PowerPoint Presentation
PRESENTED AT FALL CLINICAL DERMATOLOGY CONFERENCE 2022 MEETING, OCTOBER 20–23, 2022, LAS VEGAS, NV, USA
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 Christina McManus, PhD, and Lauren Ramsey, PharmD, Alligent Biopharm
Consulting LLC, and funded by Arcutis Biotherapeutics, Inc.
DISCLOSURES
LKF, AA, JD, ZDD, MG, ML, KAP, JS, and LSG are investigators and/or consultants for Arcutis Biotherapeutics,
Inc. and received grants/research funding and/or honoraria; DK, RCH, PB, and DRB are employees of Arcutis
Biotherapeutics, Inc. Additional disclosures provided on request.
INTRODUCTION
• Patients with psoriasis involving special areas, such as the face,
intertriginous, and genital areas, may have a disproportionately greater
negative impact on their quality of life than patients without psoriasis
involvement in those areas1
• Chronic use of current topical treatment options in these areas is limited
due to risk of local skin side effects or limitations on duration of use2
• Roflumilast is a selective and highly potent phosphodiesterase 4 (PDE4)
inhibitor with greater affinity for PDE4 than apremilast or crisaborole
and approximately 25- to >300-fold more potent based on in vitro
assays3
– Topical roflumilast is being investigated as a once-daily, nonsteroidal
treatment for long-term management of various dermatologic
conditions, including atopic dermatitis, seborrheic dermatitis, and
chronic plaque psoriasis (approved by the US Food and Drug
Administration July 29, 2022)
• Efficacy, safety, and tolerability of roflumilast cream 0.3% in psoriasis
have been demonstrated in a phase 2b study in patients with psoriasis;
the individual phase 3 DERMIS-1 and DERMIS-2 results were previously
reported4,5
• Here, we report the pooled results from 2 phase 3, randomized, double-
blind, vehicle-controlled, multicenter trials of once-daily roflumilast
cream 0.3% in patients with psoriasis (DERMIS-1 and DERMIS-2),
presenting subgroup analyses of patients with involvement of special
areas (SAs: defined as the face, and/or intertriginous, and/or genital
areas)
METHODS
• DERMIS-1 and DERMIS-2 were 2 identical, phase 3, randomized, double-
blind, vehicle-controlled, 8-week studies of once-daily roflumilast cream
0.3% in patients (≥2 years of age) with psoriasis (body surface area [BSA]
affected: 2%–20%; Figure 1)
• The primary efficacy endpoint was Investigator Global Assessment (IGA)
Success at Week 8, which was defined as achievement of Clear or
Almost Clear IGA status plus ≥2-grade improvement from baseline
CONCLUSIONS
• Roflumilast cream 0.3% provided improvement across multiple
efficacy endpoints versus vehicle cream while demonstrating
favorable safety and tolerability in patients with chronic plaque
psoriasis involving intertriginous, and/or face, and/or genital areas
in 2 phase 3 trials
• The local tolerability profile as assessed by both patients and
investigators was favorable
• The subgroup analysis of the pooled results of the phase 3
DERMIS-1 and DERMIS-2 trials showed that once-daily roflumilast
cream 0.3% demonstrated efficacy and tolerability in patients with
psoriasis involvement in difficult-to-treat areas
RESULTS
• Baseline disease characteristics and demographics
were similar across treatment groups (Table 1)
