Long-term Efficacy and Safety of Brodalumab in Patients With Psoriasis Whose Disease Did Not Respond to Prior Biologics Mark Lebwohl,1 Lawrence Green,2 Miriam Bettencourt,3 Scott Fretzin,4 Abby Jacobson5 1Icahn School of Medicine at Mount Sinai, New York, NY; 2George Washington University School of Medicine, Washington, DC; 3University of Nevada, Las Vegas, NV; 4 Dawes Fretzin Dermatology Group, Indianapolis, IN; 5Ortho Dermatologics (a division of Bausch Health US, LLC), Bridgewater, NJ 39th Annual Fall Clinical Dermatology Conference® for Dermatologists • October 17-20, 2019 • Las Vegas, NV INTRODUCTION • Patients with psoriasis who experience treatment failure to, or whose disease does not respond to, biologic therapies over time may encounter medical or economic consequences, including higher mean total healthcare-related costs and increased use of other medications1 • Brodalumab is a fully human anti–interleukin-17 receptor A monoclonal antibody that is efficacious in treating moderate- to-severe psoriasis2 • It is crucial to understand the efficacy of subsequent biologic treatment in individuals whose disease did not respond to initial biologic treatment OBJECTIVES • To assess long-term efficacy and safety of brodalumab in 2 multi center randomized clinical trials (AMAGINE-2/-3; ClinicalTrials.gov identifiers: NCT01708603, NCT01708629) in patients with moderate-to-severe plaque psoriasis whose disease did not respond to 1, 2, or ≥3 prior biologics3 METHODS • In AMAGINE-2/-3, patients were initially randomized to brodalumab 140 or 210 mg every 2 weeks, ustekinumab, or placebo during a 12-week induction phase (Figure 1) – At week 12, patients who received brodalumab were re-randomized to either the same or a different brodalumab regimen, patients receiving ustekinumab continued on ustekinumab, and patients receiving placebo were switched to brodalumab 210 mg every 2 weeks • At week 52, all patients entered the long-term extension phase and received brodalumab • 408 patients from AMAGINE-2/-3 who received any dose of brodalumab through week 120 were included in this post-hoc analysis, which comprised – 160 patients with a lack of response to 1 biologic – 112 patients with a lack of response to 2 biologics – 136 patients with a lack of response to ≥3 biologics • Skin clearance was monitored by psoriasis area and severity index 75% improvement (PASI 75), PASI 90, and PASI 100 responses • Safety was summarized by exposure-adjusted treatment- emergent adverse event (TEAE) rates RESULTS Efficacy • Among patients whose disease did not respond to 1, 2, or ≥3 prior biologics, skin clearance rates were comparable from weeks 52 to 120 in those achieving PASI 75 (Figure 2A), PASI 90 (Figure 2B), and PASI 100 (Figure 2C) • In an observed analysis at week 52, PASI 75 response rates in patients whose disease did not respond to 1, 2, or ≥3 prior biologics were 86.4%, 87.2%, and 85.3%, respectively – PASI 90 response rates were 71.2%, 75.6%, and 72.5%, respectively – PASI 100 response rates were 42.4%, 50.0%, and 41.2%, respectively • At week 120, observed PASI 75 response rates were 82.1%, 84.3%, and 93.2% in patients whose disease did not respond to 1, 2, or ≥3 prior biologics, respectively – PASI 90 response rates were 64.1%, 74.5%, and 79.7%, respectively – PASI 100 response rates were 50.0%, 54.9%, and 54.2%, respectively Safety • Across all years, exposure-adjusted TEAE rates per 100 patient- years in patients receiving brodalumab whose disease did not respond to 1, 2, or ≥3 prior biologics were 359.0, 297.6, and 383.2, respectively (Table 1) Acknowledgments: This study was sponsored by Ortho Dermatologics. Medical writing support was provided by MedThink SciCom and funded by Ortho Dermatologics. Ortho Dermatologics is a division of Bausch Health US, LLC. References: 1. Foster et al. J Manag Care Spec Pharm. 