ABSTRACT • Introduction: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has previously demonstrated superior efficacy to ustekinumab in the phase 3b CLEAR study of moderate to severe plaque psoriasis.1,2 Here, we report 16-week results from CLARITY, the second head-to-head trial comparing secukinumab with ustekinumab. • Methods: In this ongoing multicenter, head-to-head, double-blind, parallel-group, phase 3b study (NCT02826603), patients were randomized 1:1 to receive subcutaneous secukinumab 300 mg or ustekinumab per label. The co-primary objectives are to demonstrate the superiority of secukinumab over ustekinumab at Week 12 in relation to the proportion of patients with (1) 90% or more improvement from Baseline Psoriasis Area and Severity Index (PASI 90) and (2) a score of 0/1 (clear/almost clear) on the Investigator’s Global Assessment (IGA mod 2011 0/1). Key secondary objectives include demonstrating the superiority of secukinumab over ustekinumab with respect to PASI 75 at Week 4; PASI 75 and 100 at Week 12; PASI 75, 90, 100; and IGA mod 2011 0/1 at Week 16. Missing values were handled by multiple imputation. • Results: At Week 12, both co-primary objectives were met, secukinumab 300 mg (n = 550) was significantly superior to ustekinumab (n = 552) for the proportion of patients achieving both PASI 90 (66.5% vs. 47.9%; P < 0.0001) and IGA mod 2011 0/1 (72.3% vs 55.4%; P < 0.0001) response rates. Additionally, all key secondary objectives were met. At Week 4, PASI 75 response rates were significantly superior with secukinumab 300 mg compared to ustekinumab (40.2% vs 16.3%; P < 0.0001). At Week 16, secukinumab 300 mg demonstrated significantly superior response rates compared to ustekinumab for PASI 75 (91.7% vs 79.8%; P < 0.0001), PASI 90 (76.6% vs 54.2%; P < 0.0001), PASI 100 (45.3% vs 26.7%; P < 0.0001), and IGA mod 2011 0/1 (78.6% vs 59.1%; P < 0.0001). Furthermore, at Week 12, patients receiving secukinumab 300 mg compared to ustekinumab had significantly greater PASI 75 (88.0% vs 74.2%; P < 0.0001) and PASI 100 (38.1% vs 20.1%; P < 0.0001) responses. Safety findings were consistent with the known safety profile of secukinumab. • Conclusions: Secukinumab demonstrated superior results with greater improvements compared to ustekinumab across all study outcomes at Week 4, 12, and 16 in patients with moderate to severe plaque psoriasis. INTRODUCTION • Secukinumab, a fully human monoclonal antibody that inhibits interleukin (IL)-17A, has been shown to have significant efficacy in the treatment of moderate to severe psoriasis and psoriatic arthritis, demonstrating sustained high levels of efficacy with a favorable safety profile3–5 – Secukinumab has also shown efficacy in dedicated trials of scalp, nail, and palmoplantar psoriasis6–8 – Additionally, secukinumab has previously demonstrated superior efficacy to ustekinumab in the phase 3b CLEAR study of moderate to severe plaque psoriasis1 • Here, we report 16-week results from CLARITY, the second head-to- head trial comparing secukinumab with ustekinumab METHODS • CLARITY (NCT02826603) is a multicenter, double-blinded, parallel- group, phase 3b study • Patients were required to have moderate to severe psoriasis at Baseline defined as: – Psoriasis Area and Severity Index (PASI) score of ≥12 and – Body Surface Area (BSA) affected by plaque-type psoriasis ≥10% and – Investigator’s Global Assessment, 2011 modification (IGA mod 2011) ≥3 (based on a scale of 0–4) • Patients were randomized 1:1 to subcutaneous secukinumab 300 mg at Baseline, Weeks 1, 2, and 3, and then every 4 weeks from Week 4 to 48 or subcutaneous ustekinumab (45 mg for patient weighing ≤100 kg or 90 mg for patient weighing >100 kg) at Baseline, Week 4, and then every 12 weeks (Figure 1) • Coprimary objectives of the study are to demonstrate the superiority of secukinumab compared to ustekinumab with respect to: – PASI 90 at Week 12 – IGA mod 2011 0/1 (clear or almost clear skin) at Week 12 • Key secondary objectives will be assessed sequentially by a hierarchical testing strategy, and include measures testing the superiority of secukinumab compared to ustekinumab with respect to the following (shown in hierarchical