Disclosures and Acknowledgments MW: advisory/consulti ng fees from - - PDF document

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• M. Williams

May 31, 2019

Mitzi Williams,1 Lilyana Amezcua,2 Stephen Krieger,3 Annette Okai,4 Darin T. Okuda,5 Ray Su,6 Sami Fam,6 James B. Lewin,6 Cynthia C. Jones6

Real-world Efficacy of Delayed-release Dimethyl Fumarate in Black or African American Patients With Multiple Sclerosis: 24-Month Interim Results From ESTEEM

Consortium of Multiple Sclerosis Centers | May 28 – June 1, 2019 | Seattle, WA

1Morehouse School of Medicine, Atlanta, GA, USA; 2University of Southern California, Keck School of Medicine,

Los Angeles, CA, USA; 3Icahn School of Medicine at Mount Sinai; NYC, USA; 4Multiple Sclerosis Treatment Center

• f Dallas, TX, USA; 5UT Southwestern Dallas, TX, USA; 6Biogen, Cambridge, MA, USA

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Disclosures and Acknowledgments

• MW: advisory/consulti ng fees from Biogen, Celgene, EMD Serono, Genentech, Teva Neuroscience, and Sanofi-

Genzyme; speaker fees from Biogen, Genetech, Sanofi-Genzyme, and Teva

• LA: advisory/consulting fees from Celgene and Genzyme; research support from Biogen and Novartis
• SK: advisory/consulting fees from Biogen, EMD Serono, Genentech, Genzyme, Mallinckrodt, MedDay

, Novartis, Teva, and TG Therapeutics; fees for nonpromotional disease state speaking for Biogen and EMD Serono

• AO: advisory/consulting fees from Biogen, Celgene, EMD Serono, Genentech, Genzyme, and Novartis; research

support from Biogen, Novartis, Sanofi-Genzyme, and TG Therapeutics; speaker fees from Biogen, Genentech, Novartis, Sanofi-Genzyme, and Teva

• DTO: advisory/consulting fees from Biogen, Celgene, EMD Serono, Genentech, Genzyme, and Novartis; research

support from Biogen

• RS, SF, JBL, and CCJ: employees of and hold stock/stock options in Biogen
• This study was sponsored by Biogen (Cambridge, MA, USA). Writing and editorial support for the preparation of this

presentation was provided by Excel Scientific Solutions (Southport, CT, USA): funding was provided by Biogen

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Introduction

• Evidence suggests that MS in black or African American (AA) patients has

a more severe inflammatory course than in w hite patients, requiring effective early treatment1,2

Disease progression is significantly faster in black or AA MS patients

MRI = magnetic resonance imaging; MS = multiple sclerosis

• 1. Naismith RT, et al. Mult Scler. 2006:12(6):775-781. 2. Gonzalez Caldito N, et al. Brain. 2018;141(11):3115-3129

Black or AA patients with MS (dotted line); white patients with MS (solid line)

MRI scans show whole brain gray and white matter atrophy twice as fast in black or AA patients compared with white patients Black or AA patients also show faster atrophy of the thalamus, which could be linked to cognitive impairment

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Rationale and Objective

Rationale

• Although data f rom DEFINE/CONFIRM demonstrated a reduction in relapses and disability progression

in AA patients, the sample size (n = 29) was too small to draw def initive conclusions regarding the ef f ects of delayed-release dimethyl fumarate (DMF) in this subgroup

• Data describing the effects of DMF in black or AA patients treated in the real-world setting are limited.

A prev ious retrospective chart review demonstrated that DMF had similar effectiveness in black and Hispanic patients compared with white patients1

• ESTEEM is an ongoing, 5-y ear, multinational, prospective, noninterventional study evaluating the

long-term saf ety and effectiveness of DMF (final results will include data for 5000 patients) Objective

• T
• ev aluate real-world effectiveness of DMF on RRMS disease activity in the overall black or AA

subgroup and in cohorts of black or AA patients with RRMS who switched therapy (received prior interf eron [IFN]/glatiramer acetate [GA] at any time from diagnosis)

RRMS = relapsing-remitting multiple sclerosis

• 1. Zhovtis Ryerson et al. Ther Adv Neurol Disord. 2016;9(6):454-461.

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Study Design and Patients

• This interim analysis of ESTEEM (data cut 09 August 2018) includes patients newly prescribed DMF in routine

practice at ~380 sites globally; patients for this analysis were drawn from the overall ESTEEM population

• Key eligibility criteria

Diagnosis of RRMS and newly prescribed DMF under routine clinical care Age ≥ 12 years (patients < 18 years of age were excluded where enrollment of pediatric patients is prohibited)

• Primary objective: determine the incidence, type, and pattern of AEs and serious AEs leading to treatment

discontinuation

• Secondary objective: assess the effectiveness of DMF on MS clinical relapse activity

