PowerPoint Presentation Efficacy and safety of tralokinumab treatment in adults of different racial subgroups with moderate-to-severe atopic dermatitis in three randomized, placebo-controlled phase 3 trials Tiffany Mayo1, April Armstrong2, Leon Kircik3, Jonathan I. Silverberg4, Andrew Blauvelt5, Ben Esdaile6, Shannon Schneider7, Thomas Mark8, Melinda Gooderham9, Andrew F. Alexis10 1University of Alabama at Birmingham, Birmingham, AL, USA; 2Keck School of Medicine of University of Southern California, Los Angeles, CA, USA;3Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4The George Washington School of Medicine and Health Sciences, Washington, DC, USA; 5Oregon Medical Research Center, Portland, OR, USA; 6Whittington Health National Health Service Foundation Trust, London, UK; 7LEO Pharma Inc., Madison, NJ, USA; 8LEO Pharma A/S, Ballerup, Denmark; 9SKiN Centre for Dermatology, Peterborough, ON, Canada; 10Weill Cornell Medicine, New York, NY, USA Table 1. Baseline demographic and disease characteristics of patients by racial subgroup in pooled E1/2/3 Table 2. Summary of AEs through Week 16 in ECZTRA 1/2/3 by racial subgroup Conclusions • In this post hoc analysis, tralokinumab was well-tolerated and improved the signs and symptoms of moderate-to-severe AD, regardless of race, with further improvements up to 52 weeks of treatment • Limitations of this analysis include disparate sample sizes across racial subgroups Tralokinumab improved signs and symptoms of AD across racial subgroups at Week 16 • Across three pooled trials at Week 16, tralokinumab significantly improved efficacy outcomes in the Asian and White subgroups relative to placebo. Similar results were found in the smaller Black subgroup, although statistical significance was not reached for all endpoints vs placebo (Figures 2-3) • Lower efficacy was observed for the Black subgroup relative to Asian and White subgroups when the monotherapy trials were pooled, driven by higher placebo response rates. In contrast, higher efficacy was observed for the Black subgroup relative to Asian and White subgroups in the TCS combination trial References 1. Kaufman B, et al. Exp Dermatol 2018; 27: 340-357. 2. Wollenberg A, et al. Br J Dermatol. 2021; 184(3)437-449. 3. Silverberg J, et al. Br J Dermatol. 2021; 184(3)450-463 Disclosures Tiffany Mayo has served as an investigator or consultant for Eli Lilly, ChemoCentryx, Pfizer, Janssen, Galderma, Bristol Myers Squibb, Acelyrin, Novartis, Leo Pharma, Arcutis, and Procter and Gamble. April Armstrong has served as a research investigator and/or scientific advisor to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, BI, BMS, EPI, Incyte, Leo, UCB, Janssen, Lilly, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, Pfizer, and Modmed. Leon Kircik has served either as an investigator, consultant, or speaker for AbbVie, Almirall, Amgen, Arcutis, Bausch Health Canada, Bristol Myers Squibb, Boehringer Ingelheim, Cellceutix, Celgene, Coherus, Dermavant, Dermira, Eli Lilly, Leo, MC2, Maruho, Novartis, Ortho Dermatologics, Pfizer, Dr Reddy's Laboratories, Sun Pharma, UCB, Taro, and Xenoport. Jonathan I Silverberg reports honoraria as a consultant/advisory board member from LEO Pharma and has acted as a consultant for and/or received