Poster presented at 13th Annual Winter Clinical Dermatology Conference; January 12–17, 2018; Maui, HI Certolizumab Pegol for the Treatment of Patients with Moderate-to-Severe Chronic Plaque Psoriasis: An Overview of 3 Randomized Controlled Trials Andrew Blauvelt,1 Kristian Reich,2 Mark Lebwohl,3 Daniel Burge,4 Catherine Arendt,5 Luke Peterson,6 Robert Rolleri,6 Alice Gottlieb7 1Oregon Medical Research Center, Portland, OR; 2Dermatologikum Hamburg and SCIderm Research Institute, Hamburg, Germany; 3Icahn School of Medicine at Mount Sinai, New York, NY; 4Dermira, Inc., Menlo Park, CA; 5UCB Pharma, Brussels, Belgium; 6UCB Pharma, Raleigh, NC; 7New York Medical College at Metropolitan Hosptial, New York, NY Introduction • Certolizumab pegol (CZP), the only Fc-free, PEGylated, anti-TNF biologic, has demonstrated promising results in three ongoing, phase 3, randomized, double-blind, placebo-controlled clinical trials in adults with moderate-to-severe chronic plaque psoriasis (CIMPASI-1,1,2 CIMPASI-2,1,2 and CIMPACT3,4) • CZP does not bind the neonatal Fc receptor for IgG (FcRn) and consequently shows minimal placental transfer from mothers to infants5 • CZP is approved for the treatment of adults with rheumatoid arthritis, psoriatic arthritis, Crohn’s disease (US only), ankylosing spondylitis, and axial spondyloarthritis (EU only) • Pooled efficacy and safety results from the first 16 weeks of three 144-week multinational, randomized, double-blind clinical trials evaluating CZP versus placebo are reported here Methods Study Design • CIMPASI-1 (NCT02326298), CIMPASI-2 (NCT02326272), and CIMPACT (NCT02346240) are ongoing phase 3, multicenter, double-blind, placebo-controlled (and active-controlled; CIMPACT only) trials • Patients were randomized to CZP 400 mg every 2 weeks (Q2W), CZP 200 mg Q2W (following 400 mg loading doses at Weeks 0, 2, and 4), or placebo Q2W for 16 weeks (or etanercept [ETN] twice weekly for 12 weeks in CIMPACT only; ETN data are not included in this pooled analysis) (Figure 1) Figure 1. Study Design ETN 50 mg BW (N=170) Washout CZP 200 mg Q2W (N=165)LD CZP 400 mg Q2W (N=167) Placebo Q2W (N=57) 2:2:1 Randomization CIMPASI-1 | CIMPASI-2 N=234 | 227 Double-Blind Maintenance Period Open-Label Treatment • Long-term therapy • CZP-treated responders (PASI 50) continued on the same dose 3:3:3:1 Randomization N=559 Double-Blind Maintenance Period Open-Label Treatment • Long-term therapy • CZP- and ETN-treated responders (PASI 75) re-randomized to CZP or placebo CIMPASI-1 & CIMPASI-2 CIMPACT 0Week 16a,b 48 144 Coprimary Endpoints PASI 75 and PGA 0/1 CZP 200 mg Q2W (N=95 | 91) CZP 400 mg Q2W (N=88 | 87) Placebo Q2W (N=51 | 49) LD 0Week 16c 48 14412 Primary Endpoint PASI 75 aIn CIMPASI-1 and CIMPASI-2, PASI 50 nonresponders at Week 16 entered the Escape Arm for treatment with open-label CZP 400 mg Q2W bUpon entering the Maintenance Period, placebo-treated PASI 75 responders (≥75% reduction in PASI) continued blinded placebo treatment and placebo-treated PASI 50-74 responders (≥50% but <75% reduction in PASI) received CZP 400 mg loading dose at Weeks 16, 18, and 20 and then CZP 200 mg Q2W cIn CIMPACT, PASI 75 nonresponders at Week 16 entered the Escape Arm for treatment with open-label CZP 400 mg Q2W BW, twice weekly; CZP, certolizumab pegol; ETN, etanercept; LD, CZP 400 mg loading dose at Weeks 0, 2, and 4; PASI 50, ≥50% reduction in psoriasis area and severity index (PASI); PASI 75, ≥75% reduction in PASI; PGA 0/1, ‘clear’/‘almost clear’ with ≥2 category improvement in physician’s global assessment; Q2W, every 2 weeks Patients • Eligible patients were ≥18 years of age with moderate-to-severe chronic psoriasis for ≥6 