First Real-World Insights on Apremilast Therapy for Patients With Plaque Psoriasis From the LAPIS-PSO Study: An Interim Analysis

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1 5137 First Real-World Insights on Apremilast Therapy for Patients With Plaque Psoriasis From the Study: An Interim Analysis Kristian Reich, MD 1 ; Stefanie Bomas, MD 2 ; Bernhard Korge, MD 3 ; Maria Manasterski, MD 4 ; Uwe Schwichtenberg, MD 5 ; Markus Altmann, PhD 6 ; Katrin Lorenz-Baath, PhD 6 ; Kathrin Groegel, PhD 6 1 SCIderm Research Institute and Dermatologikum Hamburg, Hamburg, Germany; 2 Praxis Dr. med. S. Rotterdam, Gelsenkirchen-Feldmark, Germany; 3 Priv. Doz. Dr. med. Korge, Düren, Germany; 4 Hautarztpraxis Manasterski und Dues, Berlin, Germany; 5 Derma Nord Hautarztpraxen Dr. med. Schwichtenberg, Bremen, Germany; 6 Celgene GmbH, München, Germany Presented at: the 75th Annual Meeting of the American Academy of Dermatology; March 3 7, 2017; Orlando FL. This study was sponsored by Celgene Corporation.

2 Acknowledgments, Correspondence, and Disclosures Acknowledgments The authors acknowledge financial support for this study from Celgene Corporation. The authors received editorial assistance from Peloton Advantage, LLC (Kathy Covino, PhD), sponsored by Celgene Corporation. Correspondence Kristian Reich Disclosures KR: AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celgene Corporation, Centocor, Covagen, Eli Lilly, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Medac, Merck Sharp & Dohme Corp, Novartis, Ocean Pharma, Pfizer (Wyeth), Regeneron, Takeda, UCB Pharma, and XenoPort honoraria as a consultant and/or advisory board member and/or acted as a paid speaker and/or participated in clinical trials. SB: No conflicts or potential conflicts of interest to disclose. BK: No conflicts or potential conflicts of interest to disclose. MM: AbbVie, Janssen, and Novartis paid consultant or study investigator. US: AbbVie Deutschland Gmbh, Almirall Hermal GmbH, Astellas Pharma GmbH, Beiersdorf Derma Medical GmbH, Celgene GmbH, Janssen Cilag GmbH, Johnsons & Johnson GmbH, LEO Pharma GmbH, L Oréal GmbH, MEDA Pharma GmbH, Merz Pharmaceuticals GmbH, MSD SHARP & DOHME GmbH, Novartis Pharma GmbH, Pfizer GmbH, and Medical Project Design GmbH paid speaker, advisory board member, investigator, and/or stockholder. MA, KL-B & KG: Celgene Corporation employment.

3 Introduction This national, multicenter, prospective, noninterventional study is assessing long-term treatment with apremilast in patients with plaque psoriasis in Germany (; NCT ). This study aims to determine patients quality of life and satisfaction with apremilast treatment, as well as the clinical efficacy and safety/tolerability of apremilast in a real-world setting of patients who have previously received conventional systemic therapy. The interim analysis from the study is presented here.

4 Study Design: VISIT 0 BL VISIT 1 Optional VISIT 2 VISIT 3 VISIT 4 VISIT 5 End of Observation Primary End Point Time [ months] Primary end point: Percentage of patients achieving DLQI score 5 or improvement from BL in DLQI score by 5 points at Visit 2 Secondary end points: Efficacy, patient satisfaction, and tolerability Patients Moderate to severe plaque psoriasis (N=500) Indication and inclusion according to apremilast SmPc label Patients previously treated with biologics are not observed No strict visit schedule is performed; visits are timed according to clinical practice BL=baseline; DLQI=Dermatology Life Quality Index.