grants/honoraria from AbbVie, AnaptysBio, Asana Biosciences, Galderma Research and Development, GSK, Glenmark, Kiniksa, LEO Pharma, Lilly, MedImmune, Menlo Therapeutics, Pfizer, PuriCore, Regeneron, and Sanofi. Andrew Blauvelt has served as a speaker (received honoraria) for AbbVie, Arcutis, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Regeneron, Sanofi, and UCB, served as a scientific adviser (received honoraria) for AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Eli Lilly and Company, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, Leo, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome, and Xencor, and has acted as a clinical study investigator (institution has received clinical study funds) for AbbVie, Acelyrin, Almirall, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Concert, Dermavant, Eli Lilly and Company, Evelo, Evommune, Galderma, Incyte, Janssen, Leo, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma. Ben Esdaile has served either as an investigator, advisor or speaker for LEO Pharma, L’Oréal, Thornton & Ross, Bioderma, Skin + Me and AbbVie. Shannon Schneider and Thomas Mark are employees of LEO Pharma. Thomas Mark owns LEO Pharma stock. Melinda Gooderham has been an investigator, speaker and/or advisor for: AbbVie, Amgen, Akros, AnaptysBio, Aslan, Arcutis, Aristea, Bausch Health, BMS, Boehringer Ingelheim, Celgene, Dermira, Dermavant, Eli Lilly, Galderma, GSK, Incyte, Janssen, Kyowa Kirin, LEO Pharma, MedImmune, Merck, Meiji, Moonlake, Nimbus, Novartis, Pfizer, Reistone, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, and UCB. Andrew F. Alexis has received grants (funds to institution) from LEO Pharma, Novartis, Almirall, Bristol Myers Squibb, Amgen, Vyne, Galderma, Valeant (Bausch Health), Cara, Arcutis, Dermavant, Abbvie, and Castle; has served as an advisory board member or consultant for LEO Pharma, Galderma, Pfizer, Sanofi-Regeneron, Dermavant, Beiersdorf, Ortho, L’Oreal, BMS, Bausch health , UCB, Vyne , Arcutis, Janssen, Allergan, Almirall, Abbvie, Sol-Gel , Amgen, VisualDx, Eli Lilly, Swiss American, and Cutera; and a speaker for Regeneron, Sanofi-Genzyme, Pfizer, and Bristol Myers Squibb. Acknowledgements This analysis was sponsored by LEO Pharma A/S. Medical writing according and editorial support from Alphabet Health by Clair Geary, PhD was funded LEO Pharma A/S, Ballerup, Denmark, to Good Publication Practice guidelines (https://www.ismpp.org/gpp3). This work was previously presented at Fall Clinical 2022. Analyses • As shown in Figure 1, data are presented as: o pooled from ECZTRA 1/2/3 o pooled from ECZTRA 1/2 o ECZTRA 3 • Efficacy outcomes assessed were: o Proportion of patients achieving EASI-75, IGA 0/1 o Change from baseline in EASI, Peak Pruritus NRS, DLQI, and POEM • Data are presented at Week 16 (ECZTRA 1/2/3) and Week 52 (ECZTRA 1/2) • Data are presented as observed regardless of rescue medication use. Multiple imputation was used for missing data • Data were used as per Food and Drug Administration (FDA) label and United States Prescribing Information (USPI; i.e., data from 2 sites were excluded as per FDA guidance) Objective To evaluate the efficacy and safety of tralokinumab +/- TCS versus placebo +/- TCS, by self-identified racial subgroup (Asian, Black, White) in