months (psoriasis area severity index [PASI] ≥12, body surface area affected [BSA] ≥10%, and physician’s global assessment [PGA] ≥3 on a 5-point scale) and candidates for systemic psoriasis therapy, phototherapy, and/or photochemotherapy • Patients were excluded if they had previous treatment with CZP (or ETN in CIMPACT) or >2 biologics (including anti-TNF); had a history of primary failure to any biologic or secondary failure to >1 biologic; or had erythrodermic, guttate, or generalized pustular forms of psoriasis Study Assessments • Coprimary endpoints for the pooled analysis were PASI 75 (≥75% reduction in PASI) and PGA 0/1 (’clear’/’almost clear’ with ≥2-category improvement) responder rates at Week 16; PASI 90 (≥90% reduction in PASI) responder rate at Week 16 was a key secondary endpoint; Dermatology Life Quality Index (DLQI) 0/1 responder rate and change from Baseline (CfB) in DLQI versus placebo at Week 16 were also assessed • Safety evaluation included assessment of treatment-emergent adverse events (TEAEs) Statistical Analyses • PASI 75, PGA 0/1, and PASI 90 responder rates were analyzed via a logistic regression model with treatment group, region, study, prior biologic exposure (yes/no), and the interactions study*region and study*prior biologic exposure (yes/ no) as factors using Markov chain Monte Carlo methodology for multiple imputation to address missing data • CfB in DLQI scores are adjusted least squares mean differences from an analysis of covariance (ANCOVA) model with treatment group, region, study, prior biologic exposure (yes/no), and the interactions study*region and study*prior biologic exposure (yes/no) as factors and Baseline DLQI score as a covariate using last observation carried forward (LOCF) imputation • DLQI 0/1 responder rates were summarized descriptively with counts and percentages, where missing data were imputed using nonresponder imputation (NRI) • P-values were not adjusted for multiplicity Results Disposition, Demographics, and Baseline Disease Characteristics • Of 850 patients randomized to CZP or placebo in CIMPASI-1, CIMPASI-2, or CIMPACT, 815 patients (95.9%) completed 16 weeks of treatment (333 [97.4%] for CZP 400 mg Q2W, 336 [95.7%] for CZP 200 mg Q2W, and 146 [93.0%] for placebo; Figure 2) • Patient demographics and Baseline disease characteristics were similar between treatment groups (Table 1) and across trials (data not shown) including Baseline PASI and PGA scores • Across the overall population, approximately one-third of study participants reported prior biologic use (Table 1) Figure 2. Patient Disposition (Week 16) Completed Week 16 Placebo N=157 N=146 (93.0%) N=336 (95.7%) N=333 (97.4%) CZP 200 mg Q2Wb N=351 Randomized N=850a Screened N=1320 CZP 400 mg Q2W N=342 Discontinued Lack of e�cacy Lost to follow-up Consent withdrawn 11 (7.0%) 1 (0.6%) 3 (1.9%) 7 (4.5%) Discontinued Adverse event Lost to follow-up Consent withdrawn Other 15 (4.3%) 3 (0.9%) 4 (1.1%) 7 (2.0%) 1 (0.3%) Discontinued Lack of e�cacy Lost to follow-up Consent withdrawn Other 9 (2.6%) 2 (0.6%) 2 (0.6%) 2 (0.6%) 3 (0.9%) aAn additional 170 patients in CIMPACT were randomized to ETN and are not included in these pooled results bCZP 200 mg Q2W patients received loading dose of CZP 400 mg at Weeks 0, 2, and 4 CZP, certolizumab pegol; ETN, etanercept; Q2W, every two weeks Table 1. Patient Demographics and Baseline Disease Characteristics Placebo (N=157) CZP 200 mg Q2Wc (N=351) CZP 400 mg Q2W (N=342) Demographics Age (years), mean ± SD 46.0 ± 13.3 46.1 ± 13.4 45.2 ± 12.6 Male, n (%) 95 (60.5) 238 (67.8) 210 (61.4) White, n (%) 146 (93.0) 331 (94.3) 322 (94.2) Geographic region, n (%) North America Europe 71 (45.2) 86 (54.8) 136 (38.7) 215 (61.3) 133 (38.9) 209 (61.1) Weight (kg), mean ± SD 92.2 ± 25.8 92.6 ± 22.3 89.2 ± 22.7 BMI (kg/m2), mean ± SD 31.2 ± 7.8 31.0 ± 7.1 30.1 ± 7.1 Baseline Disease Characteristics Duration of psoriasis at screening (years), mean ± SD 17.7 ± 12.7 18.5 ± 13.1 18.2 ± 12.0 Concurrent psoriatic arthritis (self- reported), n (%) 25 (15.9) 59 (16.8) 65 (19.0) PASI, mean ± SD 18.8 ± 6.8 20.3 ± 8.1 20.2 ± 7.5 DLQI,a mean ± SD 13.4 ± 7.7 13.6 ± 7.2 14.5 ± 7.1 BSA (%), mean ± SD 23.5 ± 13.6 25.6 ± 15.9 25.5 ± 14.9 PGA, n (%) 3: moderate 4: severe 112 (71.3) 45 (28.7) 242 (68.9) 109 (31.1) 239 (69.9) 103 (30.1) Any prior systemic psoriasis treatment, n (%) 111 (70.7) 249 (70.9) 247 (72.2) Prior biologic use,b n (%) anti-TNF anti-IL17 40 (25.5) 24 (15.3) 13 (8.3) 106 (30.2) 49 (14.0) 54 (15.4) 107 (31.3) 43 (12.6) 43 (12.6) aFor DLQI: Placebo, N=154; CZP 200 mg Q2W, N=346; CZP 400 mg Q2W, N=340 bPatients may have had exposure to >1 prior biologic but ≤2 per exclusion criteria; 1 patient in the CZP 400 mg Q2W group in CIMPASI-2 had prior exposure to 3 biologics, which was a protocol violation cCZP 200 mg Q2W patients received loading dose of CZP 400 mg at Weeks 0, 2, and 4 BMI, body mass index; BSA, body surface area; CZP, certolizumab pegol; DLQI, Dermatology Life Quality Index; IL, interleukin; PASI, psoriasis area and severity index; PGA, physician’s global assessment; Q2W, every 2 weeks; TNF, tumor necrosis factor Pooled Efficacy • At Week 16, PASI 75 and PGA 0/1 responder rates were significantly greater in the pooled CZP 400 mg Q2W and pooled CZP 200 mg Q2W groups versus placebo, with clinically meaningful differences observed as early as Week 4 for both CZP doses versus placebo (Figure 3 and Figure 4) • Similarly, Week 16 PASI 90 responder rates were significantly greater in the CZP 400 mg Q2W and CZP 200 mg Q2W groups versus placebo, with clinically meaningful differences observed as early as Week 8 for both CZP doses versus placebo (Figure 5) • Meaningful improvements in quality of life, measured by CfB in DLQI and DLQI 0/1 responder rates, were observed in CZP-treated patients versus placebo at Week 16 (Figure 6) Figure 3. Pooled PASI 75 Responder Rates From Baseline to Week 16 R e sp o n d e r R a te ( % ) Week 100 80 60 20 40 0 0 2 4 8 12 16 Placebo (N=157) CZP 200 mg Q2W (n=351) CZP 400 mg Q2W (n=342) 0% 1.6% 3.9% 7.4% 7.5% 2.3% 19.4% 52.8% 68.9% 74.5% 2.6% 16.5% 52.8% 73.0% 80.1% CZP Loading Dosea 74.5% 80.1% **p<0.0001 versus placebo (not adjusted for multiplicity) aCZP 200 mg Q2W patients received loading dose of CZP 400 mg at Weeks 0, 2, and 4 Responder rates are the adjusted predicted probabilities based on logistic regression model with factors for treatment, region, study, prior biologic exposure (yes/no), and the interactions study*region and study*prior biologic exposure (yes/no) where missing data were imputed using multiple imputation (MCMC method) CZP, certolizumab pegol; LD, loading dose of CZP 400 mg Q2W at Weeks 0, 2, and 4; MCMC, Markov chain Monte Carlo; PASI 75, ≥75% reduction in psoriasis area and severity index; Q2W, every 2 weeks Figure 4. Pooled PGA 0/1 Responder Rates From Baseline to Week 16 R e sp o n d e r R a te ( % ) Week 100 80 60 20 40 0 0 2 4 8 12 16 Placebo (N=157) CZP 200 mg Q2W (n=351) CZP 400 mg Q2W (n=342) 0.4% 0.5% 4.7% 3.9% 2.8% 1.9% 13.0% 38.0% 48.2% 54.6% 1.7% 12.3% 39.7% 55.4% 63.7% CZP Loading Dosea 54.6% 63.7% *p<0.05, **p<0.0001 versus placebo (not adjusted for multiplicity) aCZP 200 mg Q2W patients received loading dose of CZP 400 mg at Weeks 0, 2, and 4 Responder rates are the adjusted predicted probabilities based on logistic regression model with