5 Study Population The present interim analysis included 111 patients from 39 study centers who had completed Visit 2 and received 4 months of treatment with apremilast 30 mg BID (APR). 32 patients were excluded from the FAS because of DLQI <5 at inclusion. 8 patients were excluded from the FAS because of missing DLQI data at BL and/or Visit 2. Reasons for drop outs were lack of efficacy (n=6; 40%), AEs (n=7; 47%), others (n=2; 13%). Visit Patients n Safety Population* Patients Dropped Out n Patients n Full Analysis Set Patients Dropped Out n Visit 0 (BL) Visit 1 (optional; 1 month after BL visit) Visit 2 ( 4 months after BL visit) *Safety population includes all patients who received 1 dose of APR and fulfilled inclusion criteria. AEs=adverse events; FAS=full analysis set.

6 Patient Demographics Characteristic Safety Population n=108 Full Analysis Set n=73 Male, % Age at inclusion, mean (SD), years 52.9 (13.40) 50.9 (13.19) BMI, mean (SD), kg/m (5.29) 28.0 (5.48) BSA, mean (SD), % NR 22.9 (18.36) Scalp involvement, % Nail involvement, % Palmoplantar involvement, % Erythrodermic psoriasis, n (%) 1 (1.0) 0 Guttate psoriasis, n (%) 3 (3.0) 2 (2.9) Inverse psoriasis, n (%) 15 (14.9) 7 (10.1) BMI=body mass index; BSA=body surface area; NR=not reported.

7 Interim Analysis: DLQI Response Rapid onset was demonstrated by a mean DLQI reduction of 6 points and a 65% response rate as early as 1 month after BL. Average DLQI improvement further increased from Visit 1 to Visit 2. The primary end point was reached by 64% of patients, with mean DLQI improvement of 8 points at 4 months of treatment. Visit 1 ( 1 Month After BL) n=65 Visit 2 ( 4 Months After BL) n=64 Achievement of DLQI score 5, n (%) 26 (40) 31 (48) DLQI improvement from BL of 5, n (%) 37 (57) 37 (58) Achievement of DLQI score 5 or DLQI improvement from BL of 5, n (%) 42 (65) 41 (64) Change from BL, mean (SD) 6 (5.99) 8 (7.30) Mean (SD) DLQI score at BL was 14.6 (6.31).

8 Interim Analysis: PGA and PaGA Response A high degree of correlation existed between physician and patient assessment as analyzed through cross-tables (84.6% at Visit 1 and 90.8% at Visit 2). Achievement of PGA or PaGA Score of 0 or 1, % PGA and PaGA Response* 27 0 n/n = 2/73 10/67 18/66 3/72 6/65 20/65 PGA Response Visit 0 Visit 1 ( 1 month after BL visit) Visit 2 ( 4 months after BL visit) *The PGA and PaGA are 5-point scales ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe). PaGA=Patient Global Assessment; PGA=Physician Global Assessment PaGA Response

9 Interim Analysis: Response of Pruritus and Skin Pain Mean change from BL in pruritus and skin pain VAS scores improved from Visit 1 to Visit 2 ( 4 months). Mean (SD) change in pruritus VAS score, mm Mean (SD) change in skin pain VAS score, mm Visit 1 ( 1 Month After BL) n=64 Mean (SD) BL puritus VAS score = 57.8 mm (26.84) (N=73) Mean (SD) BL skin pain VAS score = 38.6 mm (27.88) (N=73) Visit 2 ( 4 Months After BL) n= (28.14) 27.5 (33.05) 11.9 (24.59) 20.7 (31.54) VAS=visual analog scale (0 100 mm).

