Poster presented at the 38th Annual Fall Clinical Dermatology Conference; Oct 17-20, 2019; Las Vegas, NV
Lebrikizumab, a High-Affinity IL-13 Inhibitor, Improves Clinical Manifestations in
Moderate-to-Severe Atopic Dermatitis: Primary Results From a Randomized,
Double-Blinded, Placebo-Controlled, Dose-Ranging, Phase 2b Study
E. Guttman-Yassky,1 A. Blauvelt,2 L. F. Eichenfield,3 A. Paller,4 A. Armstrong,5 J. Drew,6 R. Gopalan,6 E. Simpson7
1Icahn School of Medicine at Mount Sinai, New York, NY; 2Oregon Medical Research Center, Portland, OR; 3University of California and Rady Children’s Hospital, San Diego, CA; 4Northwestern University Feinberg School of Medicine, Chicago, IL; 5Keck School of Medicine at University of
Southern California, Los Angeles, CA; 6Dermira, Inc., Menlo Park, CA; 7Oregon Health and Science University, Portland, OR
INTRODUCTION
• Moderate-to-severe atopic dermatitis (AD) is a prevalent, debilitating
condition characterized by a broad range of clinical manifestations,
including skin lesions and intense, persistent pruritus that can have a
significant, multi-dimensional impact on quality of life1,2
• Interleukin (IL)-13 is a central pathogenic mediator driving multiple features
of AD pathophysiology underlying the range of clinical manifestations3-5
• Lebrikizumab (LEB) is a novel, high-affinity monoclonal antibody
targeting IL-13 that selectively prevents formation of the IL-13Rα1/IL-
4Rα heterodimer receptor signaling complex while leaving endogenous
regulation of IL-13 intact
OBJECTIVE
• To report the efficacy and safety of LEB from a randomized,
double-blinded, placebo-controlled, dose-ranging, phase 2b study in
adults with moderate-to-severe AD (NCT03443024)
METHODS
Study Design
• This phase 2b study consisted of a 16-week treatment period with 16-week
safety follow-up (Figure 1)
• Patients were randomized 3:3:3:2 to subcutaneous LEB 125 mg every
4 weeks (Q4W; 250 mg loading dose [LD]), 250 mg Q4W (500 mg
LD), 250 mg every 2 weeks (Q2W; 500 mg LD at Weeks 0 and 2), or
placebo Q2W for 16 weeks
• Patients requiring rescue therapy were allowed to use topical
corticosteroids (TCS) for as brief a period as possible and could remain
in the study; those requiring systemic rescue therapy were discontinued
Figure 1. Study Design
Week 0 Week 4 Week 8 Week 12 Week 16 Week 32
Placebo Q2W (n=52)
LEB 250 mg Q2W (n=75)
500 mg LD
Wk 0 & 2
LEB 250 mg Q4W (n=80)
500 mg LD
Wk 0
LEB 125 mg Q4W (n=73)
250 mg LD
Wk 0
Safety follow-up
to Week 32
Screening (≤30 days) Randomized, Double-Blind Treatmenta
Primary Endpoint: Percent change in
EASI from Baseline at Week 16
3:3:3:2
Randomization
N=280
aPatients were seen every two weeks and received all study drug injections in the clinic
EASI, Eczema Area and Severity Index; LD, loading dose; Q2W, every 2 weeks; Q4W, every 4 weeks;
Wk, week
Study Patients
• Eligible patients were ≥18 years, with Eczema Area Severity Index (EASI)
≥16, Investigator’s Global Assessment (IGA) score ≥3 (5-point scale), ≥10%
body surface area (BSA) affected, and chronic AD for ≥1 year for which
topical treatment provided inadequate control or was medically inadvisable
• Patients were excluded for having had treatment with TCS or topical
calcineurin inhibitors (TCI) within 1 week prior to Baseline
• Prior biologics were allowed if washout occurred as follows relative
to Baseline: dupilumab within 3 months, cell-depleting (eg, rituximab)
