PowerPoint Presentation
PRESENTED AT 2021 FALL CLINICAL DERMATOLOGY CONFERENCE, LAS VEGAS, NV, USA, OCTOBER 21–24, 2021
Long-term Safety and Efficacy of Roflumilast Cream 0.3% in Adult Patients With Chronic Plaque Psoriasis:
Results From a 52-Week, Phase 2b Open-Label Study
• 94% of AEs were rated mild or moderate
• 97% of AEs were unrelated or unlikely to be related to treatment as determined by the investigator
• Rates of gastrointestinal and psychiatric AEs were low
• ≥97% of patients had no evidence of irritation per physician assessment at each visit
CONCLUSIONS
• Patients with chronic plaque psoriasis need topical treatments that provide effective control of
psoriasis with low incidence of side effects that can be used for long-term treatment
• In this phase 2 long-term safety study, roflumilast cream, an investigational, once-daily,
nonsteroidal topical PDE-4 inhibitor, was well-tolerated with no new safety signals
– Rates of discontinuations due to AEs and lack of efficacy were low
• Durable efficacy was observed and the effect was maintained through 52 weeks of treatment
in this long-term safety study and up to 64 weeks including the phase 2b study
– Similar durability of effect was observed in patients with intertriginous area involvement
• Once-daily roflumilast cream is a promising novel therapy for treating plaque psoriasis
Linda Stein Gold,1 Melinda J. Gooderham,2 Kim A. Papp,3 Laura K. Ferris,4 Mark Lebwohl,5 David N. Adam,6 Javier Alonso-Llamazares,7 H. Chih-ho Hong,8 Steven E. Kempers,9 Leon H. Kircik,10 Wei Jing Loo,11 Walter K. Nahm,12 Daniel Stewart,13 Matthew Zirwas,14 Patrick Burnett,15 Robert C. Higham,15
Lynn Navale,15 David R. Berk15
1Henry Ford Medical Center, Detroit, MI, USA; 2SkiN Centre for Dermatology, Probity Medical Research and Queen’s University, Peterborough, ON, Canada; 3Probity Medical Research and K. Papp Clinical Research, Waterloo, ON, Canada; 4University of Pittsburgh, Department of Dermatology, Pittsburgh, PA, USA; 5Icahn School of Medicine at Mount Sinai, New York, NY, USA; 6CCA Medical Research, Probity Medical Research and Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada;
7Driven Research LLC, Coral Gables, FL, USA; 8Probity Medical Research and University of British Columbia, Department of Dermatology and Skin Science, Surrey, BC, Canada; 9Minnesota Clinical Study Center, Fridley, MN, USA; 10Icahn School of Medicine at Mount Sinai, New York, NY, Indiana Medical Center, Indianapolis, IN, Physicians Skin Care, PLLC, Louisville, KY, and Skin Sciences, PLLC, Louisville, KY, USA; 11DermEffects, London, ON, Canada; 12University of California, San Diego, School of Medicine,
San Diego, CA, USA; 13Michigan Center for Skin Care Research, Clinton Township, MI, USA; 14Dermatologists of the Central States, Probity Medical Research, and Ohio University, Bexley, OH, USA; 15Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA
REFERENCES
1. Dong C, et al. J Pharmacol Exp Ther 2016;358:413-422.
2. Lebwohl MG, et al. N Engl J Med 2020;383:229-239.
ACKNOWLEDGEMENTS
• This study was supported by Arcutis Biotherapeutics, Inc.
• Thank you to the investigators and their staff for their participation in the trial
• We are grateful to the study participants and their families for their time and commitment
• Writing support was provided by by Christina McManus, PhD, Alligent Biopharm Consulting LLC, and funded by Arcutis Biotherapeutics, Inc.
DISCLOSURES
LSG, MG, KAP, LKF, ML, DNA, JA-L, HCH, SEK, LHK, WJL, WKN, DS, and MZ are investigators and/or consultants for Arcutis Biotherapeutics,
Inc. and received grants/research funding and/or honoraria; PB, RCH, LN, and DRB are or were employees of Arcutis Biotherapeutics, Inc.
Additional disclosures provided on request.
