt, Germany. EMD Serono, Inc. reviewed and provided feedback on the poster. The authors had full control of the poster, and provided their final approval of all content. Disclosures: MSF has received honoraria or consultation fees from Actelion, Bayer HealthCare, Biogen Idec, Chugai, EMD Inc., Canada (an affiliate of Merck KGaA, Darmstadt, Germany), Genzyme, Hoffman La Roche, Novartis, Sanofi, and Teva Pharmaceuticals USA. GP has received speaker honoraria and/or consulting fees from Alexion, Biogen Idec, Celgene, EMD Serono, Inc., USACopies (an affiliate of this of Merckposter KGaA, obtained Darmstadt, through Germany), QR Novartis,(Quick Roche/Genentech,Response) code Sanofi-Genzyme; are for personal and hasuse received only andresearch may support not be(to thereproduced institution) fromwithout Abbvie, written Adamas, permission Alkermes, Biogen of the Idec, authors. EMD Serono, Inc., USA (an affiliate of Merck KGaA, Darmstadt, Germany), Roche/Genentech, Sanofi Genzyme, Novartis, and Teva. NDS has received honoraria and consultation fees from Merck Serono S.p.A., Italy (an affiliate of Merck KGaA, Darmstadt, Germany), Teva Pharmaceutical Industries, Novartis Pharma AG, Bayer Schering AG, Sanofi-Aventis, and Serono Symposia International Foundation.JA is an employee of EMD Serono Research & Development Institute, Inc. Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany. SS is an employee of Sanofi USA, Cambridge, MA, USA; former employee of EMD Serono Research & Development Institute, Inc. Billerica, MA, USA, an affiliate of Merck KGaA, Darmstadt, Germany. YH is an employee of Merck KGaA, Darmstadt, Germany. AG is an employee of Merck, Aubonne, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany. CL is an employee of EMD, Inc. Mississauga, ON, Canada, an affiliate of Merck KGaA, Darmstadt, Germany.GG has received speaker honoraria and consulting fees from Abbvie, Actelion, Atara Bio, Almirall, Bayer Schering Pharma, Biogen Idec, FivePrime, GlaxoSmithKline, GW Pharma, Merck & Co., Merck KGaA (Darmstadt, Germany), Pfizer Inc., Protein Discovery Laboratories, Teva Pharmaceutical Industries Ltd, Sanofi-Genzyme, UCB, Vertex Pharmaceuticals, Ironwood, and Novartis; and has received research support unrelated to this study from Biogen Idec, Merck & Co, Novartis, and Ironwood.
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