within 6 months, other biologics within 5 half-lives or 16 weeks, and
investigational drug within 8 weeks or 5 half-lives
Efficacy and Safety Assessments
• The primary endpoint was percent change in EASI from Baseline at Week 16
• Secondary endpoints included proportion of patients achieving EASI50,
EASI75, EASI90, IGA score of 0 or 1 (IGA 0/1), pruritus numeric rating
scale (NRS; 11-point scale [0 to 10]) change ≥4 points, and percent
change in pruritus NRS from Baseline at Week 16
• Visits occurred biweekly through Week 16, and at Weeks 20 and 24;
a safety follow-up visit occurred at Week 24, with telephone follow-up
at Week 32; safety assessments included treatment-emergent adverse
events (TEAEs)
Statistical Analyses
• Efficacy analyses used the modified intent-to-treat (mITT) population
(all patients who were randomized and received study drug)
• Safety analyses used the safety population (those randomized who
received ≥1 dose of study drug)
• Missing data through Week 16 were imputed using Markov chain Monte
Carlo (MCMC) multiple imputation, with no imputation for missing pruritus
data (prespecified)
– Data for patients requiring topical rescue were included if available;
data for those requiring systemic rescue were considered missing from
the time of withdrawal
– A post hoc analysis was performed for pruritus, whereby missing data
were imputed using MCMC imputation
• Statistical comparisons were performed between LEB and placebo (and
not between LEB groups)
RESULTS
• A total of 73, 80, 75, and 52 patients were randomized to LEB 125 mg
Q4W, 250 mg Q4W, 250 mg Q2W, and placebo, respectively
• Week 16 completion rates were similar across all LEB groups and greater
than placebo (Figure 2)
Figure 2. Patient Disposition
Screened
N=424
Randomized
n=280
Placebo Q2W
n=52
n=23
(44.2%)
Discontinued 29
Adverse event 1
Lost to follow-up 4
Pregnancy 1
Protocol deviation 2
Withdrawal by patient 20
Physician decision 1
Other 0
LEB 125 mg Q4W
n=73
n=58
(79.5%)
Discontinued 15
Adverse event 2
Lost to follow-up 6
Pregnancy 0
Protocol deviation 0
Withdrawal by patient 6
Physician decision 0
Other 1
LEB 250 mg Q4W
n=80
n=62
(77.5%)
Discontinued 18
Adverse event 3
Lost to follow-up 5
Pregnancy 0
Protocol deviation 0
Withdrawal by patient 7
Physician decision 2
Other 1
LEB 250 mg Q2W
n=75
n=58
(77.3%)
Discontinued 17
Adverse event 3
Lost to follow-up 6
Pregnancy 0
Protocol deviation 0
Withdrawal by patient 8
Physician decision 0
Other 0
Completed
Week 16
Percentages are based on the number of randomized subjects; one patient who was randomized in
error was not included in the figure
Q2W, every 2 weeks; Q4W, every 4 weeks
• Patient demographics and Baseline disease characteristics were well matched across groups (Table 1)
•
Table 1. Baseline Demographics and Disease Characteristics (mITT Population)
Placebo Q2W
n=52
LEB 125 mg Q4W
n=73
LEB 250 mg Q4W
n=80
LEB 250 mg Q2W
n=75
Baseline Demographics
Age, mean (SD), years 42.2 (18.2) 36.7 (16.5) 40.2 (17.9) 38.9 (17.4)
Male, no. (%) 28 (53.8) 27 (37.0) 33 (41.3) 26 (34.7)
Race, no. (%)
White 26 (50.0) 37 (50.7) 42 (52.5) 40 (53.3)
Black or African American 16 (30.8) 26 (35.6) 28 (35.0) 23 (30.7)
American Indian or Alaska Native 0 1 (1.4) 1 (1.3) 1 (1.3)
Asian 6 (11.5) 8 (11.0) 7 (8.8) 6 (8.0)
Multiple/Other 4 (7.7) 1 (1.4) 2 (2.5) 5 (6.7)