INTRODUCTION
• Topical treatment options for chronic plaque psoriasis lack products that are safe with long-term usage, are well tolerated, and are used as single agents
over the entire body
• Roflumilast cream, a phosphodiesterase-4 (PDE-4) inhibitor that is more potent than other PDE-4 inhibitors,1 is under investigation as a once-daily,
nonsteroidal, topical treatment for psoriasis
• In a phase 2b randomized, double-blind, 12-week trial of 331 adults with chronic plaque psoriasis, roflumilast cream once daily was found to be superior
to vehicle cream and was well tolerated2
• This multicenter, open-label, 52-week study was also conducted to assess long-term safety of roflumilast 0.3% cream in patients with chronic plaque
psoriasis
RESULTS
Figure 2. Patient Disposition
AE: adverse event.
High completion rate with low rate of discontinuations due to AEs or lack of efficacy
Overall, N=332 Enrolled
Cohort 1 (n=230) +
Cohort 2 (n=102)
Completed Study n=244 (73.5%)
Discontinued, n=88 (26.5%)
Withdrawal: n=36 (10.8%)
Lost to follow-up: n=34 (10.2%)
Lack of efficacy: n=3 (0.9%)
AE: n=13 (3.9%)
Other: n=2 (0.6%)
Figure 1. Study Design
*Excludes scalp, palms, soles.
BSA: body surface area; IGA: Investigator Global Assessment; QD: once daily; PASI: Psoriasis Area Severity Index; SAE: serious adverse event; TEAE: treatment-emergent adverse event.
Roflumilast Cream 201 Phase 2b
(NCT03638258)2
Roflumilast Cream 202
Phase 2 Long-term Safety (NCT03764475)
ELIGIBILITY
• Diagnosis of at least
mild plaque psoriasis
• Age ≥18 years
• 2-20% BSA*
Roflumilast cream
0.3% QD
Roflumilast cream
0.15% QD
Vehicle
QD
ENDPOINTS
• Primary: Safety
– Occurrence of TEAEs
– Occurrence of SAEs
• Secondary: Efficacy
– IGA clear or almost clear skin
– Intertriginous-IGA clear or
almost clear skin
– PASI
– BSA
12 weeks
Ra
nd
om
iz
at
io
n
1:1:1
N=331
ELIGIBILITY
• Diagnosis of at least mild plaque
psoriasis for at least 6 months
• Age ≥18 years
• 2-25% BSA*
COHORT 1 (Rollovers)
Roflumilast cream 0.3% QD
52 weeks
COHORT 2 (Naïve)
Roflumilast cream 0.3% QD
Completed
Study 201 through
12 weeks
Table 1. Baseline Disease Characteristics
Cohort 1 Total
(n=230)
Cohort 2 Total
(n=102)
Overall Total
(N=332)
BSA, mean % 6.2 6.6 6.3
PASI, mean 7.2 6.8 7.1
IGA score, n (%)
1 (almost clear) 8 (3.5) 0 (0.0) 8 (2.4)
2 (mild) 51 (22.2) 17 (16.7) 68 (20.5)
3 (moderate) 156 (67.8) 78 (76.5) 234 (70.5)
4 (severe) 15 (6.5) 7 (6.9) 22 (6.6)
Intertriginous Involvement (I-IGA ≥2)
I-IGA, n (%)
2 (mild) 19 (8.3) 12 (11.8) 31 (9.3)
3 (moderate) 17 (7.4) 12 (11.8) 29 (8.7)
4 (severe) 2 (0.9) 0 (0.0) 2 (0.6)
Baseline is defined as the last observation prior to the first dose of roflumilast cream in either the ARQ-151-201 or ARQ-151-202 study.
BSA: body surface area; IGA: Investigator Global Assessment; I-IGA: Intertriginous Investigator Global Assessment; PASI: Psoriasis Area and Severity Index.
Patients Achieving IGA Success (IGA = 0/1 plus a 2-grade improvement)
Figure 4. The Proportion of Patients Achieving IGA status of ‘Clear’ or ‘Almost Clear’ With Roflumilast Was Consistent Over Time
IGA: Investigator Global Assessment.