adults with moderate-to-severe AD across three phase 3 trials Materials and Methods Patients and treatment • ECZTRA 1 and 2 were two identically designed, multinational, double-blind, randomized, placebo-controlled, 52-week trials (Figure 1) o Patients were randomized 3:1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks (Q2W) for an initial 16 weeks following a 600 mg loading dose o Patients who achieved IGA 0/1 or EASI-75 at Week 16 with tralokinumab were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for an additional 36 weeks o Rescue treatment could be used at the discretion of the investigator to control intolerable symptoms • In ECZTRA 3, patients were randomized 2:1 to subcutaneous tralokinumab 300 mg + TCS as needed or placebo + TCS as needed Q2W for an initial treatment period of 16 weeks following a 600 mg loading dose o Patients who achieved IGA 0/1 or EASI-75 at Week 16 with tralokinumab were rerandomized to tralokinumab Q2W or every 4 weeks, with TCS as need, for an additional 16 weeks • Patients self-reported their racial subgroup Results Patients, Demographics, and Clinical Characteristics • This post hoc analysis included 1876 patients (USPI population) across ECZTRA 1, 2, and 3 who self-reported their race as Asian, Black, or White (Figure 1, Table 1) • Baseline demographic and disease characteristics were largely balanced between treatment groups and across racial subgroups (Table 1) o AD severity was more moderate in the Black subgroup Introduction • Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with significant disease burden • Although AD is highly prevalent in patients with skin of color, data on the efficacy and safety of AD therapies in these patients is limited since most clinical trials enroll predominately White patients1 o Several standard measures, including EASI, can underestimate AD severity in dark skin1 • Tralokinumab, a specific, high-affinity interleukin-13 inhibitor, is approved in Europe, Canada, and the United States for the treatment of adults with moderate-to-severe AD • ECZTRA 1 (NCT03131648), ECZTRA 2 (NCT03160885), and ECZTRA 3 (NCT03363854) were randomized phase 3 trials assessing the safety and efficacy of tralokinumab or tralokinumab + TCS, as needed. o ECZTRA 1 and 2 were placebo-controlled trials and ECZTRA 3 was placebo + TCS controlled Improvements in efficacy outcomes beyond Week 16 were consistent across racial subgroups • At Week 52 (pooled monotherapy trials), EASI-75 was achieved in 58% of Asian patients, 66% of Black patients, and 63% of White patients (Figure 4) o IGA 0/1 was achieved in 32% of Asian patients, 38% of Black patients, and 38% of White patients (Figure 4) • Improvements in efficacy outcomes after Week 16 were also observed across racial subgroups in ECZTRA 3 (TCS combination trial) Abbreviations adj., adjusted; AE, adverse event; AD, atopic dermatitis; DLQI, dermatology life quality index; E, number of adverse events; EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; n, number of patients achieving the indicated metric, or with ≥1 event; nE, number of events; nP, number of patients, N, number of patients with recorded observation; NRS, numerical rating scale; PYE, patient-years of exposure; Q2W, every 2 weeks; SD, standard