Body mass index, mean (SD), kg/m2 29.7 (8.0) 30.1 (7.7) 29.2 (6.9) 28.1 (6.4)
Baseline Disease Characteristics
Disease duration, mean (SD), years 24.4 (17.4) 22.8 (15.4) 23.3 (16.7)b 22.1 (17.2)
EASI, mean (SD) 28.9 (11.8) 29.9 (13.5) 26.2 (10.1) 25.5 (11.2)
IGA, no. (%)
3, moderate 32 (61.5) 43 (58.9) 54 (67.5) 53 (70.7)
4, severe 20 (38.5) 30 (41.1) 26 (32.5) 22 (29.3)
BSA involvement, mean (SD), percent 46.5 (22.7) 45.5 (24.5) 41.1 (20.9) 39.4 (21.5)
Pruritus NRS score,a mean (SD) 7.4 (2.4) 7.6 (2.0) 7.1 (2.4) 7.6 (1.9)
aPlacebo Q2W, n=49; LEB 125 mg Q4W, n=68; LEB 250 mg Q4W, n=77; LEB 250 mg Q2W, n=69; bn=79
Percentages are based on the number of patients in the modified intent-to-treat (mITT) population with a non-missing response
BMI, body mass index; BSA, body surface area; EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment (5-point scale); NRS, numeric rating scale; Q2W, every 2 weeks; Q4W, every 4 weeks;
SD, standard deviation
• Rescue medication was infrequently required in LEB-treated patients (LEB 125 mg Q4W: 12.3%; 250 mg Q4W: 12.5%; 250 mg Q2W: 13.3%; placebo: 34.6%)
• Topical medication was used by 28.8% of placebo- versus 12.3%, 3.8%, and 8.0% of LEB 125 mg Q4W, 250 mg Q4W, and 250 mg Q2W-treated patients, respectively
• Mean duration of topical medication use was 8 days for placebo versus 4.9, 1.0, 2.5 days for LEB 125 mg Q4W, 250 mg Q4W, and 250 mg Q2W, respectively
• These findings suggest that TCS use would not have confounded study results
Primary Endpoint
• All LEB groups showed dose-dependent, statistically significant improvement in the primary endpoint versus placebo at Week 16 (least squares mean percent
change in EASI: LEB 125 mg Q4W [-62.3%; P<0.05], 250 mg Q4W [-69.2%, P<0.01], 250 mg Q2W [-72.1%, P<0.001] versus placebo [ 41.1%]; (Figure 3)
Figure 3. Percent Change in EASI (mITT Population)
Placebo Q2W
n=52
LEB 125 mg Q4W
n=73
LEB 250 mg Q4W
n=80
LEB 250 mg Q2W
n=75
-41.1
-62.3
* -69.2
**
-72.1
***
0
-20
-40
-60
-80
-100LS
M
ea
n
C
ha
ng
e
fr
om
B
as
el
in
e
(%
)
At Week 16
(Primary Endpoint)
0
-20
-40
-60
-80
-100M
ea
n
C
ha
ng
e
fr
om
B
as
el
in
e
(%
)
To Week 16
4 8 12 160
Placebo Q2W (n=52)
LEB 125 mg Q4W (n=73)
LEB 250 mg Q4W (n=80)
LEB 250 mg Q2W (n=75)
A. B.
-25.4
-31.3 -34.0
-40.6-42.4
-53.9
-62.5 -61.5*
0
-46.5
-61.2
-64.7 -69.7**
-50.4
-64.1
-73.5 -72.8***
*P<0.05, **P<0.01, and ***P<0.001 versus placebo from least squares mean values and an analysis of covariance with a factor of treatment group and corresponding Baseline EASI score as a covariate; statistical
comparison at Week 16 only
Post-Baseline up through Week 16 visit summary statistics represent average values, obtained by averaging the summary statistics generated from each imputed dataset
EASI, Eczema Area and Severity Index; LS, least squares; Q2W, every 2 weeks; Q4W, every 4 weeks
Secondary Endpoints
• A greater proportion of LEB- versus placebo-treated patients achieved EASI50, EASI75, EASI90, and IGA 0/1 at Week 16, with statistically significant
improvements seen with LEB 250 mg Q2W and Q4W (Figure 4)
Figure 4. Secondary Endpoints To Week 16 (mITT Population)
A.
Placebo Q4W (n=52) LEB 125 mg Q4W (n=73) LEB 250 mg Q4W (n=80) LEB 250 mg Q2W (n=75)
0
20
40
60
80
100
0 4 8 12
P
at
ie
nt
s
(%
)
EASI50 EASI75 EASI90 IGA 0/1
16
Week
**77.0
B.
0
20
40
60
80
100
0 4 8 12
P
at
ie
nt
s
(%
)
16
Week
C.
0
20
40
60
80
100
0 4 8 12
P
at
ie
nt
s
(%
)
16
Week
D.