• Of patients receiving roflumilast cream 0.3% in the parent trial who achieved IGA of clear/almost clear at 12 weeks and continued in the open-label trial, 66.7% achieved IGA of
clear/almost clear at 64 weeks or their last visit
25.7
34.7 31.9
28.7
34.8
0
10
20
30
40
50
60
70
80
90
100
Week 16
(n=218)
Week 24
(n=202)
Week 36
(n=182)
Week 48
(n=171)
Week 64
(n=158)
Pa
ti
en
ts
, %
17.2
40
34.5 36.7
39.5
0
10
20
30
40
50
60
70
80
90
100
Week 4
(n=99)
Week 12
(n=95)
Week 24
(n=87)
Week 36
(n=79)
Week 52
(n=81)
Pa
ti
en
ts
, %
Cohort 1
(Rollovers)
Cohort 2
(Naïve)
Time on treatment
V Patients Achieving IGA Success (IGA = 0/1 plus a 2-grade improvement)
Figure 3. Roflumilast Provided Durable Improvement in IGA
No imputation of missing values. Baseline is defined as the last observation prior to the first dose of ARQ-151 cream in either the ARQ-151-201 or ARQ-151-202 study.
IGA: Investigator Global Assessment.
0
10
20
30
40
50
60
70
80
90
100
2 4 6 8 12 16 24 36 48 64
Pa
ti
en
ts
, %
Roflumilast 0.3% (201) Roflumilast 0.15% (201) Vehicle (201) Roflumilast 0.3% (202)
Study 2012 Study 202 – All patients received roflumilast 0.3%
N 331331 218 182202 171 158331 331 331
Time on treatment
• Among all rollover groups, IGA success was between 33% and 37%, and exceeded that observed among these patients at Week 12 of the parent study
Patients Achieving I-IGA Success (I-IGA = 0/1 plus a 2-grade improvement)
Cohort 2 (Naïve)†
Figure 5. Roflumilast Provided Consistent Improvement of I-IGA‡
†Cohort 1 not shown because I-IGA added as study amendment and numbers of patients evaluated are very small at each timepoint; ‡Collected post-baseline for patients with a severity of at least mild.
I-IGA: Intertriginous-area Investigator Global Assessment.
42.9
60.0 60.0
56.3
66.7
0
10
20
30
40
50
60
70
80
90
100
Week 4
(n=21)
Week 12
(n=20)
Week 24
(n=20)
Week 36
(n=16)
Week 52
(n=15)
Pa
ti
en
ts
, %
Table 2. Summary of AEs (Safety Population)
TEAE, n (%)
Cohort 1
Total
(n=230)
Cohort 2
Total
(n=102)
Overall
Total
(N=332)
Patients with any TEAE 104 (45.2) 60 (58.8) 164 (49.4)
Patients with any treatment-related TEAE 7 (3.0) 5 (4.9) 12 (3.6)
Patients with any SAE 10 (4.3) 2 (2.0) 12 (3.6)
- Any treatment-related SAE 0 (0) 0 (0) 0 (0)
Patients who discontinued study drug due to AE 11 (4.8) 2 (2.0) 13 (3.9)
TEAE defined as event with an onset on or after the date of the first study drug application in ARQ-151-202 study.
AE: adverse event; SAE: serious adverse event; TEAE: treatment-emergent adverse event.
Table 3. Most Common AEs (>2% Overall)
TEAE, n (%)
Cohort 1
Total
(n=230)
Cohort 2
Total
(n=102)
Overall
Total
(N=332)
Upper respiratory tract infection/viral URTI 14 (6.1) 8 (7.8) 22 (6.6)
Urinary tract infection 9 (3.9) 4 (3.9) 13 (3.9)
Nasopharyngitis 8 (3.5) 5 (4.9) 13 (3.9)
Sinusitis/chronic sinusitis 3 (1.3) 6 (5.9) 9 (2.7)
Hypertension/essential hypertension 8 (3.5) 1 (1.0) 9 (2.7)
Arthralgia 7 (3.0) 1 (1.0) 8 (2.4)
Back pain 5 (2.2) 2 (2.0) 7 (2.1)
Cough 4 (1.7) 3 (2.9) 7 (2.1)
AE: adverse event; TEAE: treatment-emergent adverse event; URTI: upper respiratory tract infection.
Long-term Safety and Efficacy of Roflumilast Cream 0.3% in Adult Patients With Chronic Plaque Psoriasis: �Results From a 52-Week, Phase 2b Open-Label Study
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