PowerPoint Presentation


PRESENTED AT 40TH ANNUAL FALL CLINICAL DERMATOLOGY CONFERENCE, OCTOBER 29–NOVEMBER 1, 2020

Figure 4. Secondary (A) and Exploratory (B) Efficacy Endpoints at Weeks 1 Through 4 

Data presented for intent-to-treat population. Only significant P-values (P<0.05) shown. CI: confidence interval; EASI: Eczema Area and Severity Index; LS: least squares; vIGA-AD: Validated Investigator Global Assessment for Atopic Dermatitis.

Week 1 Week 2 Week 4

Pa
ti

en
ts

, %

vIGA-AD Score of “Clear” or “Almost Clear”(B)

60

50

40

30

20

10

0

EASI Percent Change From Baseline

Figure 2. Absolute EASI Change From Baseline at Week 4 (Primary Endpoint)

Data presented for intent-to-treat population. CI: confidence interval; EASI: Eczema Area and Severity Index; LS: least squares.

Figure 3. Secondary (A, B) and Exploratory (C) Efficacy Endpoints at Week 4 

Data presented for intent-to-treat population. Only significant P-values (P<0.05) shown. CI: confidence interval; EASI: Eczema Area and Severity Index; LS: least squares; vIGA-AD: Validated Investigator Global Assessment for Atopic Dermatitis.

INTRODUCTION
• Majority of patients with atopic dermatitis are treated with topical anti-inflammatory therapy: 

corticosteroids or calcineurin inhibitors, in combination with emollients1

– Side effects and poor adherence limit long-term use of topical corticosteroids
– Topical calcineurin inhibitors may cause local tolerability reactions

• Phosphodiesterase-4 (PDE-4) is the predominant cyclic adenosine monophosphate–degrading 
enzyme in inflammatory cells, including lymphocyte subsets, and has increased activity in 
inflammatory skin disorders like atopic dermatitis2,3

• Roflumilast cream is a highly potent PDE-4 inhibitor with ~25- to >300-fold higher potency than 
other approved PDE-4 inhibitors4

– Roflumilast cream is in phase 3 development for plaque psoriasis5

OBJECTIVE
• To assess the short-term safety and efficacy of once-daily (QD) topical roflumilast cream in 

patients with mild to moderate atopic dermatitis 

METHODS
• Randomized, double-blind, vehicle-controlled, multicenter phase 2 study (ClinicalTrials.gov 

NCT03916081; Figure 1)

• At the early timepoint of 4 weeks, roflumilast cream improved severity of atopic dermatitis as measured by 
absolute change from baseline in Eczema Area and Severity Index (EASI), yet was not statistically significant 
(Figure 2)

• A robust response to vehicle was observed

• Patient cases illustrating improvement in severity of atopic dermatitis with 
roflumilast cream are shown in Figure 5

CONCLUSIONS
• In this small proof-of-concept study, roflumilast cream QD demonstrated efficacy compared 

with vehicle cream in atopic dermatitis 
– Primary endpoint showed a trend toward, but did not reach, statistical significance  
– Statistical significance was reached for other efficacy endpoints 
– Substantial efficacy noted, with 72.3% EASI improvement and >50% of patients achieving 

“clear” or “almost clear” skin on vIGA-AD at Week 4 for roflumilast cream 0.15%
– Continued efficacy through Week 4 was observed
– High response rate with cream vehicle in this study may have been a factor in not reaching 

statistical significance in the primary endpoint
• Roflumilast cream was well-tolerated, with a low rate of application site reactions and no 

signs of local irritation

• Secondary and exploratory endpoints showed significant improvement with roflumilast cream over vehicle at Week 4 (Figure 3)

• Efficacy of roflumilast cream continued to improve through Week 4 (Figure 4)

Safety and Tolerability
• Treatment-emergent adverse events (TEAEs) were uncommon in this study (Table 2)
• Safety and tolerability of roflumilast was similar to vehicle group 
• All TEAEs were mild or moderate 
• Low rates of application-site adverse events 
• No psychiatric TEAEs
• No unintentional weight loss of more than 5%

Statistical Analysis
• The primary endpoint was analyzed with a mixed-effects model for repeated measures, as were 

other continuous endpoints 
• Categorical endpoints were analyzed with a Cochran-Mantel-Haenszel test
• Comparisons were specified at the 0.05 level and were not adjusted for multiplicity

RESULTS
• Overall, patients were recruited from 3 sites in Canada and 19 sites in the United States and 

randomized to roflumilast 0.15% (n=45), roflumilast 0.05% (n=46), or vehicle (n=45) 
• Completion rate was over 90% in all treatment groups
• Baseline characteristics are presented in Table 1

