REFERENCES 1. Zuberbier T, et al. Allergy. 2014;69:868–87; 2. Saini S, et al. J Invest Dermatol. 2015;135:67–75; 3. Maurer M, et al. N Engl J Med. 2013;368:924–35; 4. Kaplan A, et al. J Allergy Clin Immunol. 2013;132:101–9; 5. Mathias SD, et al. Ann Allergy Asthma Immunol. 2010;105:42–8; 6. Bretz F, et al. Stat Med. 2009;28:586–604. ACKNOWLEDGMENTS All authors participated in the development of the poster and approved the final poster for presentation. Medical writing in the development of this poster was provided by Novartis Ireland Ltd. Editorial assistance was provided by Jessica Donaldson of Fishawack Communications Ltd, Oxford, UK. This poster was previously presented at the American Academy of Dermatology Annual Meeting, March 3–7, 2017, Orlando, FL, USA, and at the 5th Annual Maui Derm NP+PA Summer Meeting, June 14–17, 2017, Colorado Springs, CO, USA. FUNDING This study was funded by Novartis Pharmaceuticals, East Hanover, NJ, USA. DISCLOSURES MH, H-SP, AI, Y-MY, T-BK, AY, JR, J-HL, and AF have nothing to disclose. SK is an employee of Novartis Pharmaceuticals Corporation. INTRODUCTION • Chronic idiopathic/spontaneous urticaria (CIU/CSU) is a prevalent skin condition, characterized by the spontaneous appearance of wheals (hives) or angioedema, or both, that persist for ≥6 weeks1 • For patients who do not respond to H 1 antihistamines (H1AH) – the mainstay of treatment for CIU/CSU1 – the humanized monoclonal anti-IgE antibody omalizumab has been demonstrated to be an effective treatment option2–4 • Three placebo-controlled, randomized Phase 3 studies (ASTERIA I [NCT01287117], ASTERIA II [NCT01292473], and GLACIAL [NCT01264939]) have established the efficacy and safety of omalizumab in a predominately Caucasian population2–4 Study outcome measures • The primary outcome was change from baseline in ISS7. The primary analysis time point was at Week 12 • Secondary outcomes evaluated at Week 12 were the following: − Change from baseline in UAS7 − Change from baseline in HSS7 − Change from baseline in the DLQI score − Percentage of ISS7 MID responders − Proportion of patients achieving UAS7 ≤6 or UAS7 =0 • Safety was assessed through the summary of adverse events (AEs) Statistical analysis • A linear mixed model with repeated measures (country stratum, treatment group, week, and treatment-by-week interaction included as fixed effects, patient as a random effect, and baseline score as a covariate) was used to estimate treatment differences for the primary variable and selected secondary variables, including change from baseline to Week 12 in UAS7 and HSS7 • Treatment comparisons for proportions of patients at Week 12 with ISS7 MID response, UAS7 ≤6, and UAS7 =0 were performed using a logistic regression model (country stratum and treatment group as factors, and baseline value as a covariate) • A gate-keeping procedure was used to adjust the P-values of the two comparisons.6 The graphic approach of sequentially rejective, multiple testing procedures was used to illustrate the testing strategy of the two families of hypotheses6 RESULTS Baseline characteristics • Most disease characteristics were well balanced across treatment arms (Table 1) − A slight imbalance in duration of CIU/CSU was observed OBJECTIVE • The objective of the POLARIS study was to evaluate the efficacy and safety of omalizumab in an Eastern Asian population with CIU/CSU who remain symptomatic despite H1AH therapy METHODS Study design • POLARIS was a 26-week, randomized, double-blind, placebo-controlled, parallel-group multicenter Phase 3 study, conducted in 41 sites (26 centers in Japan and 15 in Korea) • The study comprised a 2-week screening period, 12-week randomized- treatment period, and 12-week follow-up (conducted between December 2014 and December 2015) (Figure 1) • Patients were randomized (1:1:1) to omalizumab 150 mg, 300 mg or placebo, administered subcutaneously every 4 weeks for a total of three doses CONCLUSIONS • POLARIS represents the first Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial of omalizumab for CIU/CSU in an Eastern Asian population • The results demonstrate that omalizumab treatment results in significant clinical benefits with no new safety concerns in patients with H1AH-refractory CIU/CSU in Japan and Korea • These findings suggest that ethnic differences do not affect CIU/CSU treatment outcomes with omalizumab Screening (2 weeks) −2 BaselineWeek Omalizumab or placebo 4 8 12 16 20 24 Treatment (12 weeks) Follow-up (12 weeks) Screening Primary analysis time point Completed treatment Completed study Omalizumab 300 mg (n=73) Omalizumab 150 mg (n=71) Placebo (n=74) Background treatment, H1AH (approved dose) +diphenhydramine* as needed Additional H1AH (optional) Figure 1. POLARIS study design *Up to 80 mg/day (10 mg tablet in Japan) or 75 mg/day (25 mg tablet in Korea). H1AH, H 1 antihistamines. 100 90 80 70 60 50 40 30 20 10 0 P ro p o rt io n o f p a ti e n ts ( % ) OMA 300 mg 87.7 OMA 150 mg 68.6 Placebo 55.4 1.84 (0.92, 3.69); P=NS* 5.51 (2.36, 12.86); P<0.001 Figure 5. Proportion of patients with ISS7 MID response at Week 12 Data for odds ratio (95% CI) are presented. ISS7 MID response defined as reduction from baseline in ISS7 ≥5 points.5 P-values are unadjusted and represent differences between the indicated active treatment groups and placebo. *Adjusted P-value was not <0.05. ISS7, itch severity score over 7 days; MID, minimally important difference; NS, non significant; OMA, omalizumab. M e a n c h a n g e f ro m b a s e li n e Omalizumab or placebo administered * 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 (Week) 0 −5 −10 −15 −20 −25 Omalizumab 300 mg Omalizumab 150 mg Placebo Figure 3. Change from baseline in UAS7 *LS mean values for change from baseline to Week 12 in UAS7 were –22.44, –18.79, and –13.90 with omalizumab 300 mg, 150 mg, and placebo, respectively. LS mean difference for treatment (95% CI): −8.55 (−12.05, −5.05), unadjusted P<0.001 (adjusted P<0.05) and −4.89 (−8.45, −1.34), unadjusted P=0.007 (adjusted P<0.05) for omalizumab 300 mg and 150 mg groups versus placebo, respectively. UAS7 was defined according to previous studies for omalizumab.5 CI, confidence interval; LS, least squares; UAS7, urticaria activity score over 7 days. 70 60 50 40 30 20 10 0 P ro p o rt io n o f p a ti e n ts ( % ) Week 4 Week 8 Week 12 P<0.001 P=0.002 Omalizumab 300 mg Omalizumab 150 mg Placebo Proportion achieving UAS7 ≤6 40 35 30 25 20 15 10 5 0 P ro p o rt io n o f p a ti e n ts ( % ) Week 4 Week 8 Week 12 P<0.001 P=0.013* Proportion achieving UAS7 =0 Omalizumab 300 mg Omalizumab 150 mg Placebo Figure 6. Proportion of responders by Week 12 P-values are unadjusted and represent differences between the indicated active treatment groups and placebo. *Adjusted P-value was not <0.05. UAS7, urticaria activity score over 7 days. 100 90 80 70 60 50 40 30 20 10 0 C u m u la ti ve p ro p o rt io n o f p a ti e n ts w it h o u t e ve n t (% ) Week 0 Week 4 Week 8 Week 12 Censor flags Omalizumab 300 mg Omalizumab 150 mg Placebo Survival curves Omalizumab 300 mg Omalizumab 150 mg Placebo Study week Figure 7. Time to UAS7 ≤6 response UAS7, urticaria activity score over 7 days. • Patients treated with omalizumab experienced greater mean decreases in UAS7 at all time points from Week 1 through Week 12, compared with patients in the placebo group (Figure 3) − LS mean difference for omalizumab 300 mg and omalizumab 150 mg were P<0.001 and P=0.007 versus placebo, respectively • During posttreatment follow-up, mean UAS7 values were increased in the omalizumab groups but did not revert to pretreatment levels (Figure 3) • At Week 12, a statistically significant improvement in HSS7 was observed in both omalizumab groups compared with placebo (Figure 4) • A statistically significant improvement was also observed in the overall DLQI score in the omalizumab 300 mg group compared with placebo (P<0.001) (Figure 4) − The improvement in DLQI score observed with omalizumab 150 mg did not achieve statistical significance (adjusted P-value >0.05) M e a n c h a n g e f ro m b a s e li n e Omalizumab or placebo administered * 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 (Week) 0 −2 −4 −6 −8 −10 −12 Omalizumab 300 mg Omalizumab 150 mg Placebo Figure 2. Change from baseline in ISS7 *Change from baseline in ISS7 was the primary outcome and Week 12 was the primary analysis time point; ISS7 LS mean values at Week 12 were −10.22, −8.80, and −6.51 with omalizumab 300 mg, 150 mg, and placebo, respectively. LS mean difference for treatment (95% CI): −3.70 (−5.31, −2.10), unadjusted P<0.001 (adjusted P<0.05) and −2.29 (−3.92, −0.65), unadjusted P=0.006 (adjusted P<0.05) for omalizumab 300 mg and 150 mg groups versus placebo, respectively. CI, confidence interval; ISS7, itch severity score over 7 days; LS, least squares. Study population • The study population consisted of males and females, aged 12–75 years, with a diagnosis of CIU/CSU for ≥6 months that was refractory to conventional H1AH at the time of randomization • Eligible patients had: − Itch and hives for ≥8 consecutive weeks at any time prior to enrollment despite current H1AH treatment during this time period − Urticaria activity score over 7 days (UAS7) ≥16 and itch component of UAS7 (range: 0–21) ≥8 during 7 days prior to randomization (Day 1) − In-clinic UAS ≥4 on at least one of the screening visits (Day −14, Day −7, or Day 1) − Been on an approved dose of an H1AH for CIU/CSU for ≥3 consecutive days immediately prior to the Day −14 screening visit and must have documented current use on the day of the initial screening visit • Subjects recorded a daily symptom diary, reporting number of hives and intensity of pruritus (scale 0 [none] to 3 [intense/severe]) • Average daily scores were totaled each week to provide itch severity score over 7 days (ISS7; scale 0–21), number of hives score over 7 days (HSS7; scale 0–21), and weekly composite outcome (UAS7; scale 0–42). ISS7 minimally important difference (MID) response defined as reduction from baseline in ISS7 ≥5 points.5 The Dermatology Life Quality Index (DLQI) assessment was completed (scale 0–30), where lower scores represent better quality of life Efficacy Primary outcome • Compared with baseline, mean ISS7 was decreased and remained below baseline in all treatment groups during the 24-week study period (Figure 2) − Greater ISS7 change from baseline was observed in the omalizumab 300 mg group versus omalizumab 150 mg from Weeks 4 to 12, and was sustained up to Week 20 in the follow-up • Patients treated with omalizumab experienced greater mean decreases in ISS7 at all time points from Week 1 through Week 12, compared with patients in the placebo group (Figure 2) − Least squares (LS) mean difference for omalizumab 300 mg and omalizumab 150 mg were P<0.001 and P=0.006 versus placebo, respectively • During post-treatment follow-up, mean ISS7 values were increased in the omalizumab groups but did not revert to pretreatment levels (Figure 2) Secondary outcomes • Compared with baseline, mean UAS7 was decreased and remained below baseline in all treatment groups during the 24-week study period (Figure 3) − Greater UAS7 change from baseline was observed in the omalizumab 300 mg group versus omalizumab 150 mg from Weeks 4 to 12, and was sustained up to Week 20 in the follow-up • At Week 12, in the omalizumab 300 mg group the proportion of patients with ISS7 MID response was significantly greater compared with placebo (Figure 5) − Results for omalizumab 150 mg were not significantly different compared with placebo 0 –2 –4 –6 –8 –10 –12 –14 C h a n g e f ro m b a s e li n e –2.63 (–4.75, –0.50)† OMA 300 mg OMA 150 mg Placebo –12.17 –10.04 –7.41 –4.76 (–6.84, –2.67)* –1.9 (–3.36, –0.44)†,‡ –3.1 (–4.59, –1.69)* 0 –2 –4 –6 –8 –10 C h a n g e f ro m b a s e li n e OMA 300 mg OMA 150 mg Placebo –8.4 –7.2 –5.3 Change from baseline in HSS7 Change from baseline in overall DLQI score Figure 4. Efficacy outcomes at Week 12 Data for LS mean treatment difference (95% CI) are presented. *Unadjusted P<0.001; †unadjusted P<0.05; ‡adjusted P-value was not <0.05. CI, confidence interval; DLQI, Dermatology Life Quality Index; LS, least squares; OMA, omalizumab. Table 1. Demographics and baseline characteristics Omalizumab 300 mg (n=73) Omalizumab 150 mg (n=71)* Placebo (n=74) Age, years 44.6 (14.9) 43.6 (12.2) 42.5 (14.3) Age group <18 years, n (%) 2 (2.7) 1 (1.4) 1 (1.4) Female, n (%) 40 (54.8) 43 (60.6) 48 (64.9) Ethnicity, n (%) Japanese 35 (47.9) 34 (47.9) 36 (48.6) Korean 38 (52.1) 37 (52.1) 38 (51.4) Weight, kg 65.3 (13.3) 65.0 (14.1) 63.0 (13.4) Body mass index, kg/m2 24.4 (3.9) 24.3 (4.8) 23.3 (4.0) Duration of CIU/CSU, years 3.6 (4.0) 5.1 (6.2) 4.7 (6.2) Previous number of CIU/CSU medications 6.8 (5.2) 6.3 (5.0) 7.4 (5.3) UAS7 31.8 (7.1) 29.6 (7.4) 30.1 (6.5) ISS7 14.6 (3.7) 13.2 (4.0) 13.7 (3.3) Overall DLQI score 12.0 (6.5) 11.0 (5.9) 10.9 (6.4) Data are mean (SD) for the randomized set, unless otherwise indicated. *One subject randomized to omalizumab 150 mg had UAS7 and ISS7 of 4.0 and 2.5, respectively. This patient did not meet the inclusion criterion and was excluded from the FAS. CIU/CSU, chronic idiopathic/spontaneous urticaria; DLQI, Dermatology Life Quality Index; FAS, full analysis set; ISS7, itch severity score over 7 days; UAS7, urticaria activity score over 7 days; SD, standard deviation. Table 2. Treatment-emergent AEs during the 24-week study period Adverse events Omalizumab 300 mg (n=73) Omalizumab 150 mg (n=70) Placebo (n=74) Any AE 40 (54.8) 41 (57.7) 41 (55.4) Any AE leading to discontinuation of study drug 0 1* (1.4) 0 Any serious AE 3 (4.1) 3 (4.2) 0 Death 0 0 0 Any AE possibly related to study drug 7 (9.6) 6 (8.5) 9 (12.2) Any severe AE 1 (1.4) 0 0 Most frequent AEs occurring in ≥2% of subjects Nasopharyngitis 9 (12.3) 7 (9.9) 12 (16.2) Eczema 5 (6.8) 3 (4.2) 2 (2.7) CIU/CSU 3 (4.1) 1 (1.4) 1 (1.4) Headache 3 (4.1) 3 (4.2) 5 (6.8) Pharyngitis 3 (4.1) 3 (4.2) 0 Data for the safety set are presented as number of patients (%). *Any AE leading to discontinuation of study drug was reported in the omalizumab 150 mg group: pharyngeal edema (Day 1 – Day 4); suspected; mild. This AE was adjudicated as nonanaphylaxis by ARC because it did not meet Sampson criteria (ie, only one organ system involved). AE, adverse event; ARC, Adjudication Review Committee; CIU/CSU, chronic idiopathic/spontaneous urticaria. Safety and tolerability • Overall incidence of AEs was similar across treatment arms (54.8%, 57.7%, and 55.4% of subjects with omalizumab 300 mg, 150 mg, and placebo, respectively) (Table 2) − Nasopharyngitis was the most frequently reported AE with all treatments − CIU/CSU events reported in the omalizumab 300 mg arm were reported in the follow-up epoch and were not deemed to be related to study medication − No exacerbation of CIU/CSU, as indicated by UAS7 response, was observed relative to baseline • At Week 4, a higher proportion of responders (ie, achieving UAS7 ≤6 or =0) was observed in the omalizumab 300 mg and 150 mg groups, compared with placebo (Figure 6) • The difference in the proportions of responders in the active treatment and placebo groups was increased at the later assessments and were greater with omalizumab 300 mg than with omalizumab 150 mg (Figure 6) • The median time to achieve UAS7 ≤6 response was (Figure 7): − 7 weeks in the omalizumab 300 mg group − 9 weeks in the omalizumab 150 mg group Scan this QR code Visit the web at: http://novartis.medicalcongressposters.com/Default.aspx?doc=8b028 Mobile Friendly e-Prints 3 ways to instantly download an electronic copy of this poster to your mobile device or e-mail a copy to your computer or tablet Text Message (SMS) Text: Q8b028 to: 8NOVA (86682) US Only +18324604729 North, Central and South Americas; Caribbean; China +447860024038 UK, Europe & Russia +46737494608 Sweden, Europe Standard data or message rates may apply. EFFICACY AND SAFETY OF OMALIZUMAB IN JAPANESE AND KOREAN PATIENTS WITH CHRONIC IDIOPATHIC/SPONTANEOUS URTICARIA (CIU/CSU): RESULTS FROM THE PHASE 3 POLARIS STUDY Michihiro Hide,1 Hae-Sim Park,2 Atsuyuki Igarashi,3 Young-Min Ye,2 Tae-Bum Kim,4 Akiko Yagami,5 JooYoung Roh,6 Jae-Hyun Lee,7 Atsushi Fukunaga,8 Sam Khalil,9 on behalf of the POLARIS Study Group 1Department of Dermatology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; 2Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea; 3Department of Dermatology, NTT Medical Center Tokyo, Tokyo, Japan; 4Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 5Department of Allergology, Fujita Health University Second Educational Hospital, Nagoya, Japan; 6Department of Dermatology, Gachon University Gil Medical Center, Incheon, Korea; 7Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea; 8Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan; 9Novartis Pharma AG, Basel, Switzerland Presented at the Fall Clinical Dermatology Conference, October 12–15, 2017, Las Vegas, NV, USA