BMS-986165, an Oral, Selective TYK2 Inhibitor, in the Treatment of Moderate to Severe Psoriasis as Assessed by the Static Physician’s Global Assessment (sPGA)/Body Surface Area (BSA) Composite Tool (sPGA×BSA), a Clinically Useful Alternative to PASI Alice B. Gottlieb,1 Bruce Strober,2 Diamant Thaçi,3 Kenneth Gordon,4 Sudeep Kundu,5 Renata Kisa,5 Lan Wei,5 Subhashis Banerjee,5 Joseph F. Merola6 1Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Yale University, New Haven, CT, and Central Connecticut Dermatology Research, Cromwell, CT, USA; 3Research Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany; 4Medical College of Wisconsin, Milwaukee, WI, USA; 5Bristol-Myers Squibb Company, Princeton, NJ, USA; 6Harvard Medical School, Boston, MA, USA Conclusions • The sPGA×BSA offers more information on the nature of a patient’s disease — ie, on plaque quality and severity as well as BSA — than either measure alone. Cutoffs defining minimal disease activity for sPGA×BSA have been published13 • In patients with moderate to severe psoriasis treated with BMS-986165 or placebo for 12 weeks, similar trends were observed for sPGA×BSA and PASI for all measures evaluated, including percentage mean change and percent improvement from baseline and the proportion of patients achieving sPGA×BSA 75 or PASI 75 • There was a strong correlation between sPGA×BSA and PASI score at Week 12 for all BMS-986165 treatment groups and placebo, and a moderate correlation was observed between sPGA×BSA and DLQI score • These data further support sPGA×BSA as a simple, accurate, and convenient alternative to PASI that can be used in both clinical trial and practice settings2–5 Introduction • The Psoriasis Area and Severity Index (PASI), sPGA, and percentage of BSA involvement are all instruments for the assessment of disease activity in psoriasis, although each has limitations1,2 — PASI is a composite measure requiring a complex multistep formula that restricts its routine use in the clinic; the sPGA assesses erythema, desquamation, and induration of psoriatic plaques independent of the extent of BSA involved with the lesions, while the BSA does not assess the severity of psoriatic lesions1,2 • Several studies have shown that measures that combine some form of investigator global assessment with BSA, such as the product of sPGA and BSA (sPGA×BSA), strongly correlate with PASI in the assessment of moderate to severe psoriasis2–5 • Tyrosine kinase 2 (TYK2) activates intracellular signal transducer and activator of transcription (STAT)- dependent signaling pathways of specific cytokines, including interleukin (IL)-23, IL-12, and Type I interferons, that are involved in the pathogenesis of psoriasis and other immune-mediated disorders6–10 • BMS-986165 is an oral, selective TYK2 inhibitor with a unique mode of binding to the regulatory pseudokinase domain of the enzyme, which provides high functional selectivity for TYK2, rather than the active kinase domain targeted by other tyrosine kinase inhibitors7,11 • In a 12-week, Phase 2 trial (NCT02931838) in adults with moderate to severe plaque psoriasis, BMS-986165 demonstrated a dose-dependent improvement in PASI 75 response and a favorable safety profile12 — At Week 12, PASI 75 responses were highest (67–75%) at doses from 3 mg twice daily (BID) up to 12 mg once daily (QD) versus placebo (7%; P<0.001; primary endpoint) Objective • This post hoc analysis of the Phase 2 trial evaluated the composite sPGA×BSA score compared with PASI score to assess clinical response to BMS-986165 in patients with moderate to severe plaque psoriasis Methods Patient population and study design • The Phase 2 trial included adult patients with plaque psoriasis for ≥6 months and a body mass index of 18–40 kg/m2 who were eligible for phototherapy or systemic therapy and had moderate to severe disease as defined by affected BSA ≥10%, PASI score ≥12, and sPGA score ≥312 • Patients were randomized to 1 of 5 oral doses of BMS-986165 (3 mg every other day, 3 mg QD, 3 mg BID, 6 mg BID, 12 mg QD) or placebo12 • The treatment period was 12 weeks, with an additional 30-day off-treatment follow-up period for safety12 Efficacy assessments and outcomes • Key efficacy assessments included PASI, sPGA, BSA, and the Dermatology Life Quality Index (DLQI) questionnaire — The primary endpoint was PASI 75 at Week 12 • Percentage mean change from baseline to Week 12 in sPGA×BSA and PASI score was assessed for the placebo group and all BMS-986165 dose groups • Spearman correlation coefficients were used to assess the relationship between sPGA×BSA and PASI or DLQI scores at Week 12, as well as between percentage change from baseline in sPGA×BSA and PASI or DLQI scores at Week 12 for all treatment groups. Agreement was based on concordance rates • The proportion of patients achieving 75% improvement in sPGA×BSA (sPGA×BSA 75) or achieving PASI 75 and the percent improvement from baseline in PASI or sPGA×BSA were calculated for patients receiving placebo and for the combined group of patients receiving doses of BMS-986165 that were most effective (≥3 mg BID) Results Patient population • This post hoc analysis included all 267 patients who were randomized and treated in the Phase 2 trial • Patient demographics and baseline disease characteristics were generally similar across treatment groups12 Outcomes • The trend in percentage mean change from baseline to Week 12 across all BMS-986165 treatment groups and the placebo group was similar for sPGA×BSA (Figure 1A) and PASI (Figure 1B) Figure 1. Percentage mean change from baseline by visit in (A) sPGA×BSA and (B) PASI score in patients with moderate to severe plaque psoriasis treated with BMS-986165 or placebo (N=267) A M e an ( SE ) ch an ge f ro m b as e li n e , % 0 -20 -40 -60 -80 -100 Baseline B M e an ( SE ) ch an ge f ro m b as e li n e , % 0 -20 -40 -60 -80 -100 Baseline Percentage mean change from baseline in sPGA×BSA Percentage mean change from baseline in PASI score Week 1 Week 2 Week 4 Week 8 Week 12 Week 1 Week 2 Week 4 Week 8 Week 12 Placebo (n=45) BMS-986165 3 mg BID (n=45) BMS-986165 3 mg QOD (n=44) BMS-986165 6 mg BID (n=45) BMS-986165 3 mg QD (n=44) BMS-986165 12 mg QD (n=44) Data are percentage mean (SE) change from baseline. sPGA×BSA is the product of sPGA and BSA scores. BID=twice daily; BSA=body surface area; PASI=Psoriasis Area and Severity Index; QD=every day; QOD=every other day; SE=standard error; sPGA=static Physician’s Global Assessment. • At Week 12 there was a strong correlation between sPGA×BSA and PASI (Figure 2A; Spearman correlation coefficient = 0.95) and between percent change from baseline in sPGA×BSA and PASI (Figure 2B; Spearman correlation coefficient = 0.95) • At Week 12 there was a moderate correlation between sPGA×BSA and DLQI (Figure 3A; Spearman correlation coefficient = 0.58) and between percent change from baseline in sPGA×BSA and DLQI (Figure 3B; Spearman correlation coefficient = 0.62) • A similar proportion of patients achieved sPGA×BSA 75 and PASI 75 at Week 12 (Figure 4A) • The percent improvement from baseline to Week 12 for BMS-986165 (≥3 mg BID dose groups combined) and placebo was similar for sPGA×BSA and PASI (Figure 4B) 2020 PA & NP Fall Clinical Dermatology Conference, November 13–15, 2020, Orlando, Florida Copies of this poster obtained through Quick Response (QR) code are for personal use only and may not be reproduced without written permission from the authors of this poster. References 1. Spuls PI et al. J Invest Dermatol. 2010;130:933-943. 2. Walsh JA et al. J Am Acad Dermatol. 2013;69:931-937. 3. Duffin KC et al. J Drugs Dermatol. 2017;16:147-153. 4. Gottlieb AB et al. Dermatology. 2019;235:348-354. 5. Merola JF et al. J Invest Dermatol. 2018;138:1955-1961. 6. Watford WT et al. Immunol Rev. 2004;202:139-156. 7. Tokarski JS et al. J Biol Chem. 2015;290: 11061-11074. 8. Volpe E et al. Nat Immunol. 2008;9:650-657. 9. Geremia A et al. J Exp Med. 2011;208:1127-1133. 10. Tucci M et al. Clin Exp Immunol. 2008;154:247-254. 11. Gillooly K et al. Arthritis Rheumatol. 2016;68(suppl10):abstract 11L. 12. Papp K et al. N Engl J Med. 2018;379:1313-1321. 13. Gottlieb AB et al. J Am Acad Dermatol. 2017;77:1178-1180. Acknowledgments • This work was sponsored by Bristol-Myers Squibb Company. Professional medical writing and editorial assistance was provided by Catriona McKay, PhD, and creative assistance during layout was provided by Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, and both were funded by Bristol-Myers Squibb Company. Relationships and Activities • ABG: Grant/research funding (paid to institution): Boehringer Ingelheim, Incyte, Janssen-Ortho, Novartis, UCB, XBiotech; Honoraria or consultation fees (paid to ABG): Abbott (AbbVie), Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Incyte, Janssen Biotech, Janssen-Ortho, Leo Pharma, Lilly ICOS, Novartis, Sun Pharma, UCB, XBiotech, Avotres (no direct compensation received from Avotres); Stock options: XBiotech. • BS: Honoraria or consultation fees: AbbVie, Almirall, Amgen, Arena, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, GSK, Janssen, Kyowa Hakko Kirin, Leo Pharma, Medac, Meiji Seika Pharma, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi-Genzyme, Sun Pharma, UCB; Speaker: AbbVie, Janssen, Lilly, Ortho Dermatologics; Scientific Director (consulting fee): Corrona Psoriasis Registry; Investigator: AbbVie, Corrona Psoriasis Registry, Dermavant, Dermira. • DT: Research support/principal investigator (clinical trials): AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Celgene, Chugai, Dermira, DS-Pharma, Eli Lilly, Galderma, GSK, Janssen-Cilag, Leo Pharma, MSD, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, UCB; Consultant: AbbVie, Almirall, Celgene, Dignity, Galapagos, Leo Pharma, Maruho, Mitsubishi, Novartis, Pfizer, Xenoport; Lectures: AbbVie, Almirall, Amgen, DS-Pharma, Janssen, Leo Pharma, MSD, Novartis, Pfizer, La Roche-Posay, Sandoz-Hexal, Sanofi, Target-Solution, UCB; Scientific advisory board: AbbVie, Amgen, Celgene, DS-Pharma, Eli Lilly, Galapagos, Janssen-Cilag, Leo Pharma, Morphosis, MSD, Novartis, Pfizer, Sandoz, Sanofi, UCB. • KG: Grant support and consulting fees: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, UCB; Consulting fees: Amgen, Almirall, Dermira, Leo Pharma, Pfizer, and Sun Pharma. • JFM: Consultant and/or investigator for Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres, and Leo Pharma. • SK, RK, LW, SB: Employees and shareholders of Bristol-Myers Squibb Company To request a copy of this poster: Scan QR code via a barcode reader application Scientific Content on Demand QR codes are valid for 30 days after the congress date. Figure 2. Correlation between (A) sPGA×BSA and PASI and (B) percentage change from baseline in sPGA×BSA and PASI at Week 12 for all BMS-986165 treatment groups and placebo (N=267) 0 0 5 10 15 20 25 30 35 40 45 50 A Spearman correlation coefficient = 0.95 50 100 150 sPGA×BSA P A SI s co re 200 250 300 -100 -100 -80 -60 -40 -20 0 20 40 60 B Spearman correlation coefficient = 0.95 -75 -50 -25 Change from baseline in sPGA×BSA, % C h an ge f ro m b as e li n e i n P A SI s co re , % 0 5025 10075 sPGA×BSA and PASI at Week 12 Percentage change from baseline in sPGA×BSA and PASI at Week 12 sPGA×BSA is the product of sPGA and BSA scores. Circles represent data points for individual patients. BSA=body surface area; PASI=Psoriasis Area and Severity Index; sPGA=static Physician’s Global Assessment. Figure 3. Correlation between (A) sPGA×BSA and DLQI and (B) percentage change from baseline in sPGA×BSA and DLQI at Week 12 for all BMS-986165 treatment groups and placebo (N=267) A B sPGA×BSA and DLQI at Week 12 Percentage change from baseline in sPGA×BSA and DLQI at Week 12 Spearman correlation coefficient = 0.58 Spearman correlation coefficient = 0.62 sPGA×BSA Change from baseline in sPGA×BSA, % 0 50 100 150 200 250 300 -100 -75 -50 -25 0 5025 10075 0 5 10 15 20 25 30 35 D LQ I sc o re -100 -50 0 50 100 150 200 250 C h an ge f ro m b as e li n e i n D LQ I sc o re , % sPGA×BSA is the product of sPGA and BSA scores. Circles represent data points for individual patients. BSA=body surface area; DLQI=Dermatology Life Quality Index; sPGA=static Physician’s Global Assessment Figure 4. (A) Proportion of patients achieving 75% improvement and (B) percent improvement from baseline in sPGA×BSA or PASI scores at Week 12 for the combined group of patients receiving the 3 most effective BMS-986165 doses (3 mg BID, 6 mg BID, and 12 mg QD) (n=134) vs placebo (n=45) 70.1 78.4 6.7 13.3 A Proportion of patients achieving sPGA×BSA 75 or PASI 75 0 10 20 30 40 50 60 70 80 90 100 P at ie n ts ac h ie vi n g 7 5 % im p ro ve m e n t, % B Percent improvement from baseline in sPGA×BSA or PASI at Week 12 -100 -80 -60 -40 -20 0 20 40 60 80 100 C h an ge f ro m b as e li n e t o W e e k 1 2 , % BMS-986165 3 mg BID, 6 mg BID, and 12 mg QD doses combined (n=134) sPGA×BSA PASI Placebo (n=45) BMS-986165 3 mg BID, 6 mg BID, and 12 mg QD doses combined (n=134) Placebo (n=45) sPGA×BSA is the product of sPGA and BSA scores. sPGA×BSA 75 and PASI 75 are the proportion of patients achieving 75% improvement in sPGA×BSA and PASI scores, respectively. The box whisker plot shows mean, median, other key percentiles, and outliers. BID=twice daily; BSA=body surface area; PASI=Psoriasis Area and Severity Index; QD=every day; sPGA=static Physician’s Global Assessment. http://www.globalbmsmedinfo.com