PowerPoint Presentation


PRESENTED AT THE WINTER CLINICAL DERMATOLOGY CONFERENCE - HAWAII® (WCH23), JANUARY 13–18, 2023, KOHALA COAST, HI, USA

Figure 2. Patient Disposition

aTwo patients withdrew from the study due to “other” reasons, which was COVID-19 disruption.

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.

3. Stein Gold LS, et al. Poster presented at: Innovations 
in Dermatology; March 16-20, 2021; Virtual.

INTRODUCTION
• Roflumilast cream, a phosphodiesterase 4 (PDE4) inhibitor that is more potent than other PDE4 

inhibitors,1 was recently approved as a once-daily, nonsteroidal, topical treatment for psoriasis, including 
intertriginous areas, in patients 12 years of age and older with no limitations on duration of use

• In a phase 2b, randomized, double-blind, 12-week trial of 331 adults with chronic plaque psoriasis, 
roflumilast cream once daily was superior to vehicle cream and was well tolerated2

• The durability of response was assessed in a multicenter, open-label, 52-week study conducted to 
evaluate long-term safety of roflumilast 0.3% cream in patients with chronic plaque psoriasis

METHODS
• This multicenter, open-label, single-arm, long-term, phase 2 safety trial was conducted at 30 centers in 

the United States and Canada 

• Two cohorts of patients were enrolled: Cohort 1 patients were those who completed the phase 2b trial 
through Week 12, whereas Cohort 2 eligible patients were newly enrolled (treatment-naïve; Figure 1)

CONCLUSIONS
• In this phase 2 long-term safety study, roflumilast cream 0.3%, a once-daily, nonsteroidal 

topical PDE4 inhibitor, was well-tolerated with a safety profile consistent with the parent 
phase 2b trial (Trial 201) 

– Rates of discontinuations due to AEs and lack of efficacy were low

– No tachyphylaxis occurred and efficacy was consistent over time (IGA Success, IGA 0/1, 
and percentage change from baseline in BSA and PASI)

– Of the 185 patients who achieved IGA Clear/Almost Clear during the open-label trial, 
the median durability of IGA of Clear/Almost Clear was 10 months (40.1 weeks)

RESULTS
• Patient demographics and clinical characteristics at baseline were similar across cohorts (Table 1) 

• Of the 249 subjects who completed trial 201 from sites that participated in this open-label trial, 230 
(92.4%) of them enrolled into this study

• 244 (73.5%) completed the 202 trial of the 332 patients enrolled across cohort 1 (n=230) and cohort 2 
(n=102; Figure 2)

• Percentages of patients achieving Investigator Global Assessment (IGA) Success and an IGA of Clear or 
Almost Clear were consistent over time (Figure 3)

Mark Lebwohl,1 Linda Stein Gold,2 Melinda J. Gooderham,3 Kim A. Papp,4 Laura K. Ferris,5 David N. Adam,6 H. Chih-ho Hong,7 Leon H. Kircik,8 Matthew Zirwas,9 Patrick Burnett,10 Robert Higham,10

David Krupa,10 David Berk10

1Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Henry Ford Medical Center, Detroit, MI, USA; 3SkiN Centre for Dermatology, Probity Medical Research and Queen’s University, Peterborough, ON, Canada; 4Probity Medical Research and K Papp Clinical Research, 
Waterloo, ON, Canada; 5University of Pittsburgh, Department of Dermatology, Pittsburgh, PA, USA; 6CCA Medical Research, Probity Medical Research and Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 7Probity Medical Research and University of 
British Columbia, Department of Dermatology and Skin Science, Surrey, BC, Canada; 8Icahn 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; 
9Dermatologists of the Central States, Probity Medical Research, and Ohio University, Bexley, OH, USA; 10Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA

Durability of Efficacy and Safety of Roflumilast Cream 0.3% in Adults With 
Chronic Plaque Psoriasis From a 52-Week, Phase 2 Open-Label Safety Trial

Figure 1. Study Design

aExcludes 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.

