Long-term Efficacy of Brodalumab for the Treatment of Moderate-to-Severe Psoriasis: Data From a Pivotal Phase 3 Clinical Trial Alan Menter,1 Jeff Sobell,2 Jonathan I. Silverberg,3 Mark Lebwohl,4 Shipra Rastogi,5 Radhakrishnan Pillai,6 Robert J. Israel7 1Baylor University Medical Center, Dallas, TX; 2SkinCare Physicians, Chestnut Hill, MA; 3Northwestern University Feinberg School of Medicine, Chicago, IL; 4Icahn School of Medicine at Mount Sinai, New York, NY; 5Ortho Dermatologics, Bridgewater, NJ; 6Dow Pharmaceutical Sciences (a division of Valeant Pharmaceuticals North America LLC), Petaluma, CA; 7Valeant Pharmaceuticals North America LLC, Bridgewater, NJ Winter Clinical Dermatology Conference - Hawaii® • January 12-17, 2018 • Lahaina, HI INTRODUCTION • Brodalumab is a fully human anti–interleukin-17 receptor A monoclonal antibody that antagonizes the action of specific inflammatory cytokines involved in psoriasis1 • Three pivotal phase 3 clinical trials demonstrated the efficacy and safety of brodalumab through 52 weeks in patients with moderate-to-severe psoriasis (AMAGINE-1/-2/-3)1,2 – Brodalumab exhibited superior efficacy vs ustekinumab, with a faster onset of response and a similar safety profile – Data in this poster are from AMAGINE-2 OBJECTIVE • To evaluate the long-term efficacy and safety of brodalumab in patients with moderate-to-severe plaque psoriasis through 120 weeks METHODS Study design • AMAGINE-2 was a 52-week, randomized, double-blind, placebo- and active comparator–controlled clinical trial – Data from this analysis were derived from a long-term open-label extension study through 120 weeks • Patients received brodalumab 210 or 140 mg every 2 weeks (Q2W), ustekinumab, or placebo during a 12-week induction phase, which was followed by a maintenance phase through week 52 (Figure 1) • During the maintenance phase, patients receiving brodalumab were re-randomized to receive a different dose and interval of brodalumab (140 or 210 mg Q2W, Q4W, or Q8W), patients receiving ustekinumab continued on ustekinumab, and patients receiving placebo were switched to brodalumab 210 mg Q2W – At week 16, patients from all brodalumab and ustekinumab groups without adequate response (single static physician’s global assessment [sPGA] score ≥3 or persistent sPGA score of 2 over ≥4 weeks) were eligible for rescue with brodalumab 210 mg Q2W • At week 52, patients who received brodalumab during the maintenance phase continued to receive their maintenance dose of brodalumab, and patients who received ustekinumab switched to brodalumab 210 mg Q2W • Efficacy data are for patients who received brodalumab 210 mg Q2W (the US Food and Drug Administration–approved dose) at any point through week 120 of the long-term extension phase, including patients who received – Placebo during the induction phase – Ustekinumab during the maintenance phase – Brodalumab 140 or 210 mg Q2W during the maintenance phase – Rescue treatment during the maintenance phase • A further subanalysis of efficacy data from patients who received any dose of brodalumab in the induction phase and brodalumab 210 mg Q2W during the maintenance and long-term extension phases is presented • Safety data are for all patients who received ≥1 dose of brodalumab at any point in the study Endpoints/Assessments • Skin clearance was monitored by the sPGA and the psoriasis area and severity index (PASI) • Safety was assessed by monitoring exposure-adjusted treatment- emergent adverse event rate per 100 patient-years RESULTS Patient demographics and baseline disease characteristics • Most patients were male, with a mean (standard deviation) age of 44.6 (12.8) years (Table 1) • A total of 1392 patients entered the long-term extension phase on brodalumab 210 mg Q2W, and 1282 patients had a valid measurement at week 52 Efficacy • Skin clearance response rates at weeks 52 and 120 were similar in patients who received brodalumab 210 mg Q2W during the long-term extension (Figure 2) • In patients who received any dose of brodalumab in the induction phase and brodalumab 210 mg Q2W during the maintenance and long-term extension phases, rates of achieving sPGA 0/1, PASI 75% improvement (PASI 75), PASI 90, and PASI 100 were maintained from weeks 54 to 120 (Figure 3) • Patients who received continuous brodalumab throughout the entire study had a higher rate of achieving PASI 100 compared with patients who received placebo or ustekinumab during the induction phase Safety • A total of 1790 