S2010515 FCPANP 2020 Sher_without QR code.indd Presented at the 5th Fall Clinical Dermatology Conference for PAs & NPs (FCPANP). BACKGROUND • Atopic dermatitis (AD) is a chronic infl ammatory skin disease often associated with atopic comorbidities1 • As previously reported, patients with AD have a high prevalence of comorbid atopic conditions, including allergic rhinitis (AR)2 • Dupilumab, a fully human monoclonal antibody, blocks the shared receptor subunit for interleukin (IL)-4 and IL-13, inhibiting signaling of both IL-4 and IL-13, which are key drivers of type 2-mediated infl ammation in multiple diseases, such as AD and AR3 • In dupilumab trials, > 80% of adult patients have reported ≥ 1 comorbid condition, and as many as 50% have reported comorbid AR4 Dupilumab in Adolescents With Moderate-to-Severe Atopic Dermatitis and a History of Allergic Rhinitis: Subgroup Analysis From a Phase 3 Trial (LIBERTY AD ADOL) Lawrence Sher1, Weily Soong2, Randy Prescilla3, Zhen Chen4, Ashish Bansal4 1Peninsula Research Associates, Rolling Hills Estates, CA; 2Alabama Allergy & Asthma Center, Birmingham, AL; 3Sanofi Genzyme, Cambridge, MA; 4Regeneron Pharmaceuticals Inc., Tarrytown, NY; USA Analysis • This analysis includes the subpopulation of patients who reported a history of AR at baseline and the complementary subpopulation without a history of AR • Effi cacy outcomes were analyzed among randomized patients (full analysis set) among the 2 subgroups • Safety was assessed among patients who received ≥ 1 dose of any study drug RESULTS Patients • Of the 251 patients randomized, 166 had a history of AR and 85 did not have a history of AR • Baseline disease characteristics were similar among treatment groups and between subgroups with a history of AR and no history of AR (Table 1) OBJECTIVE • To determine if a history of AR impacts the effi cacy of dupilumab treatment in adolescent patients with moderate-to-severe AD enrolled in a phase 3 trial A P ro p o rt io n o f p a ti e n ts a c h ie vi n g IG A 0 o r 1 a t W e e k 1 6 ( % ) Placebo 0 n = 28 n = 50 22.0 18.5 (6.06, 30.93) n = 34 11.8 11.8 (0.93, 22.59) Dupilumab 300 mg q4w Dupilumab 200 mg or 300 mg q2w 0 20 40 60 80 100 Patients with AR Patients without AR n = 59 25.4 21.9 (9.82, 34.01) n = 23 21.7 21.7 (4.88, 38.60) 3.5 n = 57 B P ro p o rt io n o f p a ti e n ts a c h ie vi n g E A S I- 7 5 a t W e e k 1 6 ( % ) Placebo Dupilumab 300 mg q4w n = 59 n = 23 44.1 35.3 (20.65, 49.94) 34.8 27.6 (5.96, 49.32) Dupilumab 200 mg or 300 mg q2w 0 20 40 60 80 100 Patients with AR Patients without AR n = 34 36.0 27.2 (12.03, 42.42) 41.2 34.0 (14.94, 53.13) n = 50 8.8 n = 57 n = 28 7.1 P ro p o rt io n o f p a ti e n ts a c h ie vi n g ≥ 3 -p o in t im p ro ve m e n t in P e a k P ru ri tu s N R S a t W e e k 1 6 ( % ) F Placebo Dupilumab 300 mg q4w n = 59 n = 23 47.5*** 36.9 (21.90, 51.96) 52.2** 45.0 (22.50, 67.56) Dupilumab 200 mg or 300 mg q2w 0 20 40 60 80 100 Patients with AR Patients without AR n = 34 38.8** 