0
20
40
60
80
100
0 4 8 12
P
at
ie
nt
s
(%
)
16
Week
45.8
***81.0
66.4
**56.1
24.3
***60.6
43.3
48.3
16.6
66.9
43.8
7.6
0.5
14.2
3.7
26.0
4.0
29.8
17.3
28.4
5.2
36.4
20.5
24.0
4.8
31.3
14.7 29.9
3.4
42.2
22.1
10.0
0.1
13.9
3.1
38.5
16.7
45.5
30.8
23.4
2.7
30.4
16.7
74.2
34.9
83.1
68.7
68.7
34.8
69.6
57.8
45.2
26.8
52.6
41.9
**36.1
11.4
***44.0
26.1
*33.7
15.3
**44.6
26.6
*P<0.05, **P<0.01, and ***P<0.001 versus placebo from pairwise Cochran-Mantel-Haenszel tests
Post-Baseline up through the Week 16 visit summary statistics represent average values, obtained by averaging the summary statistics generated from each imputed dataset
EASI50/75/90, ≥50%/75%/90% improvement from Baseline in Eczema Area and Severity Index; IGA 0/1, score of 0 ‘clear’ or 1 ‘almost clear’ in investigator global assessment (5-point scale) from Baseline; Q2W, every 2
weeks; Q4W, every 4 weeks
Patient-Assessed Pruritus
• A greater proportion of LEB- versus placebo-treated patients achieved pruritus NRS change ≥4 points at Week 16; dose-dependent, statistically significant
improvement was also seen in LEB- versus placebo-treated patients for the least squares mean percent change in pruritus NRS from Baseline (Figure 5)
Figure 5. Pruritus NRS At Week 16 (mITT Population)
Change ≥4 Points Percent Change from Baseline
27.3
0
20
40
60
80
100
P
at
ie
nt
s
(%
)
Placebo Q2W LEB 125 mg Q4W LEB 250 mg Q4W LEB 250 mg Q2W
A. B.
22
39.3
52n:
41.8
55
43.5
73
47.4
57
46.2
80
70.0
50
67.2
75
No imputation (observed cases)
MCMC imputation
4.3
-100
-60
-40
-20
0
20
LS
M
ea
n
C
ha
ng
e
fr
om
B
as
el
in
e
(%
)
Placebo Q2W LEB 125 mg Q4W LEB 250 mg Q4W LEB 250 mg Q2W
22
-4.6
52n:
-35.9
55
-36.5
73
-49.6
56
-46.4
80
-60.6
50
-58.5
75
-80 No imputation (observed cases)
MCMC imputation
***
**
***
** **
**
*** ***
**P<0.01 and ***P<0.001 versus placebo; panel A: from pairwise Cochran-Mantel-Haenszel tests; panel B: from an analysis of covariance with a factor of treatment group and corresponding Baseline pruritus NRS as the covariate
LS, least squares; MCMC, Markov chain Monte Carlo; NRS, numeric rating scale; Q2W, every 2 weeks; Q4W, every 4 weeks
• Improvements in pruritus NRS were seen to Week 16 (Figure 6)
Figure 6. Pruritus NRS To Week 16 (mITT Population; Observed Cases)
-4.7
-29.6
-21.9
-25.2
-100
-40
-20
0
20
0 2 4 6 8 10 12 14
M
ea
n
C
ha
ng
e
fr
om
B
as
el
in
e
(%
)
Percent Change from BaselineChange ≥4 Points
13.2
27.5
37.1
39.3
28.6
16.7 19.0
27.321.1
32.7
34.0
42.3 51.0
44.7 46.7 41.8
19.7
30.9
46.6
50.9 50.0 57.1 56.8 47.4
31.7
51.9 51.9
58.5 61.8
63.3
68.2
***
70.0
0
20
40
60
80
100
0 2 4 6 8 10 12 14 16
P
at
ie
nt
s
(%
)
Week
Week
B.A.
