♦ Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A1 • Demonstrated significant efficacy in the treatment of moderate-to-severe psoriasis2-5 • Maintained improvements in skin clearance for up to 4 years in an open-label extension of a Phase 2 trial6 Efficacy, Health-Related Outcomes, and Safety of Ixekizumab for Up to Five Years of Open-Label Treatment in a Phase 2 Study in Chronic Plaque Psoriasis Andrew Blauvelt,1 Kenneth Gordon,2 Craig Leonardi,3 Claus Zachariae,4 Russel Burge,5 Terri Ridenour,5 Missy McKean-Matthews,5 Sandra Garces,5 Gregory Cameron5 1Oregon Medical Research Center, Portland, USA; 2Medical College of Wisconsin, Milwaukee, USA; 3St. Louis University School of Medicine, St. Louis, USA; 4University Hospital of Copenhagen Gentofte, Copenhagen, Denmark; 5Eli Lilly and Company, Indianapolis, USA METHODS BACKGROUND 2017 Fall Clinical Dermatology Conference (Fall CDC 2017); Las Vegas, Nevada; October 12-15, 2017; Previously presented at EADV 2017 Sponsored by Eli Lilly and Company and/or one of its subsidiaries Disclosures ♦ A. Blauvelt has served as a scientific adviser and/or clinical study investigator for: AbbVie, Aclaris, Allergan, Almirall, Amgen, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly and Company, Genentech/Roche, GlaxoSmithKline, Janssen, Leo Pharma, Merck Sharp & Dohme, Novartis, Pfizer, Purdue Pharma, Regeneron, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB, Valeant, and Vidac, and as a paid speaker for Eli Lilly and Company, Janssen, Regeneron, and Sanofi Genzyme; K. Gordon has served as a consultant for: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly and Company, Janssen, Novartis, and Pfizer, and has received grants from: AbbVie, Amgen, Celgene, Eli Lilly and Company and Janssen; C. Leonardi is on the speaker’s bureau of: AbbVie, Celgene, and Leo Pharma, is a consultant for: AbbVie, Amgen, Dermira, Eli Lilly and Company, Janssen, Leo Pharma, Pfizer, Sandoz, and UCB Pharma, has a conflict with: Actavis, AbbVie, Amgen, Celgene, Coherus, Cermira, Eli Lilly and Company, Galderma, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Sandoz, Stiefel, and Wyeth; C. Zachariae has received honoraria from: Eli Lilly and Company, Novartis, and Pfizer, and has consulted for and participated in advisory boards for: AbbVie, Amgen, Eli Lilly and Company, Janssen-Cilag, Novartis, and Takeda and has been a clinical study investigator for: AbbVie, Amgen, Eli Lilly and Company, Leo Pharma, MSD, Novartis, Regeneron, and Takeda; R. Burge, T. Ridenour, M. McKean-Matthews, S. Garces, and G. Cameron are shareholders and employees of Eli Lilly and Company ♦ This study was sponsored by Eli Lilly and Company. Medical writing services were provided by Samantha Forster, PhD, of ProScribe – part of the Envision Pharma Group, and were funded by Eli Lilly and Company References 1. Liu L, et al. J Inflamm Res. 2016;9:39-50. 2. Leonardi C, et al. N Eng J Med. 2012;366:1190-1199. 3. Gordon KB, et al. J Am Acad Dermatol. 2014;71:1176-1182. 4. Griffiths CE, et al. Lancet. 2015;386:541-551. 5. Gordon KB, et al. N Eng J Med. 2016;375:345-356. 6. Gordon KB, et al. J Eur Acad Dermatol Venereol. 2016;30(Suppl.6):17. 7. Paul C, et al. Br J Dermatol. 