Table 1. Baseline Disease Characteristics

Roflumilast 0.15% and 0.3% →
Roflumilast 0.3% (n=164)

Cohort 2 and Vehicle → 
Roflumilast 0.3% (n=168)

Overall Total 
(N=332)

BSA, mean % 6.6 6.0 6.3

PASI, mean 7.2 6.3 7.1

IGA score, n (%)

1 (almost clear) 0 (0.0) 8 (4.8) 8 (2.4)

2 (mild) 28 (17.1) 40 (23.8) 68 (20.5)

3 (moderate) 124 (75.6) 110 (65.5) 234 (70.5)

4 (severe) 12 (7.3) 10 (6.0) 22 (6.6)

Intertriginous involvement (I-IGA ≥2)

I-IGA, n (%)

2 (mild) 14 (8.5) 17 (10.1) 31 (9.3)

3 (moderate) 11 (6.7) 18 (10.7) 29 (8.7)

4 (severe) 1 (0.6) 1 (0.6) 2 (0.6)
Baseline is defined as the last observation prior to the first dose of roflumilast cream in the parent trial (Cohort 1 roflumilast 0.3% and roflumilast 0.15% groups) or the current trial 
(Cohort 1 vehicle group and Cohort 2).
BSA: body surface area; IGA: Investigator Global Assessment; I-IGA: Intertriginous-IGA; PASI: Psoriasis Area Severity Index.

Table 2. Summary of AEs (Safety Population) 

TEAE, n (%)
Roflumilast 0.15% and 0.3% → 

Roflumilast 0.3% (n=164)
Cohort 2 and Vehicle → 

Roflumilast 0.3% (n=168)
Overall
(N=332)

Patients with any TEAE 79 (48.2) 85 (50.6) 164 (49.4)

Patients with any treatment-
related TEAE

4 (1.7) 5 (4.9) 9 (2.7)

Patients with any SAE 8 (4.9) 4 (2.4) 12 (3.6)

Any treatment-related SAE 0 (0) 0 (0) 0 (0)

Patients who discontinued study 
drug due to AE

8 (4.9) 5 (3.0) 13 (3.9)

Treatment-emergent adverse event 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 (%)
Roflumilast 0.15% and 0.3% → 

Roflumilast 0.3% (n=164)
Cohort 2 and Vehicle → 

Roflumilast 0.3% (n=168)
Overall
(N=332)

Upper respiratory tract infection/
viral URTI

10 (6.1) 12 (7.1) 22 (6.6)

Nasopharyngitis 6 (3.7) 6 (3.6) 12 (3.6)

Urinary tract infection 5 (3.0) 6 (3.6) 11 (3.3)

Sinusitis 3 (1.8) 5 (3.0) 8 (2.4)
AE: adverse event; TEAE: treatment-emergent adverse event; URTI: upper respiratory tract infection.

Figure 7. Mean Percent BSA Affected 

Observed data. No imputations of missing values.
Baseline is defined as the last observation prior to the first dose of Roflumilast Cream in the ARQ-151-202 study.
BSA: body surface area; SD: standard deviation.

2.6 2.3 2.2 2.2

2.2

3.9

2.6 2.4 2.2

2.2

0
1
2
3
4
5
6
7
8
9

10

Week 4 Week 12 Week 24 Week 36 Week 52

M
e

a
n

 P
A

S
I 

S
co

re

Roflumilast 0.15% and 0.3% → Roflumilast 0.3% (n=164)

Cohort 2 and Vehicle → Roflumilast 0.3% (n=168)

Roflumilast → Roflumilast 162 150 136 128 119
Vehicle/Naive → Roflumilast 162 154 140 129 127

201 Parent trial baseline mean (SD) BSA:  6.15 (3.9)
Cohort 2 baseline mean (SD) BSA:  6.6 (5.3)

Figure 4. Percentage of Patients With I-IGA Success Over Time3,a

aCohort 1 not shown because I-IGA added as study amendment and numbers of patients evaluated are very small at each timepoint. 
I-IGA: intertriginous Investigator Global Assessment; I-IGA Success: I-IGA score of Clear or Almost Clear plus 2-grade improvement from baseline.