factors for treatment, region, study, prior biologic exposure (yes/no), and the interactions study*region and study*prior biologic exposure (yes/no) where missing data were imputed using multiple imputation (MCMC method) CZP, certolizumab pegol; MCMC, Markov chain Monte Carlo; PGA 0/1, ‘clear’/‘almost clear’ with ≥2-category improvement in physician’s global assessment; Q2W, every 2 weeks Figure 5. Pooled PASI 90 Responder Rates From Baseline to Week 16 R e sp o n d e r R a te ( % ) Week 100 80 60 20 40 0 0 2 4 8 12 16 Placebo (N=157) CZP 200 mg Q2W (n=351) CZP 400 mg Q2W (n=342) 0% 0.8% 0.5% 1.7% 1.6% 0.9% 4.3% 21.0% 32.7% 44.5% 0.6% 3.4% 19.3% 37.4% 52.2% CZP Loading Dosea 44.5% 52.2% *p<0.05, **p<0.0001 versus placebo (not adjusted for multiplicity) aCZP 200 mg Q2W patients received loading dose of CZP 400 mg at Weeks 0, 2, and 4 Responder rates are the adjusted predicted probabilities based on logistic regression model with factors for treatment, region, study, prior biologic exposure (yes/no), and the interactions study*region and study*prior biologic exposure (yes/no) where missing data were imputed using multiple imputation (MCMC method) CZP, certolizumab pegol; MCMC, Markov chain Monte Carlo; PASI 90, ≥90% reduction in psoriasis area and severity index; Q2W, every 2 weeks Figure 6. Pooled DLQI Scores at Baseline and Week 16 and DLQI 0/1 Responder Rates at Week 16 Mean CfB: -2.4 11.0 13.4 Placebo (N=154) -9.1** 4.5 13.6 CZP 200 mg Q2Wa (N=347) -10.4** 4.1 14.5 CZP 400 mg Q2W (N=340) 8.3 Placebo (N=157) 42.7 CZP 200 mg Q2Wa (N=351) 47.1 CZP 400 mg Q2W (N=342) M e a n S c o re 20 15 10 5 0 A. DLQI Mean Scores and CfB BL Wk 16 R e sp o n d e r R a te ( % ) 100 80 60 40 20 0 B. DLQI 0/1 Responder Rates **p<0.0001 vs placebo based on adjusted least squares mean difference from an ANCOVA model with treatment group, region, study, prior biologic exposure (yes/no), and the interactions study*region and study*prior biologic exposure (yes/no) as factors and Baseline DLQI score as a covariate using LOCF imputation (p-values not adjusted for multiplicity); for DLQI 0/1 responder rates, missing data imputed based on NRI method (p-values not calculated) aCZP 200 mg Q2W patients received loading dose of CZP 400 mg at Weeks 0, 2, and 4 BL, Baseline; CfB, change from BL; CZP, certolizumab pegol; DLQI, Dermatology Life Quality Index; LOCF, last observation carried forward; NRI, nonresponder imputation; Q2W, every 2 weeks Pooled Safety • The safety profile for both CZP doses was consistent with the anti-TNF class in psoriasis; based on the known safety profile of CZP,6 no new safety signals were observed (Table 2) – The incidence of TEAEs was generally similar between CZP 400 mg Q2W and placebo groups, and was lower in the CZP 200 mg Q2W group versus placebo; TEAEs infrequently led to discontinuation • Serious TEAEs and serious infections and infestations were infrequent across treatment groups (CZP 400 mg Q2W: 4.7% and 0.6%, respectively; CZP 200 mg Q2W: 1.4% and 0%; placebo: 4.5% and 0%) (Table 2) – Two serious infections were reported in the CZP 400 mg Q2W group – hematoma infection and abdominal abscess in 1 patient following a bicycle accident, and pneumonia in 1 patient • No deaths were reported in any of the three studies through Week 16 (Table 2) Table 2. Treatment-Emergent Adverse Events (Safety Set) Placebo (N=157) CZP 200 mg Q2Wa (N=350) CZP 400 mg Q2W (N=342) TEAEs, n (%) All 97 (61.8) 197 (56.3) 217 (63.5) Serious 7 (4.5) 5 (1.4) 16 (4.7) Discontinuations due to TEAE, n (%) 0 4 (1.1) 4 (1.2) Deaths, n (%) 0 0 0 Frequent and other TEAEs of interest, n (%) Infections and infestations Latent tuberculosis Active tuberculosis Candida infections Oral fungal infection Fungal skin infection Nasopharyngitis Upper respiratory tract infection 53 (33.8) 0 0 0 0 0 19 (12.1) 11 (7.0) 108 (30.9) 0 0 1 (0.3) b 0 0 42 (12.0) 17 (4.9) 124 (36.3) 0 0 0 1 (0.3) 1 (0.3)c 43 (12.6) 23 (6.7) Serious infections 0 0 2 (0.6) d Non-melanoma skin cancer 0 0 1 (0.3) e Malignancy (excluding non-melanoma skin cancer) 0 0 0 Depression 0 2 (0.6) 2 (0.6) aCZP 200 mg Q2W patients received loading dose of CZP 400 mg at Weeks 0, 2, and 4 bVulvovaginal candidiasis cReported as fungal infection preferred term in the database dHematoma infection and abdominal abscess in 1 patient (bicycle accident), and pneumonia in 1 patient eBasal cell carcinoma Safety Set includes all randomized patients who received ≥1 dose of study medication CZP, certolizumab pegol; TEAE, treatment-emergent adverse event; Q2W, every 2 weeks Conclusions • In the phase 3 program, certolizumab pegol (CZP) 400 mg Q2W and CZP 200 mg Q2W were each associated with statistically significant, clinically meaningful improvements in moderate-to-severe chronic plaque psoriasis – Clinically meaningful differences in PASI 75 and PGA 0/1 responder rates versus placebo were observed as early as Week 4 – Greater improvement in quality of life as measured by CfB in DLQI and DLQI 0/1 responder rate was seen for both CZP dose groups compared with placebo at Week 16 – Responder rates were numerically greater for patients treated with CZP 400 mg Q2W versus 200 mg Q2W • In the phase 3 program, the safety profile for CZP was consistent with the anti-TNF class in psoriasis; based on the known safety profile of CZP, no new safety signals were observed – Serious TEAEs were infrequent across treatment groups References 1. Gottlieb et al. Oral presentation at: the 75th Annual Meeting of the American Academy of Dermatology; March 3-7, 2017; Orlando, FL. Abstract 5077 2. Reich et al. Poster presented at the 26th European Academy of Dermatology and Venerology Congress; September 13-17, 2017; Geneva, Switzerland 3. Lebwohl et al. Poster presentation at: 13th Annual Maui Derm for Dermatologists; March 20-24, 2017; Maui, HI 4. Augustin et al. Poster presented at the 26th European Academy of Dermatology and Venerology Congress; September 13-17, 2017; Geneva, Switzerland 5. Mariette et al. Ann Rheum Dis. 2017. doi: 10.1136/annrheumdis-2017-212196. [Epub ahead of print] 6. CIMZIA [package insert]. Smyrna, GA: UCB, Inc; 2016 Acknowledgements The studies were funded by Dermira, Inc.in collaboration with UCB, Inc. UCB is the regulatory sponsor of certolizumab pegol in psoriasis. Medical writing support for this presentation was provided by Prescott Medical Communications Group (Chicago, IL). All costs associated with the development of this presentation were funded by UCB. Author Disclosures AB: AbbVie; Aclaris; Allergan; Almirall; Amgen; Boehringer Ingelheim; Celgene; Dermavant; Dermira; Eli Lilly; Genentech/Roche; GSK; Janssen; LEO Pharma; Merck; Novartis; Pfizer; Purdue Pharma; Regeneron; Sandoz; Sanofi Genzyme; Sienna Pharmaceuticals; Sun Pharma; UCB; Valeant; Vidac. KR: AbbVie; Amgen; Biogen; Boehringer Ingelheim; Celgene; Centocor; Covagen; Eli Lilly; Forward Pharma; GSK; Janssen; LEO Pharma; Medac; Merck; Novartis; Ocean Pharma; Pfizer; Regeneron; Takeda; UCB; Xenoport. ML: AbbVie; Allergan; Amgen; Boehringer Ingelheim; Celgene; Eli Lilly; Janssen; LEO Pharma; Medimmune/AstraZeneca; Novartis; Pfizer; Sun Pharma; UCB; Valeant; Vidac. DB: Employee of Dermira. CA, LP, and RR: Employees of UCB. ABG: AbbVie; Allergan; Beiersdorf; Bristol-Myers Squibb; Celgene; Dermira; Eli Lilly; Incyte; Janssen; Novartis; Reddy Labs; Sun Pharma; UCB; Valeant.