An oral, selective tyrosine kinase 2 inhibitor, BMS-986165, improves quality of life in psoriasis: results from a Phase 2 study Fall Clinical Dermatology Conference • October 17–20, 2019 • Las Vegas, NV, USA D Thaçi,1 K Papp,2 K Gordon,3 A Morita,4 M Gooderham,5 P Foley,6 E Alemao,7 R Kisa,7 Y Elbez,8 H Ren,7 S Banerjee7 1University of Lübeck, Lübeck, Germany; 2K Papp Clinical Research and Probity Medical Research, Waterloo, ON, Canada; 3Medical College of Wisconsin, Milwaukee, WI, USA; 4Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 5SKiN Centre for Dermatology, Queen’s University and Probity Medical Research, Peterborough, ON, Canada; 6The University of Melbourne, St Vincent’s Hospital Melbourne & Probity Medical Research, Skin & Cancer Foundation Inc, Melbourne, Victoria, Australia; 7Bristol-Myers Squibb, Princeton, NJ, USA; 8Excelya, Boulogne-Billancourt, France • Psoriasis is a chronic immune-mediated disease, which impairs patients’ physical health and worsens their health-related quality of life (QoL).1–3 • Improvement in health-related QoL, as measured by the Dermatology Life Quality Index (DLQI),4 is an important patient-reported outcome in psoriasis trials. ○ The DLQI questionnaire includes 10 questions on how much the skin problem affected life over the previous week. ○ DLQI overall (total) scores range from 0 to 30, with higher scores indicating worse health-related QoL.4 • BMS-986165 is an oral, selective inhibitor of tyrosine kinase 2, an intracellular kinase that activates cytokine signaling pathways of interleukin-23 and Type I interferons that are central in the pathophysiology of psoriasis5,6 and other immune-mediated disorders.7,8 • In a 12-week, placebo-controlled, Phase 2 trial (NCT02931838), BMS-986165 was effective and demonstrated acceptable safety in patients with moderate to severe plaque psoriasis.9 ○ With BMS-986165 at doses 3 mg twice daily (BID), 67–75% of patients achieved Psoriasis Area and Severity Index (PASI) 75 at Week 12 (primary endpoint), versus 7% of those treated with placebo (P0.001). ○ PASI 75 and PASI 90 responses were similar in the highest dose groups (3 mg BID, 6 mg BID, 12 mg once daily [QD]), providing the rationale for combining data from these 3 groups in subsequent analyses.9 INTRODUCTION • To evaluate: ○ DLQI responses, both overall and for individual questions, and ○ the time course of DLQI improvements and PASI or static Physicians Global Assessment (sPGA) score of 0 or 1 (0/1) responses OBJECTIVE Study design, endpoints, and patients • In this Phase 2 trial, adults with moderate to severe plaque psoriasis were randomized equally to receive 1 of 5 BMS-986165 doses or placebo for 12 weeks (Figure 1). Analysis of DLQI score • The proportion of patients achieving DLQI overall score 0/1, indicative of no impact on the patient’s health-related QoL,10 over time to Week 12 was calculated. • Changes from baseline in DLQI overall score over time to Week 12 were computed. ○ For patients with DLQI overall scores 2 at baseline, scores of 0/1 to individual questions on the 10-question DLQI form (each scored 0–3) were analyzed. ○ In addition, scores of 0 for Question 1 were analyzed in a similar fashion. • A score of 0 on DLQI Question 1 reflects the effect of the most relevant symptoms of psoriasis (itching, soreness, skin pain, and stinging) on health-related QoL. • Time courses of PASI 75, PASI 90, sPGA 0/1, and DLQI were analyzed. METHODS Improvement in the overall DLQI score and individual DLQI questions over time • Change from baseline over time to Week 12 in the overall DLQI scores were more pronounced with the higher doses of BMS-986165 versus placebo (Figure 2). • In patients with a baseline DLQI score of 2 for an individual question, 85.7–97.4% in the combined dose group versus 42.9–76.9% in the placebo group improved to a score of 0/1 for that question at Week 12 (Figure 3). Time course analysis of DLQI, PASI 75, PASI 90, and sPGA 0/1 • An improvement as early as Week 4 (earliest time point evaluated) was observed in the proportion of patients attaining scores of 0/1 on DLQI overall (Figures 4A, 5A, and 6A), and a score of 0 (‘not at all’) on the individual DLQI Question 1 (‘How itchy, sore, painful, or stinging has your skin been?’), which reflects the most relevant subjective symptoms of psoriasis (Figures 4B, 5B, and 6B). • At Week 12, the proportion of patients with a score of 0/1 on DLQI overall and 0 on Question 1 was as high as 64% and 59%, respectively, in the combined BMS-986165 dose group versus 4% and 9%, respectively, with placebo. • Improvements in scores of 0/1 on DLQI overall or 0 on DLQI Question 1 occurred concordantly with improvements in PASI 75 (Figure 4), PASI 90 (Figure 5), and sPGA 0/1 (Figure 6) with each dose over time. Patients • Overall, 267 patients were randomized and treated in this study, and 224 (84%) completed the 12-week treatment period. ○ 134 patients were included in the 3 highest dose groups, 3 mg BID (n=45), 6 mg BID (n=45), and 12 mg QD (n=44), which had similar PASI responses; 45 patients were included in the placebo group. • Patient demographics and disease characteristics, including baseline DLQI scores, were generally comparable across treatment groups.9 ○ Baseline mean (standard deviation) DLQI scores were as follows: placebo: 12.6 (7.1); 3 mg BID: 12.5 (5.5); 6 mg BID: 11.3 (6.5); 12 mg QD: 13.0 (7.4). RESULTS References 1. Mahil SK et al. Semin Immunopathol. 2016;38:11-27. 2. Armstrong AW et al. PLoS One. 2012;7:e52935. 3. Dubertret L et al. Br J Dermatol. 2006;155:729-736. 4. Finlay AY, Khan GK. Clin Exp Dermatol. 1994;19:210-216. 5. Tokarski JS et al. J Biol Chem. 2015;290:11061-11074. 6. Gillooly K et al. Arthritis Rheumatol. 2016;68(suppl 10):abstract 11L. 7. Harden JL et al. J Autoimmun. 2015;64:66-73. 8. Yao Y et al. PLoS One. 2008;3:e2737. 9. Papp K et al. N Engl J Med. 2018;379:1313-1321. 10. Hongbo Y et al. J Invest Dermatol. 2005;125:659-664. Acknowledgments This study was sponsored by Bristol-Myers Squibb. Professional medical writing and editorial assistance was provided by Katerina Kumpan, PhD, at Caudex and was funded by Bristol-Myers Squibb. Disclosures DT: grant/research support: AbbVie, Almirall, Amgen, Biogen Idec, BioSkin, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chugai, Dermira, Dignity, Eli Lilly, Forward Pharma, GlaxoSmithKline, Janssen Cilag, LEO Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi, Sandoz-Hexal, UCB; consultant: AbbVie, Almirall, Bristol-Myers Squibb, Celgene, Dignity, Galapagos, LEO Pharma, Lilly, Novartis, Pfizer, UCB; honoraria: AbbVie, Almirall, Amgen, BioSkin, Celgene, Dignity, Janssen, La Roche Posay, LEO Pharma, Merck Sharp & Dohme, Novartis, Pfizer, Sandoz-Hexal, Sanofi, UCB; advisory board: AbbVie, BioSkin, Bristol-Myers Squibb, Celgene, Dignity, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen Cilag, LEO Pharma, MorphoSys, Novartis, Pfizer, Sandoz, Sanofi, UCB. KAP: speakers bureau: AbbVie, Amgen, Astellas, Celgene, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, LEO Pharma, Merck (Merck Sharp & Dohme), Novartis, Pfizer, Valeant; grant/research support: AbbVie, Akros, Allergan, Amgen, Anacor, Arcutis, AstraZeneca, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, LEO Pharma, MedImmune, Meiji Seika Pharma, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis/Genzyme, Takeda, UCB, Valeant; consultant: AbbVie, Akros, Amgen, Arcutis, Astellas, AstraZeneca, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, CanFite, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Forward Pharma, Galderma, Genentech, Janssen, Kyowa Hakko Kirin, LEO Pharma, Meiji Seika Pharma, Merck (Merck Sharp & Dohme), Merck Serono, Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis/Genzyme, Takeda, UCB, Valeant; honoraria: AbbVie, Akros, Amgen, Baxter, Boehringer Ingelheim, Celgene, Coherus, Eli Lilly, Forward Pharma, Galderma, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, Merck (Merck Sharp & Dohme), Merck Serono, Novartis, Pfizer, Takeda, UCB, Valeant; scientific officer/steering committee/advisory board: AbbVie, Akros, Amgen, Anacor, Astellas, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dow Pharma, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, Merck (Merck Sharp & Dohme), Merck Serono, Novartis, Pfizer, Regeneron, Sanofi-Aventis/Genzyme, Valeant. KG: grant/research support, consultant: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, Janssen, Novartis, Pfizer, Sun, UCB. AM: grant/research support, consultant, speakers bureau: AbbVie, Eli Lilly, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi-Tanabe, Novartis. MG: speakers bureau, consultant, investigator/advisor: AbbVie, Akros, Amgen, Arcutis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Hakko Kirin, LEO Pharma, Merck, MedImmune, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Takeda, UCB, Valeant. PF: speakers bureau, consultant, investigator, advisor, travel grants: 3M/iNova/Valeant, Abbott/AbbVie, Amgen, Biogen Idec, Boehringer Ingelheim, Botanix, Bristol-Myers Squibb, Celgene, Celtaxsys, CSL, Cutanea, Dermira, Eli Lilly, Galderma, GlaxoSmithKline/Stiefel, Janssen, LEO Pharma/Peplin, Novartis, Regeneron, Sanofi Genzyme, Schering-Plough/Merck Sharp & Dohme, Sun Pharma, UCB, Wyeth/Pfizer. EA, RK, HR, SB: employees, shareholders: Bristol-Myers Squibb. YE: consultant: Bristol-Myers Squibb. Previously presented at the European