42.9

60.0 60.0 56.3
66.7

0

20

40

60

80

100

Week 4
(n=21)

Week 12
(n=20)

Week 24
(n=20)

Week 36
(n=16)

Week 52
(n=15)

P
a

ti
e

n
ts

, 
%

Roflumilast cream 0.3% 
n=81

Roflumilast cream 0.15% 
n=83

Vehicle cream 
n=66

Completed 
n=244 (73.5%)

Roflumilast cream 0.3% 
n=102

Discontinued: 88 (26.5%)
Withdrew: 36 (10.8%) 
Lost to follow-up: 34 (10.2%)
Adverse event: 13 (3.9%)
Lack of efficacy: 3 (0.9%)
Other: 2 (0.6%)a

Cohort 1 Cohort 2

Enrolled
N=332

Figure 3. Percentage of Patients Achieving (A) IGA Success and (B) Clear or Almost Clear

As observed. No imputation of missing values. 
Baseline is defined as the last observation prior to the first dose of roflumilast cream in the parent trial (Cohort 1 roflumilast 0.3% and roflumilast 0.15% groups) or the current trial (Cohort 1 vehicle group and Cohort 2).
IGA: Investigator Global Assessment; IGA Success = IGA score of Clear or Almost Clear plus two-grade improvement from baseline.

32.7
36.7 36.0

30.5
35.3

12.9

36.1
29.3

32.0
37.5

0

10

20

30

40

50

60

70

80

90

100

Week 4 Week 12 Week 24 Week 36 Week 52

P
a

ti
e

n
ts

, 
%

Roflumilast 0.15% and 0.3% → Roflumilast 0.3% (n=164)

Cohort 2 and Vehicle → Roflumilast 0.3% (n=168)

Roflumilast → Roflumilast 162 150 136 128 119
Vehicle/Naive → Roflumilast 163 154 140 129 127

A

40.7

45.3

44.9

39.1 42.0

22.6

48.3

39.1

44.3 47.5

0

10

20

30

40

50

60

70

80

90

100

Week 4 Week 12 Week 24 Week 36 Week 52

P
a

ti
e

n
ts

, 
%

Roflumilast 0.15% and 0.3% → Roflumilast 0.3% (n=164)

Cohort 2 and Vehicle → Roflumilast 0.3% (n=168)

Roflumilast → Roflumilast 162 150 136 128 119
Vehicle/Naive → Roflumilast 163 154 140 129 127

B

Figure 6. Mean PASI Score

Observed data. No imputation of missing values.
PASI assessment was added as an amendment to the trial.
PASI: Psoriasis Area and Severity Index; SD: standard deviation.

3.37
2.53 2.56 2.57

2.74
3.34

2.5 2.49 2.6

2.37

0
1
2
3
4
5
6
7
8
9

10

Week 4 Week 12 Week 24 Week 36 Week 52

M
e

a
n

 P
A

S
I 

S
co

re

Roflumilast 0.15% and 0.3% → Roflumilast 0.3% (n=164)

Cohort 2 and Vehicle → Roflumilast 0.3% (n=168)

Roflumilast → Roflumilast 17 65 111 128 119
Vehicle/Naive → Roflumilast 101 122 129 129 127

201 Parent trial baseline mean (SD) PASI:  7.1 (3.3)
Cohort 2 baseline mean (SD) PASI: 6.8 (3.3)

Figure 5. Median Duration of IGA of Clear or Almost Clear

Duration of IGA 0/1: the time from the first observation of IGA 0/1 to the first subsequent time a patient’s IGA is not IGA 0/1.
Patients who received vehicle in parent study and rolled over into Study 202 with a 0/1 assessment are excluded from this analysis (N=324).
IGA: Investigator Global Assessment.