deviation; TCS, topical corticosteroids Asian N=407 Black N=134 White N=1335 Tralokinumab (n=291) Placebo (n=116) Tralokinumab (n=95) Placebo (n=39) Tralokinumab (n=992) Placebo (n=343) Mean age, y (SD) 35.2 (12.3) 32.4 (13.2) 39.3 (14.1) 38.6 (16.8) 39.0 (14.8) 38.7 (14.6) Male, n (%) 176 (60.5) 76 (65.5) 38 (40.0) 20 (51.3) 578 (58.3) 209 (60.9) Ethnicity, n (%) Hispanic or Latino 2 (0.7) 3 (2.6) 3 (3.2) 0 68 (6.9) 26 (7.6) Region, n (%) North America Europe Australia Japan Asia 100 (34.4) 20 (6.9) 17 (5.8) 96 (33.0) 58 (19.9) 48 (41.4) 10 (8.6) 7 (6.0) 31 (26.7) 20 (17.2) 86 (90.5) 8 (8.4) 1 (1.1) - - 36 (92.3) 3 (7.7) - - - 284 (28.6) 640 (64.5) 68 (6.9) - - 89 (25.9) 233 (67.9) 21 (6.1) - - Country, n (%) United States Canada Japan 43 (14.8) 57 (19.6) 96 (33.0) 23 (19.8) 25 (21.6) 31 (26.7) 82 (86.3) 4 (4.2) - 35 (89.7) 1 (2.6) - 178 (17.9) 106 (10.7) - 52 (15.2) 37 (10.8) - Patients with IGA 3, n (%) 138 (47.4) 53 (45.7) 61 (64.2) 23 (59.0) 507/1001 (50.6) 169/346 (48.8) Patients with IGA 4, n (%) 153 (52.6) 63 (54.3) 33 (34.7) 15 (38.5) 490/1001 (49.0) 175/346 (50.6) Mean EASI (SD), n 33.2 (15.1) 34.1 (14.2) 29.2 (13.0), 94 33.1 (15.8), 38 31.5 (13.4), 997 31.9 (13.3), 344 Mean SCORAD score (SD) 70.7 (14.7) 71.4 (12.4) 66.4 (12.4), 94 67.6 (12.7), 38 69.7 (12.8), 997 70.8 (12.8), 344 Mean DLQI (SD), n 17.5 (7.1), 289 18.0 (6.6), 114 16.9 (7.1), 94 17.2 (9.7), 37 17.3 (7.0), 984 17.4 (6.9), 342 Mean Worst Pruritus NRS (SD), n 7.8 (1.4), 288 7.8 (1.4), 116 8.1 (1.6), 94 7.7 (1.7), 37 7.7 (1.5), 991 7.9 (1.4), 342 Asian Black White Tralokinumab (n=292) Placebo (n=115) Tralokinumab (n=94) Placebo (n=38) Tralokinumab (n=989) Placebo (n=340) PYE 86.93 33.60 26.92 10.74 294.47 99.54 n (%) Rate (nE/100 PYE) N (%) Rate (nE/100 PYE) N (%) Rate (nE/100 PYE) N (%) Rate (nE/100 PYE) N (%) Rate (nE/100 PYE) N (%) Rate (nE/100 PYE) All AEs 197 (67.5) 570.5 79 (68.7) 633.9 52 (55.3) 542.3 25 (65.8) 512.1 713 (72.1) 753.2 243 (71.5) 772.5 Serious AEs 6 (2.1) 6.9 1 (0.9) 2.9 2 (2.1) 7.4 3 (7.9) 27.9 25 (2.5) 8.8 13 (3.8) 17.0 Severity 161 (55.1) 424.4 61 (53.0) 455.3 45 (47.9) 408.6 17 (44.7) 316.5 590 (59.7) 500.9 181 (53.2) 412.9 Mild Moderate 76 (26.0) 132.2 42 (36.5) 157.7 19 (20.2) 122.5 13 (34.2) 167.6 362 (36.6) 224.4 149 (43.8) 311.4 Severe 11 (3.8) 13.8 5 (4.3) 20.8 3 (3.2) 11.1 2 ( 5.3) 27.9 56 (5.7) 27.8 31 (9.1) 48.2 Leading to withdrawal from trial 7 (2.4) 8.0 5 (4.3) 17.8 5 (5.3) 26.0 1 (2.6) 9.3 20 (2.0) 8.1 8 (2.4) 11.0 Outcome Not Recovered/Not Resolved 39 (13.4) 65.5 18 (15.7) 65.4 14 (14.9) 55.7 7 (18.4) 74.4 156 (15.8) 70.3 43 (12.6) 60.2 Recovering/Resolving 16 (5.5) 18.4 8 (7.0) 23.8 7 (7.4) 26.0 - - 41 (4.1) 15.6 21 (6.2) 26.1 Recovered/Resolved 179 (61.3) 483.1 68 (59.1) 544.6 49 (52.1) 445.7 22 (57.9) 428.3 668 (67.5) 655.4 233 (68.5) 680.1 Recovered/Resolved with Sequelae 3 (1.0) 3.4 - - 1 (1.1) 3.7 - - 14 (1.4) 4.7 2 (0.6) 3.0 Unknown - - - - 2 (2.1) 11.1 1 (2.6) 9.3 20 (2.0) 7.1 3 (0.9) 3.0 Asian Black White Tralokinumab Q2W (n=292) Placebo (n=115) Tralokinumab Q2W (n=94) Placebo (n=38) Tralokinumab Q2W (n=989) Placebo (n=340) N (%) Rate (nE/100 PYE) N (%) Rate (nE/100 PYE) N (%) Rate (nE/100 PYE) N (%) Rate (nE/100 PYE) N (%) Rate (nE/100 PYE) N (%) Rate (nE/100 PYE) All AEs 197 (67.5) 570.59 79 (68.7) 633.90 