patients received ≥1 dose of brodalumab, with a total time of exposure of 3228.5 years (Table 2) • The safety profile of brodalumab was consistent with that observed in shorter-term studies, and no new safety signals were identified Figure 1. AMAGINE-2 study design. ► ► ► ► Day 1 Week 12 Week 16 Week 52 Ustekinumab 210 mg Q2W 210 mg Q2W Ustekin umabPlacebo Ustekin umabUstekinumab Brodalumab 210 mg Q2W Induction Maintenance Long-term extension 210 mg Q2W 140 mg Q2W 140 mg Q4W 140 mg Q8W Brodalumab 140 mg Q2W R 2:2:2:1 210 mg Q2W (rescue) Q2W, every 2 weeks (with an additional loading dose 1 week after initiation of brodalumab); Q4W, every 4 weeks; Q8W, every 8 weeks; R, randomized. Acknowledgments: Medical writing support was provided by MedThink SciCom and was funded by Ortho Dermatologics. This study was sponsored by Amgen Inc. Author disclosures: The authors disclose past or current financial relationships with the following companies: Menter – AbbVie, Allergan, Amgen, Anacor, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, Janssen Biotech, LEO Pharma, Merck & Co, Neothetics, Novartis, Pfizer, Regeneron, Symbio/Maruho, Vitae, and Xenoport; Sobell – AbbVie, Amgen, Celgene, Janssen, Lilly, Merck, Novartis, and Regeneron; Silverberg – Abbvie, Eli Lilly, Galderma, GlaxoSmithKline, Kiniksa, Leo, Menlo, Pfizer, Realm-1, Regeneron-Sanofi, and Roivant; Lebwohl – Amgen, Anacor, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, Kadmon, LEO Pharma, MedImmune, Novartis, Pfizer, Sun Pharmaceutical Industries, and Valeant Pharmaceuticals North America LLC; Rastogi – Ortho Dermatologics and Valeant Pharmaceuticals North America LLC; Pillai – Dow Pharmaceutical Sciences (a division of Valeant Pharmaceuticals North America LLC); and Israel – Valeant Pharmaceuticals North America LLC. References: 1. Lebwohl et al. N Engl J Med. 2015;373:1318-1328. 2. Papp et al. Br J Dermatol. 2016;175:273-286. CONCLUSIONS • Treatment with brodalumab resulted in substantial psoriatic lesion clearing for >2 years in most patients with moderate-to-severe psoriasis • Skin clearance response rates, as determined by sPGA 0/1, PASI 75, PASI 90, and PASI 100, were maintained from weeks 52 to 120 in patients who received brodalumab 210 mg Q2W • Patients receiving continuous treatment with brodalumab had higher rates of PASI 100 compared with patients who received placebo or ustekinumab during the induction phase PASI 75 90.6 88.4 PASI 90 77.6 76.8 PASI 100 53.3 56.2 R es po nd er s, % 60 0 40 20 80 100 sPGA 0/1 79.2 1015 597 1162 689 995 598 683 438 n 76.6 Week 52 (n=1282) Week 120 (n=779) Figure 2. Skin clearance response rates at weeks 52 and 120 in patients who received brodalumab 210 mg Q2W during the long-term extension. Error bars show the 95% confidence interval. n, number of patients who were responders; PASI 75, 90, and 100, psoriasis area and severity index 75%, 90%, and 100% improvement; sPGA 0/1, static physician’s global assessment score of 0 or 1. Long -term extension 86.5% 79.2% 76.4% 59.0% 0 10 20 30 40 50 60 70 80 90 100 0 20 40 60 80 100 120 140 R es po nd er s, % Weeks sPGA 0/1 PASI 75 PASI 90 PASI 100 120 Week N1= 334 334 316 310 290 291 285 280 234 178 0 12 24 36 52 72 84 96 108 Figure 3. Patients who received continuous brodalumab and achieved sPGA 0/1, PASI 75, PASI 90, and PASI 100 response through week 120. Error bars show 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; sPGA 0/1, static physician’s global assessment score of 0 or 1. Table 1. Baseline Characteristics Full analysis set (N=1831) Age, mean (SD), y 44.6 (12.8) Sex, n (%) Male Female 1258 (68.7) 573 (31.3) Disease duration of psoriasis, mean (SD), y 18.6 (12.2) sPGA score, n (%) 3 4 5 (very severe) 994 (54.3) 723 (39.5) 114 (6.2) SD, standard deviation; sPGA, static physician’s global assessment. Table 2. Exposure-Adjusted Event Rates of Patients Who Received ≥1 Dose of Brodalumab Through the End of the Study n (r) Brodalumab (all patients) (patient-years = 3228.5) (N=1790) All TEAEs Serious AEs AEs leading to drug discontinuation Deaths 9909 (306.9) 247 (7.7) 103 (3.2) 1 (0.1) Most common AEs (>250 events overall) Nasopharyngitis Upper respiratory tract infection Arthralgia Headache 620 (19.2) 499 (15.5) 295 (9.1) 288 (8.9) AE, adverse event; n, number of AEs; r, exposure-adjusted event rate per 100 patient-years (n/patient-year*100); TEAE, treatment-emergent AE. © 2017. All Rights Reserved. 7810_WCDC_104 Week Efficacy - AMAGINE 2_M1-3.indd 1 12/11/17 5:33 PM