Efficacy and Safety of Apremilast in Patients With Moderate Plaque Psoriasis (UNVEIL Phase IV Study)

Transcription

1 4892 Efficacy and Safety of Apremilast in Patients With Moderate Plaque Psoriasis ( Phase IV Study) Bruce Strober, MD 1 ; Jerry Bagel, MD 2 ; Mark Lebwohl, MD 3 ; Linda Stein Gold, MD 4 ; J. Mark Jackson, MD 5 ; Rongdean Chen, PhD 6 ; Joana Goncalves, MD 6 ; Eugenia Levi, PharmD 6 ; Kristina Callis Duffin 7 1 University of Connecticut, Farmington, CT, and Probity Medical Research, Waterloo, ON, Canada; 2 Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ; 3 Icahn School of Medicine at Mount Sinai, New York, NY; 4 Henry Ford Health System, West Bloomfield, MI; 5 University of Louisville, Forefront Dermatology, Louisville, KY; 6 Celgene Corporation, Summit, NJ; 7 University of Utah, Salt Lake City, UT 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 Bruce Strober Disclosures BS: AbbVie, Amgen, Astra Zeneca, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Forward Pharma, Janssen, Leo, Maruho, Medac, Novartis, Pfizer, Stiefel/GlaxoSmithKline, Sun Pharma, and UCB honoraria as a consultant and advisory board member; AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Merck, Novartis, and Pfizer payments (to the University of Connecticut) as an investigator; CORRONA Psoriasis Registry fees as a scientific director; AbbVie and Janssen grant support (to the University of Connecticut for Fellowship Program). JB: AbbVie, Amgen, Boehringer Ingelheim, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, and Valeant speaker board member, consultant, and/or research support. ML: Mount Sinai, which receives funds from Boehringer Ingelheim, Celgene Corporation, Eli Lilly, Janssen/Johnson & Johnson, Kadmon, MedImmune/AstraZeneca, Novartis, Pfizer, and ViDac employment. LSG: Celgene Corporation, LEO Pharma, Novartis, Pfizer, and Stiefel/GlaxoSmithKline investigator and/or consultant JMJ: AbbVie, Amgen, Celgene Corporation, Dermira, Galderma, Genentech, Janssen, Lilly, Medimetriks, Merck, Novartis, Pfizer, Promius, and TopMD research, honoraria, consulting, and/or other support. RC, JG, & EL: Celgene Corporation employment. KCD: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene Corporation, Centocor/Janssen, Eli Lilly, Novartis, Pfizer, Regeneron, Stiefel, and XenoPort consultant, steering committee member, advisory board member, has received grants, and/or has received honoraria.

3 Introduction Patients with moderate plaque psoriasis are often inadequately treated, and there remains an unmet medical need for an effective and convenient treatment option in this population. 1 In the Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey of patient and physician perceptions of satisfaction with current psoriasis therapies, >80% of psoriasis patients with 4 to 10 palms body surface area (BSA) involvement reported receiving no treatment or topical treatment only. 2 In addition, 57% of psoriasis patients reported discontinuing therapy, most often for safety or tolerability reasons and lack or loss of efficacy. 2 Apremilast is an oral, small-molecule phosphodiesterase 4 inhibitor that works intracellularly to regulate inflammatory mediators, including pathways relevant to the pathogenesis of psoriasis. 3 Apremilast has been shown to be effective and demonstrated acceptable tolerability in patients with moderate to severe psoriasis in the ESTEEM phase 3 clinical trial program. 4,5 (NCT ) is the first prospective, randomized, controlled trial to evaluate the clinical efficacy and safety of a systemic treatment, oral apremilast 30 mg BID (APR), in patients with moderate plaque psoriasis with BSA involvement of 5% to 10% who are naive to systemic and biologic therapy. ESTEEM=Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis; =Evaluating Apremilast in a Phase IV Trial of Efficacy and Safety in Patients With Moderate Plaque Psoriasis. 1. Armstrong AW, et al. JAMA Dermatol. 2013;149: Lebwohl MG, et al. J Am Acad Dermatol. 2014;70: Schafer PH, et al. Cell Signal. 2014;26: Papp K, et al. J Am Acad Dermatol. 2015;73(1): Paul C, et al. Br J Dermatol. 2015;173(6):

4 : Study Design Placebo-Controlled Phase Open-label Treatment Phase Safety Observation 5 Weeks Week 0 Week 16 Week 52 Week 56 SCREEN* RANDOMIZE 1:2 Apremilast 30 mg BID Placebo Apremilast 30 mg BID ClinicalTrials.gov: NCT Primary end point: Mean percentage change in PGAxBSA at Week 16 *Screening up to 35 days before randomization. All doses were titrated over the first week of treatment. At Week 16, all placebo patients were switched to open-label apremilast 30 mg BID (with dose titration) through Week 52. PGAxBSA=product of the static Physician s Global Assessment and body surface area involvement.