2015;173:1378-1399. RESULTS Statistical Analyses ♦ Descriptive statistics (N, mean change, 95% confidence intervals) are provided ♦ Any imputation was performed using the last observation carried forward method Table 1. Baseline Demographics and Disease Characteristics at the Start of Part B (Open-label Extension) Values are mean (standard deviation) unless otherwise stated DLQI=Dermatology Life Quality Index; NAPSI=Nail Psoriasis Severity Index; PASI=Psoriasis Area and Severity Index; PatGA=Patient’s Global Assessment of Disease Activity; PSSI=Psoriasis Scalp Severity Index; VAS=Visual Analog Scale ♦ Throughout the open-label extension, most treatment-emergent adverse events were considered mild or moderate overall ♦ Among the 24 patients experiencing ≥1 treatment-emergent serious adverse event, the most frequent (>4%) were: infections and infestations (n=6, 5.0%), cardiac disorders (n=5, 4.2%) and benign, malignant and unspecified neoplasms (n=5, 4.2%) Table 4. Adverse Events Leading to Discontinuation During Open-label Treatment a The IXE dose was reduced to 80 mg following a protocol amendment to align with the dose regimen used in Phase 3 trials b Includes ongoing patients c Patient consent was required to continue beyond Week 240 IXE=ixekizumab; OLE=open-label extension; PASI 75=Psoriasis Area and Severity Index 75% response; SC=subcutaneous; sPGA=static Physician’s Global Assessment CONCLUSIONS ♦ Ixekizumab provided sustained complete to near complete skin clearance up to 5 years • PASI 75 at Week 260: 83% (LOCF)/98% (observed) • PASI 90 at Week 260: 68% (LOCF)/86% (observed) • PASI 100 at Week 260: 45% (LOCF)/58% (observed) • sPGA (0,1) at Week 240: 64% (LOCF)/78% (observed) • sPGA (0) at Week 240: 48% (LOCF)/59% (observed) ♦ Ixekizumab provided sustained improvements in DLQI and Itch reduction through 4.5 years of treatment • DLQI mean change from baseline at Week 240: -8.3 (LOCF) • Itch VAS mean change from baseline at Week 240: -43.6 (LOCF) ♦ The most common adverse events occurring during the open-label treatment period were consistent with those previously reported in clinical results for patients treated with ixekizumab for a shorter time period1-4 OBJECTIVE ♦ To assess the efficacy, health-related outcomes, and safety of ixekizumab after 5 years of treatment in the open-label extension of a Phase 2 trial (NCT01107457) Figure 3. PASI Response Rates With Ixekizumab Were Maintained Over 5 Years of Open-label Treatment Figure 1. Study Design ♦ Study included patients with chronic plaque psoriasis for ≥6 months, ≥10% body surface area involvement, static Physician’s Global Assessment ≥3, and Psoriasis Area and Severity Index ≥12 Characteristic N=120 Age, years 47.2 (12.3) Male, n (%) 70 (58.3) Body weight, kg 95.4 (26.4) PASI 17.9 (5.9) Nail psoriasis, n (%) 52 (43.3) NAPSI 40.5 (41.7) Scalp psoriasis, n (%) 91 (75.8) PSSI 19.3 (13.3) DLQI 10.9 (6.1) Itch VAS 58.3 (26.0) PatGA (0,1) n (%) 1 (0.8) Incidence, n (%) (N=120) Discontinued due to an adverse event 13 (10.8) Exposure during pregnancy 2 (1.7) Alanine aminotransferase increased 1 (0.8) Hepatic enzyme increased 1 (0.8) Hidradenitis 1 (0.8) Invasive ductal breast carcinoma 1 (0.8) Non-small cell lung cancer metastatic 1 (0.8) Osteomyelitis 1 (0.8) Psoriatic arthropathy 1 (0.8) Pyelonephritis 1 (0.8) Rectal adenocarcinoma 1 (0.8) Rectal adenoma 1 (0.8) Urinary tract obstruction 1 (0.8) Figure 2. Assessments DLQI=Dermatology Life Quality Index; HRQoL=Health-related quality of life; PASI=Psoriasis Area and Severity Index; sPGA=static Physician’s Global Assessment; VAS=Visual Analog Scale Static Physician’s Global Assessment sPGA every 4 weeks to Week 240 Score range: 0 to 5 Proportion of patients achieving sPGA (0,1) Proportion of patients achieving remission of psoriasis plaques by sPGA (0) 4 4 Psoriasis Area and Severity Index PASI every 4 weeks Changes from baseline in PASI • Proportion of patients with at least 75% reduction of PASI (PASI 75) • At least 90% reduction (PASI 90) • 100% reduction (PASI 100) (where PASI 100 refers to complete resolution of plaques) Safety Evaluated up to 260 weeks (5 years) of treatment 260 HRQoL DLQI every 24 weeks to Week 240 Score range: 0 to 30 (less to greater impairment) Score of 0 or 1 = no effect of psoriasis