Table 1. Baseline Characteristics
Roflumilast 0.15%

(n=45)
Roflumilast 0.05%

(n=46)
Vehicle
(n=45)

Age, mean (SD), years 38.0 (16.5) 44.3 (17.0) 42.4 (17.6)
Sex, female, n (%) 33 (73.3) 31 (67.4) 29 (64.4)
Race, n (%)

White 24 (53.3) 32 (69.6) 32 (71.1)
Black 14 (31.1) 11 (23.9) 11 (24.4)
Multiple/other 7 (15.6) 3 (6.5) 2 (4.4)

vIGA-AD score, mean (SD) 2.8 (0.4) 2.8 (0.4) 2.8 (0.4)
2 (mild), n (%) 10 (22.2) 11 (23.9) 9 (20.0)
3 (moderate), n (%) 35 (77.8) 35 (76.1) 36 (80.0)

EASI, mean score (SD) 9.5 (4.1) 8.4 (4.1) 9.2 (3.9)
BSA, mean (SD), % 9.6 (6.0) 8.4 (7.1) 10.5 (6.6)
WI-NRS, mean score (SD) 6.6 (2.0) 6.5 (2.0) 7.2 (2.1)

WI-NRS score ≥6, n (%) 32 (71.1) 31 (67.4) 38 (84.4)
Data are presented for safety population. BSA: body surface area; EASI: Eczema Area and Severity Index; SD: standard deviation; 
vIGA-AD: Validated Investigator Global Assessment for Atopic Dermatitis; WI-NRS: Worst Itch Numeric Rating Scale.

Roflumilast cream, a potent PDE-4 inhibitor, represents a potential effective QD topical 
treatment for atopic dermatitis. Favorable safety profile and encouraging efficacy results 

warrant further investigation of roflumilast cream in larger studies over longer times

Figure 1. Study Design

BSA: body surface area; EASI: Eczema Area and Severity Index; QD: once daily; vIGA-AD: Validated Investigator Global Assessment for Atopic 
Dermatitis; WI-NRS: Worst Itch Numeric Rating Scale.

VehicleRoflumilast 0.15%

Baseline

Week 4

vIGA-AD = 3

vIGA-AD = 2
EASI CFB = -77%

vIGA-AD = 3

vIGA-AD = 3
EASI CFB = -27%

REFERENCES
1. Silverberg JI, et al. J Dermatolog Treat 2016;27:568-576. 
2. Bäumer W, et al. Inflamm Allergy Drug Targets 2007;6:17-26. 
3. Guttman-Yassky E, et al. Exp Dermatol 2019;28:3-10.
4. Dong C, et al. J Pharmacol Exp Ther 2016;358:413-422. 
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 Aleksandra Adomas, PhD, CMPP, Touch Scientific, Philadelphia, PA, 

and funded by Arcutis Biotherapeutics, Inc.

DISCLOSURES
MJG, LHK, MZ, ML, SEK, ZDD, LF, TMJ, ES-CP, RB, NB, STG, and RAK: Investigator, consultant, and/or advisory 
board member for Arcutis Biotherapeutics, Inc. ZDD has received grant support from Arcutis Biotherapeutics, 
Inc. HW has a patent application relevant to this work. CM, ME, LN, RCH, MG, and DRB: Employees of Arcutis
Biotherapeutics, Inc. 

Table 2. Summary of AEs

TEAE, n (%)
Roflumilast 0.15%

(n=45)
Roflumilast 0.05%

(n=46)
Vehicle
(n=45)

Patients with

Any TEAE 12 (26.7) 10 (21.7) 6 (13.3)

Any treatment-related TEAE 0 2 (4.3) 2 (4.4)

TEAE leading to study 
discontinuationa

0 1 (2.2) 1 (2.2)

SAEb 0 1 (2.2) 0

Maximum severity of TEAEs

Mild 10 (22.2) 6 (13.0) 5 (11.1)

Moderate 2 (4.4) 4 (8.7) 1 (2.2)

Application site TEAEs

Application site pain 0 1 (2.2) 1 (2.2)

Atopic dermatitis worsening 0 0 1 (2.2)

Skin lacerationc 0 1 (2.2) 0
aRoflumilast 0.05%: moderate application site pain; vehicle: moderate worsening of AD. bRoflumilast 0.05%: mild traumatic spinal cord 
compression that was considered unrelated to the study drug. cUnrelated to the study drug. Data presented for safety population. AE: adverse 
event; SAE: serious adverse event; TEAE: treatment-emergent adverse event.

