Slide 1: Safety and efficacy of dupilumab for moderate-to-severe atopic dermatitis with TCS
Diamant Thaçi, 1 Margitta Worm, 2 Haobo Ren, 3 Steven Weinstein, 3 Neil Graham, 3 Gianluca Pirozzi, 4 Franck Skobieranda, 4 Marius Ardeleanu 3 1 Universität zu Lübeck, Lübeck, Germany; 2 Charite-Universitätsmedzin Berlin, Berlin, Germany; 3 Regeneron Pharmaceuticals, Inc., Tarrytown, USA; 4 Sanofi,
Slide 2: Disclosures
D Thaçi is a consultant for Astellas, Novartis, Regeneron, Celgene, Abbott, Pfizer, Janssen-Cilag, MSD, Leo-Pharma M Worm has nothing to disclose H Ren, S Weinstein, N Graham, and M Ardeleanu are employees and shareholders of Regeneron G Pirozzi is an employee and shareholder of Sanofi F Skobieranda
Slide 3: Introduction
Moderate-to-severe atopic dermatitis (AD) is characterized by eczematous dermatitis with intractable pruritus associated with sleep disturbance and lower quality-of-life For many patients, current therapies are inadequate and can be associated with unwanted side effects IL-4 and IL-13 are thought to
Slide 4: T cells in immune mediated diseases
Foxp3 GATA-3 Th1 Th2 iTreg T naive TGF- IL-10 T cells in immune mediated diseases T cells in immune mediated diseases IFN- IL-2 (IL-10) TNF- LT-a IL-4 IL-5 IL-10 IL-13 (TNF- ) IL-17A IL-17F IL-21 IL-22 (IL-10) (TNF- ) RORc2 IL-22 IL-13 (IL-10) FGF ´ s (TNF- ) ? ALLERGY INFLAMMATION, INFECTION EPITHE
Slide 5: Atopic dermatitis: a disease of altered skin barrier and immune dysregulation
Atopic dermatitis: a disease of altered skin barrier and immune dysregulation Boguniewicz M, Leung DM. Immunol Rev. 2011 Jul;242(1):233-46.
Slide 6: Dupilumab blocks the IL-4/IL-13 receptor/ligand system
B cells, T cells, Monocytes, Eosinophils, Fibroblasts Epithelial cells, Smooth muscle cells, Fibroblasts, Monocytes, Activated B cells Dupilumab blocks the Dupilumab blocks the IL-4/IL-13 receptor/ligand system IL-4/IL-13 receptor/ligand system Type I Receptor Type II Receptor
Slide 7: Study design
Study treatment (weekly SC injection for 4 wks) Screening Safety follow-up (7 wks) n=31 Adult moderate-to- severe AD patients All patients received concomitant treatment with a potent TCS product on a standardized regimen: daily applications to active lesions, followed by applications two days per w
Slide 8: Key inclusion/exclusion criteria
Male or female 18 yrs Chronic AD > 2 yrs IGA 3 SCORAD > 20 10% BSA of AD involvement Active AD lesion(s) for which treatment with potent TCS is indicated Hypersensitivity to TCS 50% of the cumulative lesional surface located on face, flexural, or genital areas (generally unsuitable for treatment wit
Slide 9: Baseline demographics
Mean age, yrs (SD) 37.8 (16.7) 36.0 (11.3) Race, n (%) Caucasian 10 (100%) 20 (95.2%) Non-Caucasian 0 1 (4.8%) Gender, n (%) Male 5 (50.0%) 8 (38.1%) Female 5 (50.0%) 13 (61.9%) Mean BMI, kg/m 2 (SD) 23.92 (3.47) 25.26 (3.26) Baseline demographics Baseline demographics Placebo + TCS (n=10) Dupilumab
Slide 10: Baseline disease characteristics
AD duration, yrs 32.4 (16.8) 30.9 (13.0) EASI score (0-72) 24.10 (12.70) 23.12 (12.35) IGA score (0-5) 3.35 (0.47) 3.43 (0.60) SCORAD score (0-103) 58.20 (13.83) 66.31 (13.01) % BSA of AD 38.85 (24.05) 40.43 (20.91) Pruritus Numeric Rating Scale (NRS) score (0-10) 5.00 (1.40) 6.43 (2.00) EASI=Eczema
Slide 11: Treatment emergent adverse events
Total number of AEs 14 41 Total number of serious AEs 1 0 Deaths 0 0 Number (%) of patients discontinued from study due to AE 1 (10.0%) 0 Number (%) of patients with: Any AE 7 (70.0) 12 (57.1) Any serious AE 1 (10.0) 0 Most common AEs ( 5% in dupilumab groups) • Nasopharyngitis 2 (20.0) 5 (23.8) • H
Slide 12: Dupilumab+TCS significantly improved measures of efficacy vs TCS alone
EASI-50 Responders (Patients achieving 50% Reduction in EASI) Pruritus Numeric Rating Scale 0 10 20 30 40 50 60 70 80 90 100 0 5 10 15 20 25 30 Study Day -80 -70 -60 -50 -40 -30 -20 -10 0 10 20 0 5 10 15 20 25 30 Study Day * p=0.0015 ** p=0.0051 DPL=dupilumab TCS=topical corticosteroids Dupilumab+TC
Slide 13: Dupilumab+TCS significantly improved measures of efficacy vs TCS alone
SCORAD EASI -50 -40 -30 -20 -10 0 0 5 10 15 20 25 30 Study Day -20 -10 0 0 5 10 15 20 25 30 Study Day *p=0.0191 **p=0.0042 DPL=dupilumab TCS=topical corticosteroids Placebo+TCS 300 mg DPL+TCS Placebo+TCS 300 mg DPL+TCS Dupilumab+TCS significantly improved Dupilumab+TCS significantly improved measure
Slide 14: Dupilumab+TCS achieved superior clinical outcomes vs TCS alone
DPL=dupilumab TCS=topical corticosteroids TCS Used Weekly (g) 0 5 15 25 35 45 Wk 1 Wk 2 Wk 3 Wk 4 10 20 30 40 *p=0.1413 IGA Score -3.0 -2.0 -1.0 0 0 5 10 15 20 25 30 Study Day **p=0.0281 Dupilumab+TCS achieved superior Dupilumab+TCS achieved superior clinical outcomes vs TCS alone clinical outcomes
Slide 15: Summary
In this study of adults with moderate-to-severe AD, concomitant treatment with SC dupilumab+TCS exhibited an acceptable safety profile (primary endpoint) Most common treatment-emergent AEs were nasopharyngitis (23.8% vs 20% for placebo), headache and oropharyngeal pain (both14.3% vs 10% for placebo)
Slide 16: Acknowledgements
Marius Ardeleanu Elisa Babilonia Nancee Basinger Warren Brooks Josh Cantor Linda Williams Diamant Thaci Margitta Worm Martin Kaatz Rolf Dominicus Beatrice Gerlach Beate Schwarz Noemi Bakos Lajos Kemeny Marcin Ambroziak Maria Czubek Tara Coughlan Judy Cusick Evelyn Dorsey Kristen Dougherty Chad Fish
Slide 17: BACK UP
BACK UP BACK UP
Slide 18: The march of atopic eczema
Th2 Th1 Th17 Eosinophil Th2 The march of atopic eczema The march of atopic eczema T naive APC (Aero)allergen acute eczema: allergen-specific immune response (Th2, IgE, eosinophils) microbial products/ auto-antigens B cell IFN- IL-13 IL-4 local lymph node dermal vessel chronic eczema: microorganisms,