10 Interim Analysis: Efficacy on Nail Psoriasis: Target Nail Psoriasis Severity Index (Target-NAPSI) Relative improvement in NAPSI score in the target nail was 54% at Visit 2 (mean [SD] absolute change: 2.4 [1.85 ] from BL 4.2 [2.25]). NAPSI-50 Response, % NAPSI-50 Response n = 7/30 20/30 Visit 1 Visit 2 ( 1 Month After BL) ( 4 Months After BL) NAPSI=Nail Psoriasis Severity Index; NAPSI-50=a 50% reduction from BL in NAPSI score. 67

11 Interim Analysis: Efficacy on Scalp Involvement At BL, 64% of patients had a Scalp Physician Global Assessment (ScPGA) score 3. At Visit 2, ScPGA score of 0 (clear) or 1 (almost clear) was achieved by 29 of 57 patients (51%) with scalp psoriasis. ScPGA Response Patients (n) n = Visit 0 (BL) Visit 1 ( 1 Month After BL) Visit 2 ( 4 Months After BL) clear Clear (ScPGA=0) almost clear Almost clear (ScPGA=1) mild Mild (ScPGA=2) moderate Moderate (ScPGA=3) severe Severe (ScPGA=4)

12 Interim Analysis: Palmoplantar Psoriasis 80% (8/10) of the patients with Palmoplantar Psoriasis Physician s Global Assessment (PPPGA) score 2 at BL reached a PPPGA score of 0 (clear) or 1 (almost clear) after 4 months. Patients* (n) PPPGA Response n = Visit 0 Visit 1 Visit 2 (BL) ( 1 Month After BL) ( 4 Months After BL) *Patients with PPPGA score 1 at BL. 3 clear Clear (PPPGA=0) almost clear Almost clear (PPPGA=1) mild Mild (PPPGA=2) moderate Moderate (PPPGA=3) severe Severe (PPPGA=4)

13 Interim Analysis: Patient Preference After 4 Months The patient preference questionnaire revealed a very high degree of patient satisfaction at 4 months of treatment, with 88% of patients stating that they preferred APR treatment over their previous therapy. I fully agree I agree I disagree I fully disagree Patients After 4 Months more More effectice effective more More convenient in application less Less side side effects effects better Better tolerable tolerability is Prefer preferred the actual over previous therapy therapy Q1: In comparison to previous, systemic therapies the actual therapy is more effective? Q2: In comparison to previous, systemic therapies the actual therapy is more convenient in application? Q3: In comparison to previous, systemic therapies the actual therapy has less side effects? Q4: In comparison to previous, systemic therapies the actual therapy is better tolerable? Q5: In comparison to previous, systemic therapies I prefer the actual therapy?

14 Overview of Adverse Events Patients, n (%) Safety Population n=108 1 AE 27 (25.0) 1 treatment-related AE 18 (16.7) 1 treatment-related AE with at least moderate intensity 14 (13.0) 1 AE leading to drug withdrawal 9 (8.3) 1 SAE 1 (0.9) 1 treatment-related SAE 1 (0.9) Most common AEs,* n (%) Diarrhea 9 (8.3) Nausea 2 (1.2) Upper respiratory tract infection 1 (0.9) Headache 2 (1.9) The overall incidence rate of AEs is lower than that in clinical studies. Only 1 patient was affected by severe AEs (obstipation, tremor, palpitations). *Reported by 5% of patients in phase 3 clinical trials of apremilast. Interim analysis includes total number of SAEs and related AEs. Nonserious AEs were asked to be reported upon termination. SAE=serious adverse event.

15 Conclusions The interim analysis presents the first data on apremilast for the treatment of patients with moderate to severe plaque psoriasis under clinical routine in Germany. Efficacy of apremilast in daily practice is comparable or superior to clinical trial results. Patient quality of life is rapidly and significantly improved (shown by DLQI reponse). Patient satisfaction is high under apremilast treatment compared with previous systemic treatments. Apremilast was generally well tolerated; rate of discontinuation due to AEs was low. The safety profile in this real-world setting was consistent with clinical trials of apremilast in psoriasis. 1,2 1. Papp K, et al. J Am Acad Dermatol. 2015;73: Paul C, et al. Br J Dermatol. 2015;173: