PowerPoint Presentation
PRESENTED AT 2021 FALL CLINICAL DERMATOLOGY CONFERENCE, LAS VEGAS, NV, USA, OCTOBER 21–24, 2021
aProtocol amendment 2: S-IGA entry criterion changed from ≥2 (mild) to ≥3 (moderate). S-IGA/B-IGA Success: IGA status of
clear or almost clear plus ≥2-grade improvement from baseline. B-IGA: Body-Investigator Global Assessment; BSA: body
surface area; DLQI: Dermatology Life Quality Index; IGA: Investigator Global Assessment; NRS: Numeric Rating Scale; PASI:
Psoriasis Area Severity Index; PSD: Psoriasis Symptom Diary; PSSI: Psoriasis Scalp Severity Index; QD: once daily; S-IGA:
Scalp-Investigator Global Assessment; SI-NRS: Scalp Itch-Numeric Rating Scale; WI-NRS: Worst Itch-Numeric Rating Scale.
Figure 1. Study Design
Once-Daily Roflumilast Foam 0.3% Improves Severity and Burden of Itch in Patients With
Scalp and Body Psoriasis in a Randomized, Double-blind, Vehicle-Controlled Phase 2b Study
Angela Y. Moore,1 Javier Alonso-Llamazares,2 Neal Bhatia,3 Michael Bukhalo,4 Alim R. Devani,5 Zoe D. Draelos,6 Melinda J. Gooderham,7 Steven E. Kempers,8 Leon H. Kircik,9 Kim A. Papp,10 David M. Pariser,11 Marina Sankeva,12 Rodney Sinclair,13
Matthew Zirwas,14 Amy Feng,15 Patrick Burnett,15 Robert Higham,15 David Berk15
1Arlington Center for Dermatology, Arlington Research Center, Arlington, TX and Baylor University Medical Center, Dallas, TX, USA; 2Driven Research LLC, Coral Gables, FL, USA; 3Therapeutics Clinical Research, San Diego, CA, USA; 4Arlington Dermatology, Rolling Meadows, IL, USA; 5Dermatology Research Institute and Probity Medical Research, Calgary, AB, Canada; 6Dermatology Consulting Services,
High Point, NC, USA; 7SkiN Centre for Dermatology, Probity Medical Research and Queen’s University, Peterborough, ON, Canada; 8Minnesota Clinical Study Center, Fridley, MN, USA; 9Icahn School of Medicine at Mount Sinai, NY, Indiana Medical Center, Indianapolis, IN, Physicians Skin Care, PLLC, Louisville, KY, and Skin Sciences, PLLC, Louisville, KY, USA; 10Probity Medical Research and K Papp
Clinical Research, Waterloo, ON, Canada; 11Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA, USA; 12Private Practice, Gabrovo, Bulgaria; 13Sinclair Dermatology, East Melbourne, Victoria, Australia; 14Dermatologists of the Central States, Probity Medical Research, and Ohio University, Bexley, OH, USA; 15Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA
INTRODUCTION
• In patients with psoriasis, about 80% have scalp psoriasis1
– Scalp psoriasis is often associated with itch, the most burdensome symptom of
psoriasis2
– Itching, flaking, and plaque visibility on the scalp can cause social embarrassment
and adversely impact quality of life3
– Treatment of scalp psoriasis is difficult because the hair may limit efficacy of
creams and ointments and reduce treatment adherence4
• Roflumilast is a selective and highly potent phosphodiesterase-4 inhibitor being
investigated as a once-daily, nonsteroidal, topical treatment for various dermatologic
conditions
– Roflumilast foam is uniquely formulated as an emollient, water-based,
moisturizing foam that can be used on the scalp or body
– Roflumilast cream met the primary and secondary endpoints and was well-
tolerated in a phase 2b, randomized, double-blind, vehicle-controlled trial in adults
with psoriasis5
• We investigated roflumilast foam for scalp and body psoriasis in a phase 2b,
randomized, double-blind, vehicle-controlled 8-week study (ClinicalTrials.gov
Identifier: NCT04128007)
METHODS
• This was a parallel-group, double-blind, vehicle-controlled clinical trial (Figure 1)
• Eligible patients were adults and adolescents ≥12 years old with diagnoses of scalp
and body psoriasis for at least 6 months
• Patients were randomized 2:1 to roflumilast 0.3% or matching vehicle foam
• The primary efficacy endpoint was scalp-Investigator Global Assessment (S-IGA)
Success, defined as achievement of an S-IGA score of clear or almost clear plus a
2-grade improvement from baseline at Week 8
• Efficacy endpoints were analyzed using a Cochran-Mantel-Haenszel test stratified by
country, baseline S-IGA, and baseline body-IGA (B-IGA) category using multiple
imputation for missing data
– Statistical tests were conducted at the 5% significance level using 2-tailed tests
ENDPOINTS
Primary
• S-IGA Success
Secondary
• B-IGA Success
• SI-NRS
• WI-NRS
• PSD
• DLQI
Safety and tolerability
8 weeks dosing
visits: Weeks 2, 4,
8, plus 1 week
post-treatment
ELIGIBILITY
• Aged ≥12 years
• Diagnosis of scalp and
body plaque psoriasis
• At least mild severitya
on both S-IGA and B-IGA
• ≤25% BSA
• PSSI ≥6
• ≥10% of scalp involved
• PASI ≥2
Roflumilast
foam 0.3% QD
(n=200)
Vehicle QD
(n=104)
Ra
nd
om
iz
e
2:1
N=304
• 96% power at α=0.05 to detect 22.4% difference between groups for S-IGA
Success, based on 201 results showing 32.2% vs 9.8% IGA Success at Week 85
RESULTS
• A total of 304 patients were randomized to roflumilast foam 0.3% (n=200) or vehicle
foam (n=104; intent-to-treat [ITT] population; Table 1)
– Of these, 198 patients in the roflumilast group (99%) and 104 in the vehicle group
(100%) received ≥1 confirmed dose of their study intervention (safety population)
• Most patients (83.7% to 88.5%) completed the study (Table 1)
• Baseline disease characteristics were balanced across treatment groups (Table 2)
CONCLUSIONS
• Patients with scalp psoriasis need topical treatments that provide effective control of psoriasis with low incidence
of side effects
• In this phase 2b study, once-daily roflumilast foam significantly improved both scalp and body psoriasis, apparent
as early as 2 weeks after treatment initiation
– Scalp and body itch abated by week 2 with further reduction throughout the study
• Roflumilast foam was well-tolerated with low rates of treatment-emergent AEs, application-site AEs, and
discontinuations due to AE
– Rates of these events were similar to vehicle
• Favorable safety profile and encouraging efficacy results warrant further investigation of once-daily roflumilast
foam as a potential novel therapy for the treatment of scalp and body psoriasis
DISCLOSURES
AYM, JA-L, NB, MB, ARD, ZDD, MJG, SEK, LHK, KAP, DMP, MS, RS, and MZ are investigators and/or consultants for Arcutis
Biotherapeutics, Inc. and received grants/research funding and/ or honoraria; AF, PB, RCH, and DRB are employees of Arcutis
Biotherapeutics, Inc. Additional disclosures provided on request.
Safety
• Rates of treatment-emergent AEs and discontinuation due to AEs were low (Table 3)
• Treatment-related AEs were uncommon
• Only 1 patient had a serious AE (unrelated)
• Very few AEs led to study discontinuation
– Discontinuation rates were similar between groups
• ≥99% of roflumilast- and ≥98% of vehicle-treated patients had no evidence of irritation on the investigator rating of
local tolerability
Table 3. Adverse Events
TEAEs, n (%)
Roflumilast Foam 0.3%
(n=198)
Vehicle Foam
(n=104)
Patients with any TEAE 46 (23.2) 20 (19.2)
Patients with any treatment-related TEAE 8 (4.0) 9 (8.7)
Patients with any serious AEa 1 (0.5) 0
Patients who discontinued study due to AEb 5 (2.5) 2 (1.9)
Most common TEAE (>1.5% in any group), preferred term
Application-site pain 2 (1.0) 4 (3.8)
COVID-19 3 (1.5) 2 (1.9)
Psoriasis 1 (0.5) 2 (1.9)
Sinusitis 1 (0.5) 2 (1.9)
Hypertension 3 (1.5) 1 (1.0)
Diarrhea 3 (1.5) 0
aSerious AE: testicular torsion, unrelated. bAE leading to discontinuation: roflumilast: application-site pruritus, abdominal discomfort, diarrhea, headache, application-site pain,
application-site discoloration, application-site irritation, lethargy; vehicle arm: psoriasis, application-site dermatitis. AE: adverse event; TEAE: treatment-emergent adverse event.
Figure 2. Percentages of Patients Achieving S-IGA Success (A) and B-IGA Success (B)
aIntent-to-treat population. B-IGA: Body-Investigator Global Assessment; CI: confidence interval; S-IGA: Scalp-Investigator Global Assessment.
9.5%
21.3%
40.3%
1.0%
5.6% 6.8%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Week 2 Week 4 Week 8
%
o
f P
at
ie
nt
s
(9
5%
C
I)
Roflumilast foam 0.3% (n=200) Vehicle foam (n=104)
P=0.0079
P<0.0001
P=0.0011
26.0% of patients on roflumilast achieved B-IGA status of
clear versus 3.4% on vehicle
100
90
80
70
60
50
40
30
20
10
0
17.4%
41.3%
59.1%
3.1% 5.6%
11.4%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Week 2 Week 4 Week 8
%
o
f P
at
ie
nt
s
(9
5%
C
I)
Roflumilast foam 0.3% (n=200) Vehicle foam (n=104)
P=0.0007
P<0.0001
P<0.0001
34.3% of patients on roflumilast achieved S-IGA status of clear
versus 3.4% on vehicle
100
90
80
70
60
50
40
30
20
10
0
S-IGA Success = Clear or almost clear plus ≥2-grade
improvement from baselinea
B-IGA Success = Clear or almost clear plus ≥2-grade
improvement from baselinea
(A) (B)
Figure 3. Percentages of Patients Achieving SI-NRS 4-Point Response (A) and WI-NRS 4-Point Response (B)
To control for multiple comparisons among the secondary endpoints, a multiplicity procedure was used. Upon successful testing of the primary endpoint, the α was partitioned to test secondary endpoints.
aEvaluated in patients with SI-NRS Score ≥4 at baseline; bevaluated in patients with WI-NRS score ≥4 at baseline. CI: confidence interval; SI-NRS: Scalp Itch-Numeric Rating Scale; WI-NRS: Worst Itch-Numeric Rating Scale.
Figure 4. PSD Item 1 (Severity of Itch; A) and Item 2 (Burden of Itch; B)
Table 1. Patient Disposition
n (%)
Roflumilast Foam 0.3%
(n=200)
Vehicle Foam
(n=104)
Completed 177 (88.5) 87 (83.7)
Prematurely discontinued 23 (11.5) 17 (16.3)
Reason for discontinuation
Withdrawal by subject 9 (4.5) 6 (5.8)
Noncompliance 1 (0.5) 0
Protocol violation 0 0
Lost to follow-up 8 (4.0) 7 (6.7)
Adverse event 5 (2.5) 2 (1.9)
Other 0 2 (1.9)
Table 2. Baseline Disease Characteristics (ITT Population)
n (%)
Roflumilast Foam 0.3%
(n=200)a
Vehicle Foam
(n=104)
BSA, mean % 8.0 7.6
Baseline S-IGA
2 – Mild 18 (9.0) 14 (13.5)
3 – Moderate 151 (75.5) 80 (76.9)
4 – Severe 29 (14.5) 10 (9.6)
Baseline B-IGA
2 – Mild 69 (34.5) 39 (37.5)
3 – Moderate 119 (59.5) 60 (57.7)
4 – Severe 10 (5.0) 5 (4.8)
PSSI, mean (SD) 22.4 (12.5) 20.9 (11.7)
PASI, mean (SD) 7.2 (4.3) 6.8 (4.4)
SI-NRS, mean (SD) 6.4 (2.4) 6.6 (2.3)
SI-NRS, ≥4, n (%) 173 (86.5) 96 (92.3)
WI-NRS, mean (SD) 6.4 (2.48) 6.7 (2.32)
WI-NRS ≥4, n (%) 165 (82.5) 94 (90.4)
PSD total score mean (SD) 78.5 (39.92) 84.3 (38.76)
PSD Item 1: severity of itch,
mean (SD)
6.3 (2.54) 6.7 (2.07)
PSD Item 2: burden of itch,
mean (SD)
6.1 (2.73) 6.5 (2.50)
DLQI, mean (SD) 6.6 (5.18) 6.8 (4.66)
aTwo patients were missing baseline values due to capture outside of the date-time visit window and were not evaluable. B-IGA: Body-Investigator
Global Assessment; BSA: body surface area; DLQI: Dermatology Life Quality Index; ITT: intent-to-treat; PASI: Psoriasis Area Severity Index; PSD:
Psoriasis Symptom Diary; PSSI: Psoriasis Scalp Severity Index; SD: standard deviation; S-IGA: Scalp-Investigator Global Assessment; SI-NRS: Scalp
Itch-Numeric Rating Scale; WI-NRS: Worst Itch-Numeric Rating Scale.
• Rates of discontinuation due to adverse event (AE) were low
Efficacy
• Roflumilast foam significantly improved scalp and body psoriasis at all timepoints (Figure 2)
• Roflumilast significantly improved scalp and body itch by Week 2 and consistently improved itch
through Week 8 (Figure 3)
• Roflumilast foam significantly improved patient-reported severity and burden of itch as indicated by
improvements on the Psoriasis Symptom Diary (PSD) Items 1 (Severity of Itch) and 2 (Burden of Itch;
Figure 4)
• Roflumilast-treated patients also had a significant improvement in quality of life as indicated by the
Dermatology Life Quality Index (DLQI; Figure 5)
44.6%
62.0%
71.0%
15.6%
22.1%
18.5%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Week 2 Week 4 Week 8
Pa
tie
nt
s
(%
)
Roflumilast foam 0.3% (n=173) Vehicle foam (n=96)
P<0.0001
P<0.0001
P<0.0001
100
90
80
70
60
50
40
30
20
10
0
%
o
f P
at
ie
nt
s
(9
5%
C
I)
45.3%
57%
68.2%
11.5%
20.5% 23.1%
0%
1000%
2000%
3000%
4000%
5000%
6000%
7000%
8000%
9000%
10000%
Week 2 Week 4 Week 8
%
o
f P
at
ie
nt
s
(9
5%
C
I)
Roflumilast foam 0.3% (n=165) Vehicle (n=94)
P<0.0001
P<0.0001
P<0.0001
100
90
80
70
60
50
40
30
20
10
0
>70% of patients achieved a SI-NRS 4-point response at Week 8
(A) (B)
More than two-thirds of patients had a ≥4-point
improvement on WI-NRS at Week 8
WI-NRS 4-Point ResponsebSI-NRS 4-Point Responsea
Figure 5. LS Mean Change From Baseline in DLQI
Estimates from an ANCOVA model with country, treatment, baseline S-IGA score category, baseline B-IGA score category, and baseline DLQI score as independent variables.
Intent-to-treat population. ANCOVA: analysis of covariance; B-IGA: Body-Investigator Global Assessment; CfB: change from baseline; DLQI: Dermatology Life Quality Index; LS:
least squares; QoL: quality of life; SE: standard error; S-IGA: Scalp-Investigator Global Assessment.
0.0%
-27.8%
-47.3%
-61.6%
0.0%
17.0%
-2.5%
-17.7%
Baseline Week 2 Week 4 Week 8
0
−20
−40
−60
−80
−120
−100
LS
M
ea
n
%
C
fB
(S
E)
20
40
Overall QoL benefit was higher
with roflumilast than with vehicle
Roflumilast foam 0.3% (n=200)
Vehicle foam (n=104)
P<0.0001
P<0.0001
P<0.0001
0.0%
-42.3%
-50.4%
-60.6%
-16.2%
-26.1% -27.0%
-100%
-80%
-60%
-40%
-20%
0%
Baseline Week 2 Week 4 Week 8
M
ea
n
%
C
fB
(9
5%
C
I)
Roflumilast foam 0.3% (n=200) Vehicle foam (n=104)
0.0%
-39.9%
-49.5%
-59.6%
-18.5%
-24.5% -26.5%
-100%
-80%
-60%
-40%
-20%
0%
Baseline Week 2 Week 4 Week 8
M
ea
n
%
C
fB
(9
5%
C
I)
Roflumilast foam 0.3% (n=200) Vehicle foam (n=104)
Roflumilast treatment resulted in greater reduction in severity of itch
(A) (B)
Burden of itch was reduced to a greater extent with roflumilast
PSD Item 1 (Severity of Itch)a
How severe was your psoriasis-related itching over the past 24 hours?
PSD Item 2 (Burden of Itch)a
How bothered were you by your psoriasis-related itching over the past 24 hours?
0
−20
−40
−60
−80
−100
0
−20
−40
−60
−80
−100
To control for multiple comparisons among the secondary endpoints, a multiplicity procedure was used. Upon successful testing of the primary endpoint, the α was partitioned to test secondary endpoints. Estimates from an ANCOVA model with
country, treatment, baseline S-IGA score category, baseline B-IGA score category, and baseline PSD score as independent variables. Intent-to-treat population. ANCOVA: analysis of covariance; B-IGA: Body-Investigator Global Assessment; CfB: change
from baseline; CI: confidence interval; PSD: Psoriasis Symptom Diary; SE: standard error; S-IGA: Scalp-Investigator Global Assessment.
REFERENCES
1. Chan CS, et al. J Am Acad Dermatol 2009;60:962-971.
2. Elewski B, et al. J Eur Acad Dermatol Venereol
2019;33:1465-1476.
3. Dopytalska K, et al. Reumatologia 2018;56:392-398.
4. Blakely K, Gooderham M. Psoriasis 2016;6:33-40.
5. 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 Christina McManus, PhD, Alligent
Biopharm Consulting LLC, and funded by Arcutis Biotherapeutics, Inc.
Once-Daily Roflumilast Foam 0.3% Improves Severity and Burden of Itch in Patients With �Scalp and Body Psoriasis in a Randomized, Double-blind, Vehicle-Controlled Phase 2b Study
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