Academy of Dermatology and Venerology (EADV), held October 9–13, 2019. • Treatment with BMS-986165 improved health-related QoL, as measured by the proportions of patients in whom the disease had no impact on health-related QoL (scores of 0/1 for DLQI overall), as well as those without bothersome subjective symptoms of psoriasis (score of 0 for DLQI Question 1). • Improvements were seen as early as 4 weeks after starting treatment and were concordant with PASI 75, PASI 90, and sPGA 0/1 responses. • Phase 3 studies in psoriasis (POETYK PSO Phase 3 program; NCT03624127, NCT03611751) are ongoing to further assess BMS-986165 in larger groups of patients. CONCLUSIONS BMS-986165: 3 mg QOD (n=44) Screening Day -28 4 weeks’ screening 12-week treatment phase 30-day safety follow-up • Active moderate to severe psoriasis (PASI �12, BSA �10, sPGA �3) • Total 267 patients Week 1 Day 1 first dose Week 12 Day 85 primary endpoint PASI 75 BMS-986165: 3 mg QD (n=44) BMS-986165: 3 mg BID (n=45) BMS-986165: 6 mg BID (n=45) BMS-986165: 12 mg QD (n=44) Placebo (n=45) Follow-up Figure 1: Study design. BID=twice daily; BSA=body surface area; PASI=Psoriasis Area and Severity Index; QD=every day; QOD=every other day; sPGA=static Physician Global Assessment. Scientific Content On-demand Copies of this poster obtained through Quick Response (QR) code are for personal use only and may not be reproduced without permission from Fall Clinical Dermatology Conference and the authors of this poster. Links are valid for 30 days after the congress presentation date. To receive a copy of this poster Scan QR code via a barcode reader application M ea n ch an ge fr om b as el in e in D LQ I Week -20 -15 -10 -5 0 5 0 2 6 104 8 12 3 mg BID Placebo 6 mg BID 12 mg QD BMS-986165 Figure 2: Mean change from baseline in DLQI overall score over time. Error bars represent SD. BID=twice daily; DLQI=Dermatology Life and Quality Index; QD=every day; SD=standard deviation. Patients (%) Itchy, sore, painful, or stinging skin Embarrassed/self-conscious Limited activities like shopping, or looking after home or garden Skin influenced clothes you wear Affected social or leisure activities Limited sports Prevented you from working or studying Created problems with your partner, close friends, or relatives Caused sexual difficulties Treatment for your skin has been a problem 0 10 20 30 40 50 60 70 80 90 100 Placebo BMS-986165 combined* Figure 3: Frequency of patients with response of 0/1 on individual DLQI questions at Week 12 among those with response of 2 for that question at baseline (from patients who had DLQI overall score 2 at baseline). *BMS-986165 3 mg BID, 6 mg BID, and 12 mg QD combined. BID=twice daily; DLQI=Dermatology Life and Quality Index; QD=every day. 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 P at ie nt s (% ) Weeks 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 P at ie nt s (% ) Weeks DLQI overall: score 0/1PASI 75 3 mg BID (n=45) Placebo (n=45) 6 mg BID (n=45) 12 mg QD (n=44) BMS-986165 DLQI Question 1*: score 0PASI 75 3 mg BID (n=45) Placebo (n=45) 6 mg BID (n=45) 12 mg QD (n=44) BMS-986165 A B Figure 4: Time course of PASI 75 and (A) DLQI overall or (B) DLQI Question 1* responses. *Question 1 states, ‘Over the last week, how itchy, sore, painful, or stinging has your skin been?’ BID=twice daily; DLQI=Dermatology Life and Quality Index; PASI 75=75% improvement in Psoriasis Area and Severity Index score; QD=every day. Figure 5: Time course of PASI 90 and (A) DLQI overall or (B) DLQI Question 1* responses. Figure 6: Time course of sPGA 0/1 and (A) DLQI overall or (B) DLQI Question 1* responses. *Question 1 states, ‘Over the last week, how itchy, sore, painful, or stinging has your skin been?’ BID=twice daily; DLQI=Dermatology Life and Quality Index; PASI 90=90% improvement in Psoriasis Area and Severity Index score; QD=every day. *Question 1 states, ‘Over the last week, how itchy, sore, painful, or stinging has your skin been?’ BID=twice daily; DLQI=Dermatology Life and Quality Index; QD=every day; sPGA=static Physicians Global Assessment. 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 P at ie nt s (% ) Weeks 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 P at ie nt s (% ) Weeks DLQI overall: score 0/1PASI 90 3 mg BID Placebo 6 mg BID 12 mg QD BMS-986165 3 mg BID Placebo 6 mg BID 12 mg QD BMS-986165 DLQI Question 1*: score 0PASI 90 A B 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 P at ie nt s (% ) Weeks 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 P at ie nt s (% ) Weeks DLQI overall: score 0/1sPGA 0/1 DLQI Question 1*: score 0sPGA 0/1 A B 3 mg BID Placebo 6 mg BID 12 mg QD BMS-986165 3 mg BID Placebo 6 mg BID 12 mg QD BMS-986165