Figure 5. Patient Cases Representative of the Efficacy of Roflumilast 
Cream 0.15% at Week 4 Compared With Vehicle

CFB: change from baseline; EASI: Eczema Area and Severity Index; vIGA-AD: Validated Investigator Global Assessment for 
Atopic Dermatitis.

Week 1 Week 2 Week 4

LS
 M

ea
n 

Ch
an

ge
 F

ro
m

 B
as

el
in

e,
%

 (9
5%

 C
I)

(A)

0

-10

-20

-30

-40

-50

-60

-70

-80

-90

P=0.040

P=0.035

Vehicle (n=45)Roflumilast 0.15% (n=45) Roflumilast 0.05% (n=46)

Melinda J. Gooderham,1 Leon H. Kircik,2 Matthew Zirwas,3 Mark Lee,4 Steven E. Kempers,5 Zoe D. Draelos,6 Laura Ferris,7 Terry M. Jones,8 Etienne Saint-Cyr Proulx,9 Robert Bissonnette,9
Neal Bhatia,10 Scott T. Guenthner,11 Robert A. Koppel,12 Howard Welgus,13 Charlotte Merritt,13 Meg Elias,13 Lynn Navale,13 Robert C. Higham,13 Michael Droege,13 David R. Berk13
1SKiN Centre for Dermatology, Probity Medical Research and Queen’s University, Peterborough, ON, Canada; 2Icahn 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; 3Dermatologists of the Central States, Probity Medical Research, 
and Ohio University, Bexley, OH, USA; 4Progressive Clinical Research, San Antonio, TX, USA; 5Minnesota Clinical Study Center, Fridley, MN, USA; 6Dermatology Consulting Services, PLLC, High Point, NC, USA; 7University of Pittsburgh, Department of Dermatology, Pittsburgh, PA, USA; 8US Dermatology Partners, Bryan, TX, USA; 9Innovaderm Research, 
Montreal, QC, Canada; 10Therapeutics Clinical Research, San Diego, CA, USA; 11The Indiana Clinical Trials Center, PC, Plainfield, IN, USA; 12Clinical Trials Management, LLC, Metairie, LA, and Tulane University School of Medicine in New Orleans, LA, USA; 13Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA

The Safety and Efficacy of Roflumilast Cream 0.15% and 0.05% in Atopic Dermatitis:                       
Phase 2 Proof-of-Concept Study

Roflumilast
cream

0.15% QD

Roflumilast
cream

0.05% QD

Vehicle
QD

ENDPOINTS
• Primary: EASI change from baseline
• Secondary:

– EASI % change from baseline
– EASI-50 and EASI-75
– BSA
– WI-NRS

• Exploratory:
– vIGA-AD “clear” or “almost clear”
– vIGA-AD “clear” or “almost clear” 

+ ≥2-grade improvement 
• Safety and tolerability

4 weeks

Ra
nd

om
iz

at
io

n

1:1:1

N=136

ELIGIBILITY
• Mild or moderate atopic 

dermatitis (vIGA-AD=2 or 3)
• Age ≥12 years
• 1.5-35% BSA
• EASI >5

Vehicle (n=45)Roflumilast 0.15% (n=45) Roflumilast 0.05% (n=46)

Week 4

Pa
ti

en
ts

, %
 (9

5%
 C

I)

100
90
80
70
60
50
40

20
10

0

30
52.3

59.1

31.1

P=0.009
P=0.045

Week 4

LS
 M

ea
n 

Ch
an

ge
 F

ro
m

 B
as

el
in

e,
%

 (9
5%

 C
I) -72.3

-69.4
-55.8

P=0.049

0

-10

-20

-30

-40

-50

-60

-70

-80

-90

EASI-75 Responder Rate vIGA-AD Score of “Clear” 
or “Almost Clear”

(A) (B) (C)

Week 4

Pa
ti

en
ts

, %
 (9

5%
 C

I)

52.3 50.0
31.1

P=0.040
100

90
80
70
60
50
40

20
10

0

30

EASI Percent 
Change From Baseline

P=0.049
Scan QR Code for 
a digital copy of 

this poster

Vehicle (n=45)Roflumilast 0.15% (n=45) Roflumilast 0.05% (n=46)

-6.4 -6.0
-4.8

-8

-7

-6

-5

-4

-3

-2

-1

0
Week 4

LS
 M

ea
n 

Ch
an

ge
 F

ro
m

 B
as

el
in

e 
(9

5%
 C

I)

P=0.356
P=0.097


	Slide Number 1
















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