~57.1% (n=185) of patients achieved IGA 0/1 during the trial;
patients have a 50% probability of a duration of IGA of Clear 

or Almost Clear of more than 10 months (40.1 weeks)

Duration of IGA Clear or Almost Clear (Weeks)

0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0

P
ro

b
a

b
il

it
y

 I
G

A
 C

le
a

r
o

r
A

lm
o

st
 C

le
a

r

4 12 20 28 360 8 16 24 32 44 56 6440 48 6052

Censored

170 138 114 93 69185 166 123 101 82 41 5 063 37 28At risk

Roflumilast Cream Phase 2b
(Trial #201; NCT03638258)2

Roflumilast Cream Phase 2 Long-term Safety 
(Trial #202; NCT03764475)

Eligibility

• Diagnosis of at 
least mild 
plaque psoriasis

• Age ≥18 years

• 2-20% BSAa

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
• Intertriginous-IGA 

clear or almost 
clear

• PASI
• BSA

12 weeks

R
a

n
d

o
m

iz
a

ti
o

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
(n=230)

52 weeks

Cohort 2 (Naïve)
Roflumilast cream 

0.3% QD
(n=102)

Completed
Trial #201 
through

12 weeks

Patients could stop 
applying treatment 

to lesions that cleared
Patients could completely 

stop treatment when 
PASI and IGA = 0 following 

an office visit
Treatment could be resumed 

when patient-observed 
psoriasis recurred

DISCLOSURES
ML, LSG, MJG, KAP, LKF, DNA, HCH, LHK, and MZ are investigators and/or consultants for Arcutis Biotherapeutics, Inc. and received 
grants/research funding and/or honoraria; PB, RH, DK, and DB are employees of Arcutis Biotherapeutics, Inc. Additional disclosures provided 
on request.

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.

• Among patients with intertriginous area involvement, roflumilast cream provided consistent 
improvement of Intertriginous-Investigator Global Assessment (I-IGA; Figure 4)

• Median duration of IGA of Clear or Almost Clear was 10 months (Figure 5)

• A 60.5% mean improvement from baseline in Psoriasis Area Severity Index (PASI) and 60.1% 
mean improvement from baseline in body surface area (BSA) affected were observed at Week 
12 (Figures 6 and 7)

– Results were consistent through Week 52 

– Median BSA at Week 52 was 1.0%

• Safety was consistent with the parent trial (Tables 2 and 3)

• 94% of adverse events (AEs) were rated mild or moderate in severity 

• 97% of AEs were unrelated or unlikely to be related to treatment as determined by the 
investigator

• ≥97% of patients had no evidence of irritation per investigator local tolerability assessment at 
each visit (Figure 8)

Figure 8. Percentage of Patients With Investigator-rated Tolerability Score >0

1.2% 0.6% 1.0% 0.4% 0.0% 0.0%
0

10

20

30

40

50

60

70

80

90

100

Baseline Week 4 Week 12 Week 24 Week 36 Week 52

P
a

ti
e

n
ts

, 
%

Overall (N=332)
Scale for investigator-rated local tolerability (0–7)

0 = no evidence of irritation

1 = minimal erythema, barely perceptible 

2 = definite erythema, readily visible; minimal edema or minimal 
papular response

3 = erythema and papules

4 = definite edema

5 = erythema, edema and papules

6 = vesicular eruption

7 = strong reaction spreading beyond application site 

n=331 n=324 n=304 n=276 n=255 n=238


	Slide 1: Durability of Efficacy and Safety of Roflumilast Cream 0.3% in Adults With Chronic Plaque Psoriasis From a 52-Week, Phase 2 Open-Label Safety Trial