on HRQoL Itch Itch VAS every 24 weeks to Week 240 Score range: 0 (none) to 100 (severe) 24 24 Figure 4. sPGA Response Rates With Ixekizumab Were Maintained Over 4.5 Years of Open-label Treatment Data points shown at Weeks 0, 4, 12, 24, 52, 104, 156, 208, 240 a sPGA was only collected to Week 240, per protocol LOCF=last observation carried forward; sPGA=static Physician’s Global Assessment Figure 5. Ixekizumab Provides Sustained Improvements in DLQI and Itch Reduction in Moderate-to-Severe Psoriasis Through 4.5 Years of Treatment, LOCF Data points shown at Weeks 0, 24, 48, 96, 144, 192, 240 a Defined as the last available value before the first dose in the randomized, placebo-controlled treatment period b DLQI and Itch VAS were only collected to Week 240, per protocol c MCID for DLQI is improvement from baseline ≥57 CI=confidence interval; DLQI=Dermatology Life Quality Index; LOCF=last observation carried forward; MCID=minimal clinically important difference; VAS=Visual Analog Scale Table 2. Incidence of Treatment-emergent Adverse Events Over Time Table 3. Most Common (≥10%) Adverse Events During Open-label Treatment System Organ Class Preferred Term Incidence, n (%) (N=120) Infections and infestations 83 (69.2) Nasopharyngitis 29 (24.2) Sinusitis 17 (14.2) Upper respiratory tract infection 15 (12.5) Urinary tract infection 13 (10.8) Nervous system disorders 22 (18.3) Headache 12 (10.0) Adverse Events, n (%) ≥1 to ≤52 Weeks (N=120, PY=108) >52 to ≤104 Weeks (N=102, PY=95) >104 to ≤156 Weeks (N=90, PY=86) >156 to ≤208 Weeks (N=83, PY=80) >208 to ≤260 Weeks (N=76, PY=72) ≥1 Day (N=120, PY=455) TEAEs 72 (60.0) 68 (66.7) 65 (72.2) 54 (65.1) 38 (50.0) 105 (87.5) SAEs 7 (5.8) 4 (3.9) 6 (6.7) 4 (4.8) 8 (10.5) 24 (20.0) PY=person years; SAE=serious adverse event; TEAE=treatment-emergent adverse event Data points shown at Weeks 0, 4, 12, 24, 52, 104, 156, 208, 240, 260 LOCF=last observation carried forward; PASI 75/90/100=Psoriasis Area and Severity Index 75%/90%/100% response Randomized, Placebo-controlled, Treatment Treatment-free Period Open-label Extension 6 SC doses at Weeks 0, 2, 4, 8, 12, 16 Week 0 to 88: 120 mg SC IXE every 4 weeks Week 92 to 124 onwards: 80 mg SC IXE every 4 weeksa Eligible to enroll in OLE when response < PASI 75 or at Week 32 Patients enrolled N=120 Discontinued treatment during OLE, N=120 Adverse events, n=13 Sponsor decision, n=66 Patient decision, n=26 Lost to follow up, n=10 Other, n=5 All Patients N=142 Completed n=129 Completed Part B (240 weeks) n=74b WEEK 0 WEEK 20 20-32 Wks WEEK 0 of OLE Long-term Open-label Treatment WEEK 240 WEEK 260 Entered Part C (Week 244-260) N=73c Part A Part B Part C DLQI=Dermatology Life Quality Index; LOCF=last observation carried forward; PASI 75/90/100=Psoriasis Area and Severity Index 75%/90%/100% response; sPGA=static Physician’s Global Assessment; VAS=Visual Analog Scale 0 15652 104 208 240 260 0 60 100 80 40 20R es po ns e (% ) Weeks of Open-label Treatment PASI 75 PASI 90 PASI LOCF (N=120) PASI 100 0 15652 104 208 240 260 0 60 100 80 40 20R es po ns e (% ) Weeks of Open-label Treatment PASI 75 PASI 90 PASI Observed PASI 100 N patients 120 758292102 74 65 0 60 100 80 40 20R es po ns e (% ) Weeks of Open-label Treatment sPGA (0,1) sPGA (0) sPGA LOCF (N=120) 0 15652 104 208 240a 0 15652 104 208 240a 0 60 100 80 40 20R es po ns e (% ) Weeks of Open-label Treatment sPGA Observed N patients120 758292102 74 sPGA (0,1) sPGA (0) 0 15652 104 208 240b -60 -20 0 -40 M ea n C ha ng e Fr om B as el in e, a 95 % C I Weeks of Open-label Treatment Itch VAS (N=120) -43.6 0 15652 104 208 240b -15 -5 0 -10 M ea n C ha ng e Fr om B as el in e, a 95 % C I Weeks of Open-label Treatment DLQI (N=120) MCIDc -8.3 FC17PosterLillyBlauveltEfficacyIxekizumab.pdf