2016;22:396-405. 2. Siliq [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America, LLC; 2017. 3. Lebwohl et al. N Engl J Med. 2015;373:1318-1328. CONCLUSIONS • Skin clearance rates were comparable in patients whose disease did not respond to 1, 2, or ≥3 prior biologics through week 120 • These data demonstrate that brodalumab is efficacious and well tolerated for long-term treatment of moderate-to-severe psoriasis in patients with lack of response to prior biologic therapies, including those with lack of response to ≥3 prior biologics © 2019. All Rights Reserved. ► ► ► ► Day 1 Week 12 Week 16 Week 52 ► Week 120 Ustekinumab Brodalumab 210 mg Q2W Brodalumab 210 mg Q2W Ustekin umabPlacebo Ustekin umabUstekinumab Brodalumab 210 mg Q2W Induction Maintenance Long-term extension Week 16 inadequate responders Brodalumab 210 mg Q2W Brodalumab 140 mg Q2W Brodalumab 140 mg Q4W Brodalumab 140 mg Q8W Brodalumab 140 mg Q2W R 2:2:2:1 R 2:2:1:1 Brodalumab 210 mg Q2W (rescue) Figure 1. AMAGINE-2/-3 study design. R, randomization; Q2W, every 2 weeks; Q4W, every 4 weeks; Q8W, every 8 weeks. Table 1. Exposure-Adjusted Rates of TEAEs in Patients Who Received Any Dose of Brodalumab Did not respond to 1 prior biologic N=160; 269.4 PY Did not respond to 2 prior biologics N=112; 189.2 PY Did not respond to ≥3 prior biologics N=136; 215.0 PY Grade ≥2 535 (198.6) 317 (167.6) 430 (200.0) Grade ≥3 37 (13.7) 24 (12.7) 32 (14.9) Serious AEs 23 (8.5) 11 (5.8) 10 (4.7) Fatal AEs 1 (0.4) 0 0 AE, adverse event; n, number of adverse events; N, number of patients; PY, total patient-years of exposure; TEAE, treatment-emergent adverse event. Values are the number of AEs (exposure- adjusted event rate per 100 patient-years). Weeks 12 24 36 52 72 84 96 108 1200 Weeks 12 24 36 52 72 84 96 108 1200 87.2 84.3 85.3 93.2 0 20 40 60 80 100 R es po nd er s, % Did not respond to 1 prior biologic Did not respond to 2 prior biologics Did not respond to ≥3 prior biologics Did not respond to 1 prior biologic Did not respond to 2 prior biologics Did not respond to ≥3 prior biologics Did not respond to 1 prior biologic Did not respond to 2 prior biologics Did not respond to ≥3 prior biologics N1 = 160 156 147 142 118 120 117 113 97 78 N1 = 112 109 102 93 86 85 78 79 66 51 N1 = 136 134 122 114 102 95 94 90 81 59 A 71.2 64.1 75.6 74.5 72.5 79.7 0 20 40 60 80 100 R es po nd er s, % N1 = 160 156 147 142 118 120 117 113 97 78 N1 = 112 109 102 93 86 85 78 79 66 51 N1 = 136 134 122 114 102 95 94 90 81 59 B 42.4 50.0 50.0 54.9 41.2 54.2 0 20 40 60 80 100 R es po nd er s, % N1 = 160 156 147 142 118 120 117 113 97 78 N1 = 112 109 102 93 86 85 78 79 66 51 N1 = 136 134 122 114 102 95 94 90 81 59 C 82.1 Weeks 12 24 36 52 72 84 96 108 1200 86.4 Figure 2. PASI 75 (A), PASI 90 (B), and PASI 100 (C) responses in patients whose disease did not respond to 1, 2, or ≥3 prior biologics. Error bars indicate the 95% confidence interval. N1, number of patients who had a valid measurement value at the specified week; PASI 75, 90, and 100, psoriasis area and severity index 75%, 90%, and 100% improvement.