-80
-60
16
-25.4
-31.3
-34.4
-38.8
-27.7
-32.0
-45.0
-53.0
-21.7
-39.6
-48.6
-45.7
-22.4
-31.3
-44.5
-57.1
-13.3
-41.2
-50.9
-60.1
-15.8
-41.9
-52.3
-63.7
6.8
**
-36.9
***-48.6
***
-61.8
Placebo Q2W
LEB 125 mg Q4W
LEB 250 mg Q4W
LEB 250 mg Q2W
Placebo Q2W
LEB 125 mg Q4W
LEB 250 mg Q4W
LEB 250 mg Q2W
**P<0.01 and ***P<0.001 versus placebo; panel A: from pairwise Cochran-Mantel-Haenszel tests; panel B: from LS mean and an analysis of covariance with a factor of treatment group and corresponding Baseline pruritus
NRS as the covariate
Patient numbers fluctuate at each week as these are observed data
LS, least squares; NRS, numeric rating scale; Q2W, every 2 weeks; Q4W, every 4 weeks
• Differences in the proportions of patients achieving pruritus NRS change ≥4 points were seen by Day 2: 6.3%, 5.6%, 15.3% of LEB 125 mg Q4W, 250 mg
Q4W, 250 mg Q2W versus 4.5% of placebo-treated patients, respectively
Safety
• TEAEs were reported in 57.5%, 48.8%, 61.3% of LEB 125 mg Q4W, 250 mg Q4W, 250 mg Q2W versus 46.2% of placebo-treated patients, respectively
(Table 2); most were mild or moderate in severity and did not lead to discontinuation
• Rates of serious TEAEs were low in all treatment groups, and none were related to treatment
• TEAEs reported in ≥5% in any LEB group were upper respiratory tract infection, nasopharyngitis, fatigue, headache, and injection site pain
• Low rates of conjunctivitis were observed across doses: 1.4%, 3.8%, 2.7% of LEB 125 mg Q4W, 250 mg Q4W, 250 mg Q2W versus 0% of placebo-treated
patients, respectively
• A similar rate of herpes infections was reported in LEB groups versus placebo: 2.7%, 5.0%, 2.7% of LEB 125 mg Q4W, 250 mg Q4W, 250 mg Q2W versus
3.8% of placebo-treated patients, respectively
Table 2. Summary of Treatment-Emergent Adverse Events (Safety Population)
Placebo Q2W
n=52
LEB 125 mg Q4W
n=73
LEB 250 mg Q4W
n=80
LEB 250 mg Q2W
n=75
Patients reporting ≥1 TEAE, n (%) 24 (46.2) 42 (57.5) 39 (48.8) 46 (61.3)
Patients reporting ≥1 serious TEAE , n (%) 2 (3.8) 2 (2.7) 0 2 (2.7)
Number of serious TEAEs, no. 3 2 0 2
Deaths, n (%) 0 0 0 0
Patients who discontinued study due to
TEAE, n (%) 1 (1.9) 2 (2.7) 4 (5.0) 3 (4.0)
Common TEAEs reported in ≥5% in any LEB treatment group,a n (%)
Upper respiratory tract infection 3 (5.8) 6 (8.2) 9 (11.3) 2 (2.7)
Nasopharyngitis 2 (3.8) 4 (5.5) 2 (2.5) 9 (12.0)
Headache 3 (5.8) 3 (4.1) 1 (1.3) 4 (5.3)
Injection site pain 1 (1.9) 0 3 (3.8) 4 (5.3)
Fatigue 0 0 4 (5.0) 0
TEAEs of clinical interest, n (%)
Injection site reactionsb 1 (1.9) 2 (2.7) 4 (5.0) 7 (9.3)
Herpes viral infectionsc 2 (3.8) 2 (2.7) 4 (5.0) 2 (2.7)
Conjunctivitisd 0 1 (1.4) 3 (3.8) 2 (2.7)
aMedDRA Version 20.1 preferred terms; bIncludes MedDRA preferred terms for injection site-related AEs, including injection site pain, erythema, pruritus, edema, swelling, rash, dermatitis, infection, and reaction; cIncludes
MedDRA preferred terms oral herpes, herpes zoster, genital herpes, herpes simplex, and eczema herpeticum; dIncludes MedDRA preferred terms conjunctivitis, conjunctivitis bacterial, and conjunctivitis allergic
TEAEs are those with an onset on or after the date of first study drug injection; patients may have reported ≥1 preferred term
Q2W, every 2 weeks; Q4W, every 4 weeks; TEAE, treatment-emergent adverse event
CONCLUSIONS
• In this phase 2b, placebo-controlled study, all LEB groups showed dose-dependent and
statistically significant improvement in the primary endpoint (percent change in EASI from
Baseline at Week 16)
• LEB demonstrated a dose-dependent response across all endpoints measured, with marked
improvement at both 250 mg Q2W and Q4W doses; for skin symptoms, an effect was seen
at Week 4
• Effects on itch were observed as early as Day 2 in patients who received a 500 mg loading
dose at Day 0
• LEB was well tolerated, and consistent with previous studies, TEAE rates were low; across
all LEB AD studies,6 conjunctivitis has been reported at low rates similar to those in patients
receiving placebo
• These data highlight that selective blockade of IL-13 with LEB leads to improvements in key
AD clinical severity scores and pruritus while maintaining a favorable safety profile
REFERENCES
1. Bieber T. Ann Dermatol. 2010;22(2):125-37.
2. Drucker AM, Wang AR, Li WQ, et al. J Invest Dermatol. 2017;137(1):26-30.
3. Moyle M, Cevikbas F, Harden JL, Guttman-Yassky E. Exp Dermatol. 2019;28(7):756-68.
4. Bieber T. Allergy. 2019. [Epub ehead of print]
5. Tsoi LC, Rodriguez E, Degenhardt F, et al. J Invest Dermatol. 2019; 139(7):1480-89.
6. Simpson EL, Flohr C, Eichenfield LF, et al. J Am Acad Dermatol. 2018;78(5):863-71.
ACKNOWLEDGEMENTS
This study was funded by Dermira, Inc. Medical writing support was provided by Prescott Medical Communications Group (Chicago, IL). All costs associated with development of this poster were funded by Dermira, Inc.
AUTHOR DISCLOSURES
EGY: Employee of Mount Sinai and has received research funds (grants paid to the institution) from Abbvie, Almirall, Amgen, AnaptysBio, Asana Biosciences, Boerhinger-Ingelhiem, Celgene, Dermavant, DS Biopharma, Eli Lilly,
Glenmark, Galderma, Innovaderm, Janssen, Kiniska, Kyowa Kirin, Leo Pharma, Novan, Pfizer, Ralexar, Regeneron, Sienna Biopharma, UCB, and Union Therapeutics. Consultant for EGY is also a consultant for Abbvie, Almirall,
Amgen, Asana Biosciences, Boerhinger-Ingelhiem, Cara Therapeutics, Celgene, Concert, DBV, Dermira, DS Biopharma, Eli Lilly, EMD Serono, Escalier, Galderma, Glenmark, Kyowa Kirin, Leo Pharma, Mitsubishi Tanabe, Pfizer,
RAPT Therapeutics, Regeneron, Sanofi, Sienna Biopharma, and Union Therapeutics. AB: Scientific adviser and/or clinical study investigator for AbbVie, Aclaris, Akros, Allergan, Almirall, Amgen, Arena, Athenex, Boehringer
Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly and Company, FLX Bio, Galderma, Genentech/Roche, GlaxoSmithKline, Janssen, Leo, Meiji, Merck Sharp & Dohme, Novartis, Pfizer, Purdue Pharma,
Regeneron, Revance, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB Pharma, Valeant, and Vidac. Paid speaker for AbbVie, Regeneron, and Sanofi Genzyme. LFE: Scientific adviser and/or clinical study
investigator for AbbVie, Allergan, Almirall, Amgen, Asana, Dermavant, Dermira, DS Biopharma, Eli Lilly, Forte, Galderma, Glenmark, Incyte, Leo, Matrisys, Novartis, Pfizer Ortho Dermatologics/Valeant, Regeneron, Sanofi Genzyme,
UCB Pharma. AP: Investigator for AbbVie, Anaptysbio, Eli Lilly, Galderma, Incyte, Leo, Novartis, Sanofi and Regeneron. Consultant for AbbVie, Asana, Dermavant, Dermira, Galderma, Eli Lilly, Forte, Leo, Menlo, Novartis, Pfizer,
Regeneron, and Sanofi. AA: Research, investigator, and/or consultant for AbbVie, Bristol-Myers Squibb, Dermavant, Dermira, Janssen, KHK, Leo, Lilly, Novartis, Ortho Dermatologics, Regeneron, Sanofi, and UCB. JD, RG: Employee
of Dermira. ES: Reports personal fees from AbbVie, Anacor, Boehringer-Ingelheim, Dermavant, Eli Lilly, Forte Bio, Incyte, Leo Pharmaceutical, MedImmune, Menlo Therapeutics, Pfizer, Pierre Fabre Dermo Cosmetique, Regeneron,
Roivant, Sanofi, and Valeant. Reports grants from AbbVie, Amgen, Celgene, Chugai, Eli Lilly, Galderma, Genentech, Kyowa Hakko Kirin, Leo Pharmaceuticals, MedImmune, Merck, Novartis, Pfizer, Regeneron, Sanofi, Tioga, and
Vanda.