order): 1. PASI 75 at Week 12 2. PASI 75 at Week 4 3. PASI 90 at Week 16 4. PASI 100 at Week 16 5. IGA mod 2011 0/1 at Week 16 6. PASI 100 at Week 12 7. PASI 75 at Week 16 • Missing values were handled by multiple imputation in this analysis Primary Efficacy Endpoint Screening -4 to Rand. R an do m iz at io n Ustekinumab 45/90 mg1 Secukinumab 300 mg BL 1 2 3 4 8 12 16 20 24 28 32 36 40 44 48 52 F4 EOT F8 Treatment phase Follow-up2 1 = ustekinumab dose is based on body weight at baseline; 45 mg for patient ≤ 100 kg; 90 mg for patient > 100 kg 2 = for patients with premature treatment discontinuation only Follow-up visit F4 is approximately 4 weeks after the EOT visit. Follow-up visit F8 is approximately 8 weeks after the EOT visit = active dose administration; in order to keep the blind, patients will receive placebo administrations at several time points (not shown in this study design figure) BL, Baseline; EOT, end of treatment phase Figure 1. Study Design • A total of 1102 patients were randomized: 550 to receive secukinumab 300 mg and 552 to receive ustekinumab (Figure 2) – The rate of discontinuation was low and balanced between treatment arms Total N = 1102 Patients Randomized Secukinumab 300 mg n = 550 United States 62.7% Adverse events (n = 6) Other (n = 12) Ustekinumab 45/90 mg n = 552 United States 65.6% Adverse events (n = 4) Other (n = 13) Ongoing at Week 16 (n = 532) Discontinued at Week 16 (n = 18) Ongoing at Week 16 (n = 535) Discontinued at Week 16 (n = 17) Figure 2. Patient Disposition • Demographic and baseline disease characteristics were well balanced across patients receiving secukinumab 300 mg and ustekinumab 45/90 mg (Table 1) Table 1. Patient Demographic and Baseline Disease Characteristics Parameter Secukinumab 300 mg (n = 550) Ustekinumab 45/90 mg (n = 552) Mean age, years (SD) 45 (14.1) 45 (14.2) Sex, male, n (%) 356 (64.7) 376 (68.1) Race, white, n (%) 414 (75.3) 410 (74.3) Mean weight, kg (SD) > 100 kg, n (%) 91.0 (24.88) 189 (34.4) 93.0 (24.85) 188 (34.1) Mean PASI score (SD) Score > 20, n (%) 20.8 (8.95) 210 (38.2) 21.3 (9.19) 226 (40.9) BSA affected, % (SD) 29.2 (17.93) 29.5 (17.69) IGA mod 2011 score; severe disease, n (%) 209 (38.0) 239 (43.3) Mean time since first diagnosis of plaque-type psoriasis, years (SD) 16.8 (11.88) 17.3 (13.34) Previous exposure to biologic psoriasis therapy: Yes, n (%) 110 (20.0) 130 (23.6) BSA, body surface area, IGA mod 2011, Investigator’s Global Assessment, 2011 modification; PASI, Psoriasis Area and Severity Index; SD, standard deviation Efficacy • Both coprimary objectives were met: – Secukinumab 300 mg was superior to ustekinumab for the proportion of patients that achieved PASI 90 responses at Week 12 (66.5% vs 47.9%; P < 0.0001) – Secukinumab 300 mg was also superior to ustekinumab for the proportion of patients that achieved IGA mod 2011 0/1 responses at Week 12 (72.3% vs 55.4%; P < 0.0001) • Secukinumab demonstrated statistical superiority compared with ustekinumab at Week 4 and maintained superiority to Week 16 (Figure 3 a-c) Figure 3. IGA mod 2011 0/1 (a), PASI 90 (b), and PASI 100 (c) Response Rates Through Week 16 • Additionally, all key secondary objectives were met in the hierarchical testing strategy (Table 2) Table 2. Hierarchical Efficacy Analysis of Key Secondary Objectives Objectives (shown in order of hierarchical testing strategy) Secukinumab 300 mg (n = 550) Ustekinumab 45/90 mg (n = 552) P value PASI 75 at Week 12 88.0% 74.2% < 0.0001 PASI 75 at Week 4 40.2% 16.3% < 0.0001 PASI 90 at Week 16 76.6% 54.2% < 0.0001 PASI 100 at Week 16 45.3% 26.7% < 0.0001 IGA mod 2011 0/1 at Week 16 78.6% 59.1% < 0.0001 PASI 100 at Week 12 38.1% 20.1% < 0.0001 PASI 75 at Week 16 91.7% 79.8% < 0.0001 IGA mod 2011 0/1, Investigator’s Global Assessment, 2011 modification, clear (0) or almost clear (1); PASI, Psoriasis Area and Severity Index Safety • The safety profile of secukinumab was similar to that reported in previous secukinumab clinical trials – To prevent unblinding of treatment groups, detailed safety results are not presented – Complete safety data will be presented upon completion of the study CONCLUSIONS • Both coprimary objectives were met with