• Significantly more roflumilast-treated patients
achieved the primary endpoint, IGA Success at Week 8
(Figure 2)
– Across the subgroups at Week 8, a greater
percentage of patients in the roflumilast group
achieved IGA Success compared with that of the
vehicle group
– More patients in the roflumilast group also had an
IGA status of Clear or Almost Clear across
subgroups at Week 8 (Figure 3)
• More roflumilast-treated patients who had a baseline
score ≥4 on the Worst Itch Numeric Rating Scale
(WI-NRS) had a 4-point improvement at Week 8 across
subgroups (Figure 4)
• The least square mean percent change from baseline
in Psoriasis Symptoms Diary (PSD) scores was greater
after roflumilast treatment than with vehicle
treatment at Week 8 across subgroups (Figure 5)
Safety
• In patients with involvement in SA, local tolerability was highly favorable as
reported by patient and investigator assessment of irritation, burning, and
stinging (Figure 6)
– ≥97.6% of patients had no evidence of irritation at Week 8 on
investigator-rated assessments
– ≥97.2% reported no warmth/tingling sensation or mild sensation at
Week 8 on patient-rated assessments
• Overall incidence of treatment-emergent adverse events (TEAEs), serious
AEs, and TEAEs leading to discontinuation was low with similar rates
between roflumilast and vehicle across both studies
• No skin atrophy was seen in the SAs treated with topical roflumilast or
vehicle (Table 2)
Laura K. Ferris,1 April Armstrong,2 James Del Rosso,3 Zoe D. Draelos,4 Melinda Gooderham,5 Mark Lebwohl,6 Kim A. Papp,7 Jennifer Soung,8 Linda Stein Gold,9 David Krupa,10 Robert C. Higham,10 Patrick Burnett,10 David R. Berk10
1University of Pittsburgh, Department of Dermatology, Pittsburgh, PA, USA; 2Keck School of Medicine, Department of Dermatology, University of Southern California Los Angeles, CA, USA; 3JDR Dermatology Research Center, LLC, Las Vegas, NV, USA; 4Dermatology Consulting Services, High Point, NC, USA; 5SkiN Centre for Dermatology,
Probity Medical Research and Queen’s University, Peterborough, ON, Canada; 6Icahn School of Medicine at Mount Sinai, New York, NY, USA; 7Probity Medical Research and K Papp Clinical Research, Waterloo, ON, Canada; 8Southern California Dermatology, Santa Ana, CA, USA; 9Henry Ford Medical Center, Detroit, MI, USA;
10Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA
Efficacy and Tolerability of Roflumilast Cream 0.3% in Patients With Chronic Plaque Psoriasis Involvement on
the Face, Intertriginous, or Genital Areas: Pooled Results From Phase 3 Trials (DERMIS-1 and DERMIS-2)
Figure 1. Study Design
IGA Success = Clear or Almost Clear IGA status plus ≥2-grade improvement from baseline.
BSA: body surface area; IGA: Investigator Global Assessment; I-IGA: intertriginous IGA; PSD: Psoriasis Symptoms Diary; QD: once daily; SA: special areas
(SA: defined as the face, and/or intertriginous, and/or genital areas); WI-NRS: Worst Itch Numeric Rating Scale.
Endpoints
Primary
• IGA Success
at Week 8
Secondary
• I-IGA Success
• WI-NRS
• PSD
Safety and
tolerability
Eligibility
• At least mild
plaque
psoriasis
• Age 2+ years
• 2%–20% BSA
Roflumilast
cream
0.3% QD
n=576
Vehicle
cream
QD
n=305
8 weeks dosing
Visits: Weeks 2, 4, 8
2:1
Ra
nd
om
iz
e
Po
st
-h
oc
a
na
ly
si
s
SA
in
vo
lv
em
en
t
Roflumilast
cream
0.3% QD
n=218
Vehicle
cream
QD
n=111
DERMIS-1
N=439
NCT04211363
DERMIS-2
N=442
NCT04211389
Two identical, parallel,
phase 3
multicenter trials
Table 1. Baseline Demographics and Disease
Characteristics
n (%)
Roflumilast
Cream 0.3%
(n=576)
Vehicle
(n=305)
Age in years, mean (SD) 47.2 (14.6) 47.9 (15.0)
Sex, n (%)
Male 365 (63.4) 196 (64.3)
Female 211 (36.6) 109 (35.7)
Race, n (%)
American Indian or Alaska Native 4 (0.7) 2 (0.7)
Asian 41 (7.1) 20 (6.6)
Black or African American 21 (3.6) 17 (5.6)
Native Hawaiian or Other Pacific
Islander
5 (0.9) 1 (0.3)
White 474 (82.3) 250 (82.0)
Not reported 9 (1.6) 5 (1.6)
Other 19 (3.3) 9 (3.0)
More than 1 race 3 (0.5) 1 (0.3)
IGA score, n (%)
2 (mild) 101 (17.5) 44 (14.4)
3 (moderate) 426 (74.0) 240 (78.7)
4 (severe) 49 (8.5) 21 (6.9)
Psoriasis-affected BSA, mean % (SD) 6.7 (4.6) 7.6 (4.9)
I-IGA score, n (%)
1 (almost clear) 7 (1.2) 2 (0.7)
2 (mild) 58 (10.1) 29 (9.5)
3 (moderate) 54 (9.4) 33 (10.8)
4 (severe) 4 (0.7) 1 (0.3)
PASI, mean score (SD) 6.4 (3.2) 6.9 (3.6)
WI-NRS, mean score (SD) 5.7 (2.7) 5.9 (2.8)
WI-NRS score ≥4, n (%) 447 (77.6) 231 (75.7)
BSA: body surface area; IGA: Investigator Global Assessment; I-IGA: intertriginous IGA; PASI: Psoriasis Area Severity
Index; WI-NRS: Worst Itch Numeric Rating Scale; SD: standard deviation.
Table 2. Overall AEs6
n (%)
Roflumilast
Cream 0.3%
(n=576)
Vehicle
(n=305)
Patients with any TEAE 147 (25.5) 64 (21.0)
Patients with any treatment-related TEAE 23 (4.0) 11 (3.6)
Patients with any SAE 2 (0.3) 2 (0.7)
Patients who discontinued study due to AE 6 (1.0) 4 (1.3)
Most common TEAE (≥1% in the roflumilast group),
preferred term
Diarrhea 18 (3.1) 0
Headache 14 (2.4) 3 (1.0)
Insomnia 8 (1.4) 2 (0.7)
Nausea 7 (1.2) 1 (0.3)
Nasopharyngitis 6 (1.0) 4 (1.3)
Urinary tract infection 6 (1.0) 2 (0.7)
Application-site pain 6 (1.0) 1 (0.3)
Upper respiratory tract infection 6 (1.0) 1 (0.3)
AE: adverse event; SAE: serious adverse event; TEAE: treatment-emergent adverse event.
Figure 6. Investigator- and Patient-Rated Local Tolerability at Week 8
Patient-rated tolerability: 0 = None (no sensation), 1 = Mild (slight warm, tingling sensation), 2 = Moderate (definite warm, tingling sensation), 3 = Severe
(hot, tingling/stinging sensation).
98.6 97.6 98.4 95.0 100.098.4 99.1 100.0 96.9 98.1
0
10
20
30
40
50
60
70
80
90
100
Overall pooled
DERMIS
Intertriginous, facial,
genital involvement
Facial involvement Genital involvement Intertriginous
involvement
Roflumilast cream 0.3% Vehicle cream
99.5 98.9 98.3 97.3 98.998.8 98.2 98.6 97.2 98.2
0
10
20
30
40
50
60
70
80
90
100
Overall pooled
DERMIS
Intertriginous, facial,
genital involvement
Facial involvement Genital involvement Intertriginous
involvement
Roflumilast cream 0.3% Vehicle cream
Investigator-Rated Local Tolerability
% Patients With No Evidence of Irritation
Patient-Rated Local Tolerability
% Patients With No or Mild Sensation
Pa
ti
en
ts
, %
Pa
ti
en
ts
, %
REFERENCES
1. Merola JF, et al. Dermatol Ther 2018;31:e12589.
2. Elmets CA, et al. J Am Acad Dermatol 2021;84:432–470.
3. Dong C, et al. J Pharmacol Exp Ther 2016;358:413–422.
4. Lebwohl MG, et al. N Engl J Med 2020;383:229–239.
5. Lebwohl MG, et al. 30th Congress of the European Academy of Dermatology and Venereology (EADV)
Virtual, September 29–October 2, 2021.