28.2 (12.45, 44.05) 38.2** 31.1 (12.18, 50.01) n = 49 10.5 n = 57 n = 28 7.1 E P ro p o rt io n o f p a ti e n ts a c h ie vi n g ≥ 4 -p o in t im p ro ve m e n t in P e a k P ru ri tu s N R S a t W e e k 1 6 ( % ) Placebo 26.5 21.2 (7.48, 34.87) n = 34 26.5 22.9 (6.55, 39.24) Dupilumab 300 mg q4w Dupilumab 200 mg or 300 mg q2w 0 20 40 60 80 100 Patients with AR Patients without AR n = 59 37.3 31.9 (18.26, 45.61) n = 23 34.8 31.2 (10.57, 51.85) n = 56 n = 28 3.65.4 n = 49 –27.3 –16.7 D % C h a n g e f ro m b a s e lin e in E A S I a t W e e k 1 6 , L S m e a n ( ± S E ) Placebo Dupilumab 300 mg q4w Dupilumab 200 mg or 300 mg q2w –100 –80 –60 –40 –20 0 n = 23n = 59 –62.5 –45.7 (–70.03, –21.45)–67.8 –40.5 (–55.09, –25.93)–69.6 –52.9 (–74.62, –31.11) –62.2 –35.0 (–50.46, –19.46) n = 34n = 50n = 28n = 57 Patients with AR Patients without AR P ro p o rt io n o f p a ti e n ts a c h ie vi n g ≥ 6 -p o in t im p ro ve m e n t in C D L Q I a t W e e k 1 6 ( % ) H Placebo Dupilumab 300 mg q4w n = 50 n = 21 60.0** 38.0 (20.22, 55.78) 61.9** 46.5 (21.55, 71.49) Dupilumab 200 mg or 300 mg q2w 0 20 40 60 80 100 Patients with AR Patients without AR n = 28 62.8*** 40.8 (22.34, 59.25) 53.6** 38.2 (15.09, 61.29) n = 43 22.0 n = 50 n = 26 15.4 C P ro p o rt io n o f p a ti e n ts a c h ie vi n g E A S I- 5 0 a t W e e k 1 6 ( % ) Placebo n = 28n = 57 Dupilumab 300 mg q4w Dupilumab 200 mg or 300 mg q2w 0 20 40 60 80 100 66.1*** 50.3 (34.97, 65.66) n = 23 47.8** 40.7 (18.15, 63.22) 15.8 7.1 52.0*** 36.2 (19.44, 52.98) n = 34 58.8*** 51.7 (32.58, 70.78) n = 50 n = 59 Patients with AR Patients without AR –20.6 –18.7 G % c h a n g e f ro m b a s e lin e in P e a k P ru ri tu s N R S a t W e e k 1 6 , L S m e a n ( ± S E ) Placebo Dupilumab 300 mg q4w Dupilumab 200 mg or 300 mg q2w –100 –80 –60 –40 –20 0 –47.5*** –26.9 (–39.35, –14.42) –52.0** –33.3 (–52.58, –14.00) –44.4** –23.9 (–37.53, –10.20) –48.9** –30.2 (–50.48, –9.83) Patients with AR Patients without AR n = 34 n = 59 n = 23n = 57 n = 28 n = 50 Figure 2. (A) Proportion of patients achieving IGA 0 or 1 at Week 16; (B) Proportion of patients achieving EASI-75 at Week 16; (C) Proportion of patients achieving EASI-50 at Week 16; (D) Percent change from baseline to Week 16 in EASI; (E) Proportion of patients with ≥ 4-point reduction from baseline in Peak Pruritus NRS at Week 16; (F) Proportion of patients with ≥ 3-point reduction from baseline in Peak Pruritus NRS at Week 16; (G) Percent change from baseline to Week 16 in Peak Pruritus NRS scores; (H) Proportion of patients with ≥ 6-point reduction from baseline in CDLQI through Week 16. Difference vs placebo (95% confi dence interval (CI)) are shown below percent values on top of bar graphs. **P < 0.01; ***P < 0.0001. LS, least squares; SE, standard error. Screening • Age 12–17 years • Moderate-to-severe AD • Inadequately controlled with topical therapies • Scores on IGA ≥ 3, EASI ≥ 16, Peak Pruritus NRS ≥ 4; BSA involvement ≥ 10% Washout • Prior medication Stratification • Body weight (< 60 kg vs ≥ 60 kg) • IGA (3 vs 4) Treatment period (16 weeks) Follow-up period (12 weeks) Loading dose on Day 1a Day –35 to Day –1 Baseline Week 28Week 16 Post-treatment options • Open-label extension • Safety follow-up through Week 28 Placebo (n = 85) Dupilumab q4w 300b mg SC (n = 84) Dupilumab q2w 200/300c mg SC (n = 82) R 1:1:1 Figure 1. Study design. T opical therapy and other systemic AD therapies were prohibited but allowed as rescue treatment for intolerable symptoms. aAll patients receiving q4w, regardless of weight, received a 600 mg loading dose. For q2w, patients with body weight < 60 kg at baseline received a loading dose of 400 mg on Day 1, while patients with body weight ≥ 60 kg received a 600 mg loading dose. bIn the q4w group, patients received 300 mg regardless of body weight. cIn the q2w group, patients with body weight < 60 kg received 200 mg of the study drug; patients with body weight ≥ 60 kg received 300 mg. BSA, body surface area; EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; NRS, Numerical Rating Scale; q2w, every 2 weeks; q4w, every 4 weeks; R, randomization; SC, subcutaneous. CONCLUSIONS • Similar to previous fi ndings in the adult population,5,6 dupilumab improved signs and symptoms of AD in adolescent patients with moderate-to-severe AD regardless of history of AR, indicating that a potentially increased type 2 burden does not impact dupilumab effi cacy METHODS Study design • This was a randomized, double-blinded, placebo-controlled, parallel- group, phase 3 trial of dupilumab in adolescents with moderate-to-severe AD (LIBERTY AD ADOL, NCT03054428, Figure 1)5 Table 1. Baseline disease characteristics by history of AR. Patients with a history of AR Patients without a history of AR Placebo (n = 57) Dupilumab 300 mg q4w (n = 50) Dupilumab 200 mg or 300 mg q2w (n = 59) Placebo (n = 28) Dupilumab 300 mg q4w (n = 34) Dupilumab 200 mg or 300 mg q2w (n = 23) Duration of AD, mean (SD), years 12.4 (3.37) 12.2 (3.08) 12.3 (3.06) 12.0 (3.64) 11.6 (3.32) 12.9 (2.76) IGA score 4, n (%) 33 (57.9) 28 (56.0) 32 (54.2) 13 (46.4) 18 (52.9) 11 (47.8) EASI, mean (SD) 37.3 (14.00) 36.2 (15.05) 35.4 (12.68) 32.0 (13.46) 35.1 (14.68) 34.9 (16.75) SCORAD total score, mean (SD) 71.8 (13.48) 69.7 (13.27) 71.4 (13.12) 67.7 (12.56) 70.0 (15.49) 68.5 (15.80) BSA involvement of AD, mean (SD), % 58.9 (24.34) 58.1 (22.68) 57.1 (19.99) 51.3 (23.28) 55.2 (24.93) 53.0 (24.91) Peak Pruritus NRS, mean (SD) 7.6 (1.65) 7.3 (2.06) 7.5 (1.45) 7.9 (1.58) 7.8 (1.44) 7.7 (1.70) CDLQI, mean (SD) 13.1 (6.69) 15.2 (6.97) 12.4 (5.93) 13.2 (6.90) 14.2 (8.00) 14.5 (6.81) CDLQI, Children’s Dermatology Life Quality Index; SCORAD, SCORing Atopic Dermatitis; SD, standard deviation. Table 2. Safety outcomes in adolescent patients. Patients with, n (%) Placebo (n = 85) Dupilumab 300 mg q4w (n = 83) Dupilumab 200 mg/300 mg q2w (n = 82) TEAE 59 (69.4) 53 (63.9) 59 (72.0) TEAE leading to permanent study discontinuation 1 (1.2) 0 0 Serious TEAE 1 (1.2) 0 0 Death 0 0 0 Most common TEAEsa Dermatitis atopic (PT) 21 (24.7) 15 (18.1) 15 (18.3) Skin infection (adjudicated) 17 (20.0) 11 (13.3) 9 (11.0) Upper respiratory tract infection (PT) 15 (17.6) 6 (7.2) 10 (12.2) Headache (PT) 9 (10.6) 4 (4.8) 9 (11.0) Conjunctivitisb 4 (4.7) 9 (10.8) 8 (9.8) Nasopharyngitis (PT) 4 (4.7) 9 (10.8) 3 (3.7) Infection and infestation (SOC) 37 (43.5) 38 (45.8) 34 (41.5) Injection-site reaction (HLT) 3 (3.5) 5 (6.0) 7 (8.5) Herpes viral infection (HLT) 3 (3.5) 4 (4.8) 1 (1.2) aBy PT, in ≥ 5% of patients in any treatment group. bIncludes the PTs atopic keratoconjunctivitis, conjunctivitis, conjunctivitis allergic, conjunctivitis bacterial, conjunctivitis viral. HLT, MedDRA High Level Term; MedDRA, Medical Dictionary for Regulatory Activities; PT, MedDRA Preferred Term; SOC, MedDRA System Organ Class; TEAE, treatment-emergent adverse event. References: 1. Shrestha S, et al. Adv Ther. 2017;34:1989-2006. 2. Silverberg JI, Simpson EL. Pediatr Allergy Immunol. 2013;24:476-86. 3. Gandhi NA, et al. Nat Rev Drug Discov. 2016;15:35-50. 4. Thaçi et al. J Allergy Clin Immunol. 2018;141 Suppl:AB136. Data presented at 2018 American Academy of Allergy, Asthma & Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress; Orlando, FL, USA; March 2–5, 2018; poster P430. 5. Simpson EL, et al. JAMA Dermatol. 2019 Nov 6 [Epub ahead of print]. doi: https://doi.org/10.1001/jamadermatol.2019.3336 6. Prens E, et al. Allergy. 2018;73(S105): 3-115 AB0140. Data presented at 2018 European Academy of Allergy and Clinical Immunology (EAACI); Munich, Germany; May 26–30, 2018; oral presentation and poster. Acknowledgments: Data fi rst presented at the 2020 Annual Meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI); Philadelphia, PA, USA; March 13–16, 2020. Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifi er: NCT03054428 (LIBERTY AD ADOL). Medical writing/editorial assistance provided by Luke Shelton, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Disclosures: Sher L: Aimmune, Optinose, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme – advisory board member; Regeneron Pharmaceuticals, Inc., Sanofi Genzyme – speaker fees; Aimmune, Amgen, AstraZeneca, Circassia, DBV, Galderma, GSK, Lupin, Merck, Mylan, Novartis, Novo Nordisk, Optinose, Pearl, Pfi zer, Pulmagen, Roxane, Sanofi , Spirometrix, Teva, Vectura, Watson – clinical trial funding. Soong W: AstraZeneca, Regeneron Pharmaceuticals, Inc. – speaker, advisory board member, investigator; AbbVie, Regeneron Pharmaceuticals, Inc. – consultant; AbbVie – investigator; Aimmune, GSK, LEO Pharma, Novartis, Pfi zer, Teva, Vanda Pharmaceuticals – investigator grants; Genentech – investigator grants, honorarium, advisory board member; Stallergenes Greer – advisory board member. Chen Z, Bansal A: Regeneron Pharmaceuticals, Inc. − employees and shareholders. Prescilla R: Sanofi Genzyme − employee, may hold stock and/or stock options in the company. Safety METHODS (CONT.) RESULTS (CONT.) Effi cacy