5 Study Objectives and Key Inclusion Criteria Study Objective To evaluate the clinical efficacy and safety of APR vs. placebo (PBO) in patients with moderate plaque psoriasis during the 16-week placebo-controlled phase Key Inclusion Criteria Males or females 18 years of age Chronic plaque psoriasis for 6 months before screening Moderate plaque psoriasis at screening and baseline as defined by BSA of 5% to 10% spga of 3 (moderate) based on a 0 to 5 scale No prior exposure to systemic treatments or biologics for the treatment of psoriatic arthritis, psoriasis, or any other indication that could affect the assessment of psoriasis spga=static Physician s Global Assessment.

6 Baseline Patient Demographics and Disease Characteristics PBO n=73 APR n=148 Age, mean (SD), years 51.1 (13.7) 48.6 (15.4) Male, n (%) 41 (56.2) 74 (50.0) BMI, mean (SD), kg/m (6.5) 30.5 (7.4) Duration of plaque psoriasis, mean (SD), years 13.9 (12.6) 17.5 (13.9) PGAxBSA score, mean (SD) 21.6 (5.9) 21.8 (5.3) BSA, %, mean (SD) 7.1 (1.8) 7.2 (1.6) PASI score (0-72), mean (SD) 8.0 (3.2) 8.2 (4.0) DLQI total score, mean (SD) 11.1 (6.5) 11.0 (6.5) ScPGA score 1, n (%) 55 (75.3) 112 (75.7) Prior topical therapy, n (%) 59 (80.8) 122 (82.4) At baseline, >80% of patients had received topical therapy before enrollment. BMI=body mass index; DLQI=Dermatology Life Quality Index; PASI=Psoriasis Area and Severity Index; ScPGA=Scalp Physician s Global Assessment.

7 Mean Percentage Change in PGAxBSA at Week 16 Patients who received APR had a significantly greater improvement (reduction) in mean percentage change from baseline in PGAxBSA vs. the PBO group at Week 16. In addition, 35.1% of APR patients achieved a 75% reduction from baseline in PGAxBSA score (PGAxBSA-75) vs. 12.3% of PBO patients (P<0.0001). Mean Percentage Change in PGAxBSA (LOCF) PGAxBSA-75 Response (LOCF) Mean Percentage Change From Baseline in PGAxBSA PBO n= APR n= * PGAxBSA-75 Response, % PBO n=73 * 35.1 APR n=148 *P< vs. PBO. LOCF=last observation carried forward.

8 Patient With Psoriasis Treated With APR Baseline: BSA=9%; PGA=3 Week 16: BSA=1%; PGA=1

9 Proportions of Patients Achieving spga Score of 0 (Clear) or 1 (Almost Clear) at Week 16 Significantly more patients receiving APR achieved an spga score of 0 (clear) or 1 (almost clear) at Week 16 compared with PBO. Percentage of Patients Achieving spga Score of 0 or spga Response at Week 16 (LOCF) 9.6 PBO n=73 * 30.4 APR n=148 *P< vs. PBO.

10 Mean Percentage Change From Baseline in PGAxBSA and PASI Scores Mean percentage changes from baseline in PGAxBSA and PASI scores over the course of the 16-week PBO-controlled period are shown below; improvement from baseline was greater with PGAxBSA vs. PASI at each time point. Study Week Mean Percentage Change From Baseline PBO PASI APR PASI PBO PGAxBSA APR PGAxBSA

11 Scalp Psoriasis Response at Week 16 More than 75% (n=167) of enrolled patients presented with scalp psoriasis (ScPGA score 1). At Week 16, significantly more patients treated with APR vs. PBO achieved an ScPGA response (score of 0 [clear] or 1 [minimal]) with 2-point reduction from baseline (38% vs. 20%, P=0.0178). Patient With Scalp Psoriasis Treated With APR Baseline ScPGA=3 Week 16 ScPGA=2

12 Overview of Adverse Events Overview Patients, n (%) PBO-Controlled Period 0 to 16 Weeks Marked abnormalities with APR in clinical laboratory parameters were transient in nature and generally comparable with the PBO group. PBO n=73 APR n=147 1 AE 35 (47.9) 92 (62.6) 1 serious AE 0 (0.0) 3 (2.0) 1 severe AE 1 (1.4) 3 (2.0) AE leading to drug withdrawal 3 (4.1) 5 (3.4) Reported by 5 % of patients in any treatment group, n (%) Diarrhea 12 (16.4) 43 (29.3) Headache 8 (11.0) 30 (20.4) Nausea 7 (9.6) 26 (17.7) Upper respiratory tract infection 3 (4.1) 10 (6.8) Decreased appetite 4 (5.5) 6 (4.1) Vomiting 2 (2.7) 9 (6.1)

13 Conclusions APR was effective in systemic-naive, post-topical patients with more moderate plaque (BSA 5% to 10%) psoriasis and was generally well tolerated. The efficacy and safety of APR are consistent with those seen in patients with moderate to severe plaque psoriasis in randomized phase 3 trials. 1,2 1. Papp K, et al. J Am Acad Dermatol. 2015;73: Paul C, et al. Br J Dermatol. 2015;173: