Summer AAD Summer AAD Support provided by LEO Pharma A/S. Poster nº

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1 Support provided by LEO Pharma A/S Fixed combination calcipotriene plus betamethasone dipropionate aerosol foam provides improvement in quality of life and rapid relief of itch/itch-related sleep loss in psoriasis patients (PSO-FAST study) Craig Leonardi, Department of Dermatology, Saint Louis University School of Medicine, St Louis, MO, USA Jerry Bagel, Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ, USA Paul Yamauchi, Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA David Pariser, Eastern Virginia Medical School and Virginia Clinical Research, Inc, Norfolk, VA, USA Zhenyi Xu, LEO Pharma A/S, Ballerup, Denmark Anders Møller, LEO Pharma A/S, Ballerup, Denmark Martin Olesen, LEO Pharma A/S, Ballerup, Denmark Marie Louise Østerdal, LEO Pharma A/S, Ballerup, Denmark Linda Stein Gold, Henry Ford Health System, Detroit, MI, USA

2 Disclosures Dr Leonardi has been a consultant for LEO Pharma, AbbVie, Amgen, Dermira, Eli Lilly, Janssen, Sandoz, UCB, Pfizer, received honoraria from Abbvie, Amgen, Dermira, Eli Lilly, Sandoz, UCB, Pfizer, Celgene, Novartis, and has participated in speakers bureaus for AbbVie and Celgene Dr Bagel has been a consultant, has participated in speakers bureaus, has been an investigator for LEO Pharma, AbbVie, Janssen, Celgene, Novartis, and has been a consultant and investigator for Eli Lilly Dr Yamauchi has received grants from LEO Pharma, Amgen, Celgene, Galderma USA, Janssen-Ortho Inc, Lilly ICOS LLC, Pfizer Inc., honoraria from LEO Pharma, AbbVie, Amgen, Baxter, Galderma USA, Janssen-Ortho Inc, Lilly ICOS LLC, Novartis Pharmaceuticals Corp., Pfizer Inc. Dr Pariser has received grants from LEO Pharma and has no other relevant disclosures Dr Xu, Mr Møller and Ms Østerdal are employees of LEO Pharma Dr Olesen was an employee of LEO Pharma at the time of this trial Dr Stein Gold has been a consultant for LEO Pharma, Pfizer, Novartis, Lilly, Galderma, Valeant, Taro, Activis, Allergan, has received honoraria from LEO Pharma, Pfizer, Novartis, Lilly, Galderma, Valeant, Taro, Activis, Allergan, and has participated in speakers bureaus for LEO Pharma, Pfizer, Novartis, Lilly, Galderma, Valeant, Taro, Activis, Allergan

3 Introduction and methods Introduction: The large, Phase III, double-blind PSO-FAST ( in PSOriasis vulgaris, a Four-week, vehicle-controlled, efficacy And Safety Trial) study confirmed the efficacy and safety of fixed combination in patients with psoriasis vulgaris (plaque psoriasis) 53.3% of patients using and 4.8% of patients using vehicle were clear/almost clear with a two-step improvement at Week 4, according to the PGA Methods: Patients with mild-to-severe disease were enrolled from 27 US centers and randomized 3:1 to once-daily fixed combination or vehicle Patients treated all plaques, excluding those on the head, once-daily for up to 4 weeks (maximum of 9 g per week) Key inclusion criteria Patients (age 18 years) with at least mild psoriasis (according to PGA) of the trunk and/or limbs 6 month duration of disease Amenable to topical therapy 2 3% of body surface area affected (trunk and/or limbs) mpasi score of 2 on the trunk and/or limbs BD, betamethasone dipropionate.64%; Cal, calcipotriene.5%; mpasi, modified (excluding the head, which was not treated) psoriasis area and severity index; PGA, physician s global assessment of disease severity PSO-FAST trial identifier: NCT Treatment success was defined as clear/almost clear with a two-step improvement.

4 Study assessments HRQoL DLQI questionnaires were completed at baseline and Weeks 1, 2, and 4 (range 3)* EQ-5D-5L questionnaires were completed at baseline and Week 4 (utility index range 1; VAS range 1) Post hoc assessments Itch Proportion of patients with no impairment in DLQI (score /1) at Week 4 Proportion of patients who had a minimal clinically important difference (MCID; 5-point improvement in patients with baseline DLQI 5) in DLQI score by Week 4 Proportion of patients who had no impairment (score of 1) on the EQ-5D-5L dimensions: mobility, self-care, usual activities, pain/discomfort, or anxiety/depression at Week 4 Patients assessed itch and itch-related sleep loss at baseline, on Days 3 and 5 (recorded in patient diaries), and at visits at Weeks 1, 2 and 4, according to a VAS (range 1) Patients reported: Maximal itch intensity over the 24-hour period prior to the assessment Itch-related sleep loss during the night prior to the assessment Post hoc assessments Itch responders, defined as patients with baseline itch/itch-related sleep loss who reported a 7% reduction during the treatment period Objective: to compare treatment with and vehicle by determining the change in HRQoL, itch and itch-related sleep loss from baseline to Week 4 DLQI, dermatology life-quality index; HRQoL, health-related quality of life; VAS, visual analog scale; *DLQI scores: = no impairment; 3 = highest possible impairment. EQ-5D-5L utility score: 1 = perfect health; EQ VAS: 1 = best health imaginable. Itch VAS: 1 = worse.

5 Patient demographics and baseline characteristics Characteristic (n=323) Randomized patients (n=426) (n=13) Median age, years (range) 52 (18 87) 46 (19 79) Males, n (%) 24 (63.2) 49 (47.6) Race, n (%) White Black or African American Other 276 (85.4) 24 (7.4) 23 (7.1) 9 (87.4) 6 (5.8) 7 (6.8) Mean body surface area, % (±SD) 7.4 (±6.4) 8. (±7.) PGA, n (%) Mild Moderate Severe 5 (15.5) 244 (75.5) 29 (9.) 15 (14.6) 75 (72.8) 13 (12.6) Mean mpasi score (range) 7.4 (2 37) 7.9 (2 47) Mean DLQI score Mean EQ-5D-5L utility index score Mean itch VAS score Baseline mean DLQI scores were approximately 1 for both treatment groups, indicating a substantial impact on the patient s life 1 SD, standard deviation 1. Finlay AY. Br J Dermatol 25;152:

6 DLQI scores by visit and proportion of patients with no impairment (score of /1) * DLQI score (95% CI) Mean vs vehicle Difference (95% CI) P-value Change in DLQI (Week 4): 7.1 vs ( 3.7 to 1.9) < Propor rtion of patients with a DLQI score of or 1 (%) Time (weeks) Time (weeks) At Weeks 1, 2 and 4, there were statistically significantly greater mean improvements from baseline in DLQI scores in patients treated with versus vehicle. Improvements were seen throughout the study with both treatments By Week 4, statistically significantly more patients using than those using vehicle reported no impact of psoriasis on their lives (P<.1) ANCOVA, analysis of covariance; CI, confidence interval. P-values calculated using ANCOVA, adjusted for pooled centers and baseline score. *DLQI scores: 1 = no effect at all on patient s life; 2 5 = small effect on patient s life; 6 1 = moderate effect on patient s life; 11 2 = very large effect on patient s life; 21 3 = extremely large effect on patient s life.

7 Proportions of patients with a 5-point improvement in DLQI and with no impairment in individual EQ-5D-5L dimensions (score of 1)* Propor rtion of patients with a 5-point improvement in DLQI (%) Proportio on of patients with no impair rment in individual EQ-5D- -5L dimensions (%) Time (weeks) 243/322 (75%) patients treated with had DLQI scores 5 at baseline; MCID was achieved by 81% of these patients at Week 4 vs vehicle (Improvements at Week 4) Difference (95% CI) P-value EQ-5D-5L utility index:.8 vs.4.4 (.1 to.7).5 EQ VAS: 5.1 vs (1.4 to 7.1) Baseline Week 4 Baseline Week 4 Baseline Mobility Self care Usual activities Pain/ discomfort Anxiety/ depression Impact on HRQoL at baseline was particularly driven by pain/discomfort and anxiety/depression. A statistically significantly greater proportion of patients reported no pain/discomfort with versus vehicle. By Week 4, there was an improvement in usual activities and anxiety/depression in both treatment groups Week 4 Baseline Week 4 Baseline Week 4 P-value calculated using ANCOVA, adjusted for pooled centers and baseline score P-value calculated using the Cochran Mantel Haenszel method, adjusted for pooled centers. *EQ-5D-5L 5-point scale: 1 = no problems; 2 = slight problems; 3 = moderate problems; 4 = severe problems; 5 = extreme problems. DLQI scores: 1 = no effect at all on patient s life; 2 5 = small effect on patient s life; 6 1 = moderate effect on patient s life; 11 2 = very large effect on patient s life; 21 3 = extremely large effect on patient s life.

8 Itch/itch-related sleep loss by visit Mean itc ch VAS score (95% CI) * * * P=.1 * * Mean it tch-related sleep loss VA AS score (95% CI) * * P=.9 P=.4 * * Day Time Week Day Time Week Improvements from baseline in itch VAS score were rapid, being reported by the earliest assessment (Day 3). The improvements were statistically significantly greater with than vehicle at all time points Itch-related sleep loss was also statistically significantly improved with versus vehicle at all time points P-values calculated using ANCOVA, adjusted for pooled centers and baseline score

9 Itch/itch-related sleep loss responders by visit 37% of patients (11/299) in the group were classified as itch responders by Day 3. The proportion steadily increased over the study period, reaching 84% (248/297) by the end of treatment 36% of patients (87/245) using were classified as itch-related sleep loss responders by Day 3, which increased to 71% (172/243) by the end of treatment of patients achieving duction in itch (%) Proportion 7% red P= Proportion of patients achieving 7% reduction in itch-related sleep loss P=.2 P= P= P= Day Time Week Day Time Week A statistically significantly greater proportion of patients were itch responders in the Cal/BD group, compared with vehicle, at all time points Statistically significantly more patients in the Cal/BD aerosol foam group were itch-related sleep loss responders than in the vehicle group at all time points P-values calculated using the Cochran Mantel Haenszel method, adjusted for pooled centers Responders defined as those with 7% reduction in itch/itch-related sleep loss.

10 Summary and conclusions improved the HRQoL of patients in the PSO-FAST study (according to DLQI/EQ-5D-5L) Clinically meaningful improvements observed by Week 4 ( 5-point change in DLQI score in 81% of patients with baseline scores 5) Almost 5% of all patients treated with reported no impairment (DLQI /1) by end of treatment Itch, a common and troublesome symptom of psoriasis that often severely impacts patient HRQoL, was rapidly relieved in patients treated with Cal/BD aerosol foam Most patients achieved itch response (ie 7% reduction in itch) by Day 5 of treatment Itch-related sleep loss response was also rapid, with most patients achieving responder status by Week 1 In summary, the improvement in HRQoL and the rapid alleviation of itch, in addition to the efficacy and favorable tolerability profile of the, may lead to better patient adherence and offer these patients with psoriasis vulgaris a better treatment experience