secukinumab demonstrating superiority to ustekinumab for PASI 90 and IGA mod 2011 0/1 response rates at Week 12 • Additionally, secukinumab demonstrated robust superiority with greater improvements compared with ustekinumab across all study objectives up to Week 16 • The safety of secukinumab was consistent with the known secukinumab safety profile RESULTS *P < 0.0001 IGA mod 2011 0/1, Investigator’s Global Assessment, 2011 modification, clear (0) or almost clear (1) score; PASI 90/100, Psoriasis Area and Severity Index 90%/100% improvement vs Baseline 0 26.9* 72.3* 78.6* 7.8 55.4 59.1 0 20 40 60 80 100 0 4 8 12 16 Week IGA mod 2011 0/1 a b 0 16.7* 66.5* 76.6* 4.0 47.9 54.2 0 20 40 60 80 100 0 4 8 12 16 Week PASI 90 % R es po nd er s % R es po nd er s 0 5.7* 38.1* 45.3* 0.7 20.1 26.7 0 20 40 60 80 100 0 4 8 12 16 % R es po nd er s Week PASI 100 c Secukinumab 300 mg Ustekinumab 45/90 mg Secukinumab Is Superior to Ustekinumab in Clearing Skin of Patients With Moderate to Severe Plaque Psoriasis: CLARITY, a Randomized, Controlled, Phase 3b Trial Jerry Bagel1, John Nia2, Peter Hashim2, Manmath Patekar3, Ana de Vera3, Sophie Hugot3, Kuan Sheng4, Summer Xia5, Elisa Muscianisi4, Andrew Blauvelt6, Mark Lebwohl2 1Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ, USA; 2Icahn School of Medicine at Mount Sinai, New York, NY, USA; 3Novartis Pharma AG, Basel, Switzerland; 4Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 5Novartis Beijing Novartis Pharma Co. Ltd, Shanghai, China; 6Oregon Medical Research Center, Portland, OR, USA REFERENCES 1. Thaçi D, et al. J Am Acad Dermatol. 2015;73(3):400-409. 2. Blauvelt A, et al. J Am Acad Dermatol. 2017;76:60-69. 3. Bissonnette R, et al. Br J Dermatol. 2017;177(4):1033-1042. 4. Langley RG, et al, for the ERASURE and FIXTURE Study Groups. N Engl J Med. 2014;371(4):326-338. 5. Mease PJ, et al. N Engl J Med. 2015;373(14):1329-339. 6. Bagel J, et al. J Am Acad Dermatol. 2017;77(4):667-674. 7. Reich K, et al. Presented at the 8th International Psoriasis from Gene to Clinic Congress; 30th November – 2nd December, 2017; London, UK. 8. Gottlieb A, et al. J Am Acad Dermatol. 2017;76(1):70-80. DISCLOSURES J Bagel: Investigator and consultant for AbbVie, Amgen, Boehringer-Ingelheim, Sun, Janssen, Leo, Novartis, Celgene, Eli Lilly; consultant and speaker for Valiant; speakers’ bureau for AbbVie, Eli Lilly, Janssen, Leo, Novartis. J Nia and P Hashim: nothing to disclose. M Patekar, A de Vera, S Hugot: Employees of Novartis Pharma AG. K Sheng, E Muscianisi: Employees of Novartis Pharmaceuticals Corporation. S Xia: Employee of Novartis Beijing Novartis Pharma Co. Ltd. A Blauvelt: Scientific adviser and clinical study investigator for AbbVie, Aclaris, Allergan, Almirall, Amgen, Boehringer-Ingelheim, Celgene, Dermavant, Dermira, Inc., Eli Lilly, Genentech/Roche, GlaxoSmithKline, Janssen, Leo, Meiji, Merck Sharp & Dohme, Novartis, Pfizer, Purdue Pharma, Regeneron, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB Pharma, Valeant, Vidac; paid speaker for Eli Lilly, Janssen, Regeneron, Sanofi Genzyme. M Lebwohl: Employee of Mount Sinai, which receives research funds from Amgen, Anacor, Boehringer–Ingelheim, Celgene, Lilly, Janssen Biotech, Kadmon, LEO Pharmaceuticals, Medimmune, Novartis, Pfizer, Sun Pharmaceuticals, and Valeant. ACKNOWLEDGEMENTS The authors thank the patients and their families and all investigators and their staff for participation in this study. Oxford PharmaGenesis, Inc., Newtown, PA, provided assistance with editing, layout, and printing the poster; this support was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ. This research was sponsored by Novartis Pharma AG, Basel, Switzerland. The authors had full control of the contents of this poster. Poster presented at: 13th Annual Winter Clinical Dermatology Conference, Maui, HI, USA; January 12–17, 2018. Download document at the following URL: http://novartis.medicalcongressposters.com/Default.aspx?doc=e8240 And via Text Message (SMS) Text: Qe8240 To: 8NOVA (86682) US Only +18324604729 North, Central and South Americas; Caribbean; China +447860024038 UK, Europe & Russia +46737494608 Sweden, Europe Scan to download a reprint of this poster