Endpoints

• The effectiveness of DMF on MS disease activity was evaluated by assessment of ARR, proportion of patients with

relapse, and distribution of the number of relapses

• The incidence of treatment discontinuation also was assessed

AE = adverse event; ARR = annualized relapse rate; MS = multiple sclerosis; RRMS = relapsing-remitting multiple sclerosis 6

Study Population and Baseline Demographics

Overall N = 3075 Black or AA n = 149 Age, y 41 (11) 43 (11) Age < 40, % 47 40 Age ≥ 40, % 53 60 Female, % 75 81 Region, n (%) United States, including Puerto Rico 901 (29) 144 (97) Western Europe, Canada, New Zealand, and Australia 1898 (62) 5 (3) Eastern Europe 276 (9) 0 (0) EDSS scorea 2.1 (1.5), n = 1448 2.2 (1.9), n = 20 Median (range) duration between most recent relapse and enrollment, mo 6.4 (–2–410) 6.1 (0–159) Median (range) number of relapses in prior year 1 (0–6) 1 (0–4) Mean (SD) DMF treatment duration, mo 14.6 (10.3) 18.7 (14.3) Patients with minimum 1 year follow-up, % 54 58 Patients with minimum 2 year follow-up, % 21 35 Median (range) duration in ESTEEM, mo 17.0 (0–40) 21.6 (1–48) Prior MS treatments, n (%) Glatiramer acetate 807 (39) 61 (58) Intramuscular IFN beta-1a 685 (33) 44 (42) Subcutaneous IFN beta-1a 634 (30) 29 (27) IFN beta-1b 398 (19) 17 (16) Fingolimod 195 (9) 9 (9) Teriflunomide 119 (6) 7 (7) EDSS = Expanded Disability Status Scale; MS = multiple sclerosis All values are mean (SD) unless otherwise noted. aEDSS assessment at enrollment.

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Annualized Relapse Rate: Overall ESTEEM Population and Black or African American Patients

• ARR was significantly lower (p < 0.0001) in the
• verall black or AA population and IFN/GA switch

subgroup examined at 24 months after DMF initiation vs. the 12 months before DMF initiation

ARR = annualized relapse rate

aPatients with missing relapse rate data 12 months before DMF initiation were excluded from the ARR analysis.

Patient Group Proportion of patients without MS relapse by Kaplan- Meier analysis Overall ESTEEM 79% Black or AA 81% Black or AA IFN/GA switch 80%

Proportion of Patients W ithout MS Relapses in the 24 months After DMF

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• A total of 22 black or AA

patients (15%) reported any AE leading to discontinuation, with GI disorders being the most commonly cited (6%)

In ESTEEM, the majority of GI-related discontinuations

• ccurred within the first month
• f treatment

Safety: Adverse Events and Discontinuations

Category, n (% )a Ov erall EST EEM N = 3075 Black or AA n = 149 Any AE leading to treatment discontinuation 502 (16) 22 (15) Lymphocyte count decreased 80 (3) 2 (1) GI disorders 218 (7) 9 (6) Diarrhea 68 (2) 4 (3) Nausea 56 (2) 4 (3) Vomiting 49 (2) 4 (3) Abdominal pain 37 (1) 2 (1) Nervous system disorders 36 (1) 4 (2) Blood and lymphatic system disorders 65 (2) 2 (1) General disorders and administration site conditions 32 (1) 2 (1)

Most Common AEs Leading to DMF Discontinuation in Black or AA Patients

AE = adverse event; GI = gastrointestinal

aAEs occurring in > 1 patient in the black or AA subgroup. AEs coded using Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) and

Preferred Term (PT). Percentages calculated based on total number of patients in each group. A patient was counted only once in each MedDRA SOC or PT.

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Safety: Lymphocyte Count Changes

• In the overall ESTEEM population, among patients

with available lymphocyte data (n = 815), median ALC decreased 37% from baseline to Month 12 T imepoints Median Percentage Change, (n)b From baseline to Month 6

• 22% (59)

From baseline to Month 12

• 20% (39)

From baseline to Month 18

• 16% (28)

From baseline to Month 24

• 24% (25)

a ALC = absolute lymphocyte count

an = number of patients with ALC assessment at the specified timepoint. . bn = number of patients with baseline ALC assessment and an ALC assessment at the specified follow-up visit.

Median Percentage Change in ALC in Black or AA Patients

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• Compared with the 12 months before DMF initiation, ARR was significantly lower in the 24 months

after DMF initiation in the overall black or AA patient cohort, including in patients who switched from prior IFN/GA

The safety profile was consistent with the known profile of DMF and with the safety findings from the overall ESTEEM study population GI disorders were the most common reason for treatment discontinuation This study is limited by its observational open-label design and lack of magnetic resonance imaging baseline data to accurately characterize disease severity of this population

• These safety and effectiveness analyses demonstrate the real-world treatment benefit of DMF

in black or AA patients, consistent with findings in the overall ESTEEM population.

• Similar findings also were observed in a subgroup analysis of Hispanic patients from ESTEEM

(ChineaLate-breaking Poster)

Conclusions