6. Lebwohl MG, et al. American Academy of Dermatology (AAD), Boston, MA, March 25–29, 2022.
Figure 4. Percentage of Patients Achieving WI-NRS Success at Week 8
*P<0.05; **P<0.01; ***P<0.001; ****P<0.0001.
WI-NRS Success = ≥4-point improvement in patients with baseline WI-NRS score ≥4.
CI: confidence interval; WI-NRS: Worst Itch Numeric Rating Scale.
Figure 5. LS Mean Percent Change in PSD at Week 8
*P<0.05; **P<0.01; ***P<0.001; ****P<0.0001.
CI: confidence interval; LS: least square; PSD: Psoriasis Symptoms Diary.
Overall Any SA Facial Genital Intertriginous
0
10
20
30
40
50
60
70
80
90
100
%
P
at
ie
nt
s
(9
5%
C
I)
**** *
*****
****
Roflumilast Cream 0.3% Vehicle
n= 397 198 174 488085 106 55 69 30
Patients with psoriasis involving
Overall Any SA Facial Genital Intertriginous
–100
–90
–80
–70
–60
–50
–40
–30
–20
–10
0
LS
M
ea
n
Pe
rc
en
t
Ch
an
ge
(9
5%
C
I)
**** ****
****
******
Roflumilast Cream 0.3% Vehicle
n= 506 253 211 5597108 127 75 82 35
Patients with psoriasis involving
Figure 3. Percent of Patients With Involvement in
SAs Achieving IGA Status of Clear or Almost Clear
(A) and I-IGA Clear or Almost Clear (B) at Week 8
*P<0.05; **P<0.01; ***P<0.001; ****P<0.0001.
I-IGA Clear or Almost Clear IGA status evaluated in intertriginous areas only.
CI: confidence interval; IGA: Investigator Global Assessment; I-IGA: intertriginous IGA; SA: special area.
Figure 2. Percent of Patients With Involvement in
SAs Achieving IGA Success (A) and I-IGA Success (B)
at Week 8
*P<0.05; **P<0.01; ***P<0.001; ****P<0.0001.
IGA Success = Clear or Almost Clear IGA status plus ≥2-grade improvement from baseline; I-IGA Success = Clear or
Almost Clear IGA status plus ≥2-grade improvement from baseline evaluated in intertriginous areas only.
CI: confidence interval; IGA: Investigator Global Assessment; I-IGA: Intertriginous-IGA; SA: special areas.
Overall Any SA Facial Genital Intertriginous
0
10
20
30
40
50
60
70
80
90
100
Pa
ti
en
ts
, %
(9
5%
C
I)
****
**** **********
Roflumilast Cream 0.3%
Vehicle
n= 519 263 218 5699111 133 76 84 37
Patients with psoriasis involving
A IGA Clear or Almost Clear
B I-IGA Clear or Almost Clear
Intertriginous area only
0
10
20
30
40
50
60
70
80
90
100
Pa
ti
en
ts
, %
(9
5%
C
I)
Roflumilast Cream 0.3%
Vehicle
99 56n=
Overall Any SA Facial Genital Intertriginous
0
10
20
30
40
50
60
70
80
90
100
%
P
at
ie
nt
s
(9
5%
C
I)
****
**** ******
****
n= 519 263 218 5699111 133 76 84 37
Roflumilast Cream 0.3%
Vehicle
Patients with psoriasis involving
Intertriginous area only
0
10
20
30
40
50
60
70
80
90
100
Pa
ti
en
ts
, %
(9
5%
C
I) **
99 56n=
Roflumilast Cream 0.3%
Vehicle
A. IGA Success
B. I-IGA Success
Efficacy and Tolerability of Roflumilast Cream 0.3% in Patients With Chronic Plaque Psoriasis Involvement on the Face, Intertriginous, or Genital Areas: Pooled Results From Phase 3 Trials (DERMIS-1 and DERMIS-2)
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