Ixekizumab Is Superior to Placebo for the Treatment of Nail, Scalp, and Palmoplantar Psoriasis in Pediatric Patients with Moderate-To-Severe Plaque Psoriasis

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Ixekizumab Is Superior to Placebo for the Treatment of Nail, Scalp, and Palmoplantar Psoriasis in Pediatric Patients With Moderate-to-Severe Plaque Psoriasis

Amy Paller,1 Gabriel A. Magariños,2 Andreas Pinter,3 Jennifer Cather,4 Stuart Keller,5 Claudia Rodriguez Capriles,5 Gaia Gallo,5 Emily Edson-Heredia,5 Lingnan Li,5 Kim Papp6 1Northwestern University, Chicago, USA; 2Psoriahue, Buenos Aires, Argentina; 3University Hospital Frankfurt, Frankfurt, Germany; 4Mindful Dermatology and Modern Research Associates, Dallas, USA; 4Central Dermatology, St. Louis, USA; 5Eli Lilly and Company, Indianapolis, USA; 6K. Papp Clinical Research and Probity Medical Research, Waterloo, and Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Canada

DISCLOSURES: A. Paller has served as an investigator for: AbbVie, AnaptysBio, Eli Lilly and Company, Galderma, Incyte, Leo Pharma, Novartis, Regeneron, and Sanofi, and as a consultant for: AbbVie, Asana BioSciences, Dermavant, Dermira, Galderma, Eli Lilly and Company, Forté Pharma, Leo Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, and Sanofi; G. A. Magariños has served as a speaker, adviser, or investigator for: AbbVie, Amgen, Biogen, Eli Lilly and Company, Janssen Cilag, Novartis, Pfizer, and Sanofi; A. Pinter has been an advisory board member, investigator, and/or speaker for: AbbVie, Janssen Cilag, Leo Pharma, and Novartis and is on the board of directors for Leo Pharma; J. Cather is on the speakers bureau for: AbbVie, Celgene, Eli Lilly and Company, Regeneron, and Sanofi; has received honoraria from: AbbVie, Eli Lilly and Company, Regeneron, and Sanofi; is a consultant for: AbbVie and Eli Lilly and Company; is an investigator for: Celgene, Cutanea, Dermira, Eli Lilly and Company, Galderma Labs, GlaxoSmithKline, Janssen, Merck, Novartis, Regeneron, Sandoz, and Vitae Pharmaceuticals; has received grants from: Celgene, Corrona, Dermira, Janssen, and Novartis; and has received other financial benefits from: AbbVie and Celgene; S. Keller, C. Rodriguez Capriles, G. Gallo, E. Edson-Heredia, and L. Li are current employees and shareholders of Eli Lilly and Company; K. Papp has served as a speaker and/or adviser and/or received grant/research support from: AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas, AstraZeneca, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite, Coherus, Dermira, Dow Pharma, Eli Lilly and Company, Forward Pharma, Galderma, Genentech, Gilead, GlaxoSmithKline, InflaRx, Janssen, Kyowa Hakko Kirin, Leo Pharma, Medimmune, Meiji Seika Pharma, Merck Serono, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Novartis, Pfizer, PRCL Research, Regeneron, Roche, Sanofi-Aventis/Genzyme, Takeda, UCB Pharma, and Valeant/Bausch Health This study was sponsored by Eli Lilly and Company. Medical writing assistance was provided by Samantha Forster, PhD, CMPP, of ProScribe – Envision Pharma Group, and was funded by Eli Lilly and Company BACKGROUND, OBJECTIVE, AND PATIENTS

Background ■ Ixekizumab, a high-affinity monoclonal antibody that selectively Key Inclusion Criteria 1 targets interleukin-17A is approved for moderate-to-severe § Candidates for phototherapy/systemic treatment or plaque psoriasis (PsO) in adults ü considered not adequately controlled by topical ■ Between 30% and 50% of adults with PsO develop PsO before therapies reaching 20 years of age2; those diagnosed at a younger age § Allowed concomitant therapy: topical steroids, have greater burden of disease3 shampoo, moisturizers/emollients and bath oils, and oatmeal bath preparations ■ PsO in children may affect skin sites less common in adults, § Moderate-to-severe plaque PsO for ≥6 months, such as the scalp and nails3 defined as meeting all 3 of the following criteria: ■ Medications available for pediatric patients are limited − PASI ≥12, sPGA ≥3, and BSA ≥10% involvement Objective Key Exclusion Criteria ■ To investigate the efficacy and safety of ixekizumab in pediatric § Have used any therapeutic agent targeted at reducing interleukin-17 or etanercept patients (≥6 and <18 years) with nail, scalp, and palmoplantar X PsO and assess patient-reported PsO severity

1. Liu L, et al. J Inflamm Res. 2016;9:39-50. 2. Bronckers IMGJ, et al. Paediatr Drugs. 2015;17:373-384. 3. Pinson R, et al. Psoriasis (Auckl.). 2016;6:121-129. BSA=body surface area; PASI=Psoriasis Area and Severity Index; PsO=psoriasis; sPGA=static Physician’s Global Assessment STUDY DESIGN AND ANALYSES

Study Design, IXORA-PEDS (NCT03073200) Analyses

171 Double-blind Maintenance Extension § Prespecified outcomes at Week 12 included the proportion a Period Patients Induction Period Period of patients achieving PSSI=0, PPASI=100, NAPSI=0, and IXE Q4W (N=115) PatGA (0,1) − Assessed in patients with scalp PsO (PSSI >0), Open-label IXE Q4W palmoplantar PsO (PPASI >0), fingernail PsO (NAPSI >0), and PatGA >1 at baseline, respectively

Screening § Categorical outcomes were analyzed by Fisher exact test

Randomization PBO Q4W (N=56) − Missing data were imputed using NRI Weeks § Change from baseline was assessed with the ANCOVA –4 to –1 0 12 60 108 model with treatment group, region, baseline sPGA score, Weight-based Dosinga baseline weight category, and baseline value as factors Weight Group Dosing Regimen − Missing data were imputed using LOCF >50 kg 160 mg at Week 0, 80 mg IXE Q4W thereafter 25-50 kg 80 mg at Week 0, 40 mg IXE Q4W thereafter <25 kg 40 mg at Week 0, 20 mg IXE Q4W thereafter

a Etanercept arm not shown. Patients were randomized (2:2:1) to ixekizumab, etanercept, or placebo; etanercept arm included only in countries where it is approved for severe pediatric psoriasis ANCOVA=analysis of covariance; IXE=ixekizumab; LOCF=last observation carried forward; NAPSI=Nail Psoriasis Severity Index; NRI=non-responder imputation; PatGA=Patient Global Assessment of Disease Activity; PBO=placebo; PPASI=Palmoplantar Psoriasis Area and Severity Index; PsO=psoriasis; PSSI=Psoriasis Scalp Severity Index; Q4W=every 4 weeks; sPGA=static Global Physician’s Assessment RESULTS

Baseline Demographics and Disease Characteristics Prespecified Outcomes at Baseline and Week 12 IXE Q4W (N=115) PBO (N=56) IXE Q4W (N=115) PBO (N=56) Age, years 13.7 (3.1) 13.1 (2.8) PSSIa (score range: 0-72) Age, years, median (range) 15.0 (6-17) 13.5 (6-17) Baseline 27.5 (16.9) n=102 29.7 (17.2) n=50 <12 years, n (%) 27 (23.5) 16 (28.6) Week 12 1.6 (3.8) n=97 17.2 (16.3) n=47 ≥12 years, n (%) 88 (76.5) 40 (71.4) Change from baseline at Week 12 –28.5 (2.5) n=102† –13.2 (2.8) n=50 Female, n (%) 63 (54.8) 36 (64.3) PPASIb (score range: 0-72) Weight, kg, median (range) 62.8 (21.5-135.5) 56.9 (21.5-111.2) <25 kg, n (%) 2 (1.7) 1 (1.8) Baseline 8.7 (8.7) n=17 15.4 (21.1) n=9 ≥25 to ≤50 kg, n (%) 29 (25.2) 14 (25.0) Week 12 3.6 (5.4) n=15 16.7 (14.3) n=6 >50 kg, n (%) 84 (73.0) 41 (73.2) Change from baseline at Week 12 –8.4 (2.5) n=16* –0.6 (3.7) n=8 Prior non-bio systemic therapy, n (%) 39 (33.9) 15 (26.8) NAPSIc (score range: 0-80) Prior bio therapy, n (%) 5 (4.3) 2 (3.6) Baseline 33.9 (29.5) n=34 26.5 (20.4) n=12 No prior systemic therapy, n (%) 76 (66.1) 40 (71.4) Week 12 19.1 (19.7) n=30 35.7 (20.2) n=9 Duration of PsO since diagnosis, years 4.7 (3.3) 4.7 (3.0) Change from baseline at Week 12 –14.1 (3.4) n=33* 0.6 (5.6) n=11 BSA, % 27.1 (18.6) 27.1 (17.3) PatGAd (score range: 0-5) BSA, %, median (range) 20.0 (10-90) 20.5 (10-85) Baseline 3.6 (1.1) n=115 3.5 (1.0) n=56 sPGA 3.6 (0.6) 3.5 (0.6) Week 12 0.9 (1.0) n=113 2.7 (1.1) n=53 PASI 19.8 (7.5) 19.7 (8.0) Change from baseline at Week 12 –2.7 (0.3) n=115† –0.8 (0.3) n=56 Scalp PsO, yes/no, n (%)a 103 (89.6) 50 (89.3) Baseline and Week 12 data are mean (standard deviation). Change from baseline data are least Palmoplantar PsO, yes/no, n (%) 17 (14.8) 7 (12.5) squares mean (standard error) Nail PsO, yes/no, n (%)b 43 (37.4) 16 (28.6) a,b,c,d In patients with baseline PSSI >0, PPASI >0, NAPSI >0, or PatGA >1, respectively † CDLQI 8.5 (5.5) 7.4 (4.8) * p<.05, p<.001 vs. placebo Data are mean (standard deviation) unless stated otherwise Bio=biologic; BSA=body surface area; CDLQI=Children's Dermatology Life Quality Index; a Of 153 patients who answered “yes,” 64 were male (IXE Q4W, n=47; PBO, n=17) and 89 were female IXE Q4W=ixekizumab every 4 weeks; NAPSI=Nail Psoriasis Severity Index; PASI=Psoriasis Area (IXE Q4W, n=56; PBO, n=33) and Severity Index; PatGA=Patient Global Assessment of Disease Activity; PBO=placebo; b Of 59 patients who answered “yes,” 31 were male (IXE Q4W, n=22; PBO, n=9) and 28 were female PPASI=Palmoplantar Psoriasis Area and Severity Index; PsO=psoriasis; PSSI=Psoriasis Scalp (IXE Q4W, n=21; PBO, n=7) Severity Index; sPGA=static Physician’s Global Assessment RESULTS AND CONCLUSION

PSSI=0a PPASI=100b ■ At Week 12, ixekizumab was 100 100 significantly superior to placebo IXE Q4W (N=102) PBO (N=50) IXE Q4W (N=17) PBO (N=9) for complete resolution of scalp 80 80 69† PsO and PatGA (0,1) † 60 56 60 47 47 ■ Numerically greater responses 40† 40 40 29 were observed with ixekizumab

16 versus placebo for nail and 20 10 10 20 11 11 11

Response (%), 95% CI 95% (%), Response CI 95% (%), Response palmoplantar PsO resolution 0 0 0 4 8 12 0 4 8 12 ■ Responses to ixekizumab Week Week were rapid − Significant improvements in NAPSI=0c PatGA (0,1)d resolution of scalp PsO and 100 100 IXE Q4W (N=115) PBO (N=56) PatGA (0,1) seen at Week 4 IXE Q4W (N=34) PBO (N=12) † 77† 79 80 80

50† 60 60 Conclusion 40 40 ■ Ixekizumab was rapid and 18 20 15 20 16 effective for complete 9 5 5 Response (%), 95% CI 95% (%), Response 0 0 0 CI 95% (%), Response resolution of scalp, nail, 0 0 0 4 8 12 0 4 8 12 and palmoplantar PsO in Week Week pediatric patients a,b,c,d In patients with baseline PSSI >0, PPASI >0, NAPSI >0, or PatGA >1, respectively; † p<.001 vs. placebo CI=confidence interval; IXE Q4W=ixekizumab every 4 weeks; NAPSI=Nail Psoriasis Severity Index; PatGA=Patient’s Global Assessment of Disease Activity; PBO=placebo; PPASI=Palmoplantar Psoriasis Area and Severity Index; PSSI=Psoriasis Scalp Severity Index