52 (55.3) 542.36 25 (65.8) 512.12 713 (72.1) 753.21 243 (71.5) 772.59 Infections and infestations 87 (29.8) 141.50 40 (34.8) 196.42 27 (28.7) 133.73 12 (31.6) 139.67 446 (45.1) 237.71 145 (42.6) 232.08 Viral upper respiratory tract infection 28 (9.6) 35.66 9 ( 7.8) 29.76 8 (8.5) 37.15 4 (10.5) 46.56 191 (19.3) 80.14 55 (16.2) 72.34 Conjunctivitis 5 (1.7) 5.75 1 ( 0.9) 2.98 3 (3.2) 14.86 1 (2.6) 9.31 79 ( 8.0) 31.24 9 (2.6) 9.04 Upper respiratory tract infection 17 (5.8) 21.86 6 ( 5.2) 20.83 3 (3.2) 11.14 2 (5.3) 18.62 60 (6.1) 22.07 15 (4.4) 15.07 Skin infection 2 (0.7) 3.45 2 ( 1.7) 5.95 1 (1.1) 3.71 1 (2.6) 9.31 14 (1.4) 5.09 10 (2.9) 10.05 Herpes simplex 5 (1.7) 8.05 1 ( 0.9) 2.98 1 (1.1) 3.71 - - 17 (1.7) 6.45 4 (1.2) 5.02 Figure 3. Change from baseline in EASI, ITCH, POEM, and DLQI by racial subgroup at Week 16 - 30 - 20 - 10 0 Change from baseline - 6 - 4 - 2 0 2 Change from baseline - 20 - 15 - 10 - 5 0 Change from baseline - 20 - 15 - 10 - 5 0 Change from baseline EASI ITCH POEM DLQI Asian; tralokinumab Asian; placebo Black; tralokinumab Black; placebo White; tralokinumab White; placebo ECZTRA 1+2+3 ECZTRA 1+2 ECZTRA 3 Table 3. Summary of selected AEs by SOC and preferred term through Week 16 in ECZTRA 1/2/3 by racial subgroup Figure 1. Summary of tralokinumab ECZTRA trials included in these analyses 52 weeks ECZTRA 1 Tralokinumab monotherapy trials Tralokinumab + TCS combination trial 32 weeks ECZTRA 1+2+3 pooled ECZTRA 1+2 pooled ECZTRA 3 only ECZTRA 3 Self- reported raceECZTRA 2 Asian (N=407) Black (N=134) White (N=1335) Further details of these trials have been previously reported2,3 Asian (N=366) Black (N=99) White (N=1059) Asian (N=41) Black (N=35) White (N=276) ECZTRA 1 (n=802) ECZTRA 2 (n=794) ECZTRA 3 (n=380) Total randomized ECZTRA 1 (n=798) ECZTRA 2 (n=770) ECZTRA 3 (n=368) USPI Population Week 16 Error bars show standard error. Scan to download a copy of this poster Copies of this poster and its content, obtained through this QR code, are for personal use only and may not be reproduced without written permission from the authors The safety profile of tralokinumab treatment was consistent across racial subgroups • Tralokinumab was generally well-tolerated, with a safety profile comparable to placebo and largely consistent across racial subgroups (Table 2) • Rates of adverse events (AEs), serious AEs, and AEs leading to drug withdrawal were low in all treatment groups • Conjunctivitis rates were lower in the Asian and Black relative to White subgroup (Table 3) Figure 4. Percentage of patients achieving EASI-75 and IGA 0/1 by racial subgroup at Week 52 (pooled monotherapy trials) Week 52 (ECZTRA 1+2) EASI- 75 IGA 0 / 1 0 20 40 60 80 63 38 66 38 58 32 R e s p o n d e rs , % Asian Black White Figure 2. Percentage of patients achieving EASI-75 and IGA 0/1 by racial subgroup at Week 16 Asian; tralokinumab Black; tralokinumab White; tralokinumab Asian; placebo Black; placebo White; placebo ECZTRA 1+2+3 ECZTRA 1+2 ECZTRA 3 0 20 40 60 80 Responders, % 0 10 20 30 40 50 Responders, % EASI- 75 IGA 0/ 1 https://www.ismpp.org/gpp3 Slide 1: Efficacy and safety of tralokinumab treatment in adults of different racial subgroups with moderate-to-severe atopic dermatitis in three randomized, placebo-controlled phase 3 trials