A randomized, double-blind, multicenter study to compare the efficacy, safety, and immunogenicity of a proposed  
adalimumab biosimilar (GP2017) with originator adalimumab in patients with moderate-to-severe chronic plaque psoriasis

Andrew Blauvelt,1 Joseph F Fowler Jr,2 Ellen Schuck,3 Julia Jauch,3 Heike Woehling,3 and Craig L Leonardi4
1Oregon Medical Research Center, Portland, Oregon; 2Dermatology Specialists, Louisville, Kentucky; 3Hexal AG, Holzkirchen, Germany; 4Central Dermatology, St Louis, Missouri

Introduction
• GP2017 is being developed as a proposed biosimilar to originator 

adalimumab.
 – Extensive state-of-the-art analytical studies have shown that GP2017 
and originator adalimumab have identical amino acid sequences, 
indistinguishable secondary and tertiary structures, the same level of 
post-translational modifications, and similar in vitro functionality.1

 – Pharmacokinetic (PK) bioequivalence was demonstrated in phase I  
PK studies in healthy volunteers, with GP2017 and originator 
adalimumab having similar clinical safety and immunogenicity profiles.

• The purpose of this phase III confirmatory study (NCT02016105) was 
to show equivalent efficacy and comparable safety and immunogenicity 
between GP2017 and originator adalimumab up to 51 weeks in 
patients with moderate-to-severe chronic plaque psoriasis.
 – Here, data from randomization to Week 17 are presented for patients 
receiving GP2017 or originator adalimumab.

Study design
• This was a multicenter, randomized, double-blinded, comparator-controlled 

phase III confirmatory study with four study periods (Figure 1).

GP2017

GP2017

GP2017 GP2017

GP2017
Originator

adalimumab 
Originator

adalimumab 

Day 1
Randomization

Screening Treatment period 1 Treatment period 2 Extension period

End of study 

Week 16
Analysis of primary endpoint

Week 17
Re-randomization

Week 23 Week 29 Week 35

Sw
itched groups
W

17
–

W
51

C
ontinued groups

Random
ization to W

51

Week 51

GP2017 GP2017

{

Originator
adalimumab 

Originator
adalimumab 

Originator
adalimumab 

Originator
adalimumab 

Originator
adalimumab 

Figure 1. Study design

• Adult male and female patients with active, but clinically stable, 
moderate-to-severe chronic plaque psoriasis were eligible for enrolment 
if they were ≥18 years of age; had a baseline PASI score of ≥12, an 
Investigators Global Assessment (IGA) score of ≥3, and a body surface 
area (BSA) affected by plaque psoriasis of ≥10%; had previously received 
phototherapy or systemic psoriasis therapy or were candidates for such 
therapies; had no history of active or latent Hepatitis B and/or C infections 
or tuberculosis, and had not received prior treatment with adalimumab.

• In treatment period 1, patients were randomized to receive an initial dose 
of 80 mg subcutaneous GP2017 or originator adalimumab sourced from 
either the EU or US, followed by 40 mg every other week, starting one 
week after the initial dose, up to Week 17. 

Primary endpoint
• Proportion of patients who achieved a 75% improvement in the psoriasis 

area and severity index score (PASI 75) at Week 16.
 – Therapeutic equivalence was confirmed if the 95% confidence interval 
(CI) for the difference in PASI 75 response rates between GP2017 and 
originator adalimumab for the per-protocol set (PPS) was contained within 
a margin range of ±18%.

Secondary endpoints
• Percentage change from baseline until Week 16 in the continuous PASI 

score, with equivalence concluded if the 95% CI was within ±15%
• PASI 50, PASI 90 and PASI 100 response rates over time
• Percentage change from baseline in PASI score at each visit
• IGA response rate: proportion of patients with a score of 0 (clear) or 1 (almost 

clear) on the IGA scale (0–4) and ≥2 point improvement from baseline  
• Health-related quality of life (HRQoL) with regard to relative changes in  

the dermatology life quality index (DLQI) and EuroQol 5-dimension health 
(EQ-5D) status questionnaire from baseline to Weeks 11, 16, and 17

• Safety, immunogenicity, tolerability and local tolerance

Results 
Patients
• The full analysis set (FAS) comprised 231 patients who received GP2017 

and 234 patients who received originator adalimumab.
 – Of these, 197 and 196 patients completed the study up to Week 16 
with no major protocol deviations and were included in the PPS.

• Patient demographics and disease characteristics were balanced across 
both treatment groups (Table 1).

Table 1. Baseline patient and disease characteristics (FAS)

GP2017
(n=231)

Originator  
adalimumab 

(n=234)
Age (years), mean (SD) 45.6 (14.2) 46.9 (14.1)

Male, n (%) 142 (61.5) 142 (60.7)

Race, n (%)

Caucasian 196 (84.8) 201 (85.9)

Black 14 (6.1) 9 (3.8)

Asian 3 (1.3) 5 (2.1)

Other 18 (7.8) 19 (8.1)

BMI (kg/m2), mean (SD) 31.4 (8.1) 30.7 (7.5)

Duration since diagnosis (years), 
mean (SD) 15.3 (12.6) 16.9 (14.7)

PASI score, mean (SD) 19.9 (8.6) 20.2 (7.7)

IGA score, n (%)

3=Moderate 152 (65.8) 154 (65.8)

4=Severe 79 (34.2) 80 (34.2)

% BSA affected, mean (SD) 28.9 (17.1) 29.7 (15.6)

Presence of psoriatic arthritis, n (%) 52 (22.5) 46 (19.7)

Prior systemic psoriasis therapy, n (%)

Biologic 54 (23.4) 44 (18.8)

Nonbiologic 72 (31.2) 81 (34.6)

BMI, body mass index; BSA, body surface area; IGA, Investigator’s Global Assessment; 
PASI, psoriasis area and severity index; SD, standard deviation

Efficacy
• In the PPS, the PASI 75 response rate difference at Week 16 was 1.8% 

(66.8% for GP2017 and 65.0% for originator adalimumab).
 – As the 95% CI was contained within the prespecified margin range of 
±18%, equivalent efficacy between GP2017 and originator adalimumab 
was confirmed (Figure 2A).

• Using a mixed model repeated measures method, mean percent change 
(improvement) from baseline up to Week 16 in PASI score was 60.7% for 
GP2017 and 61.5% with originator adalimumab in the PPS.
 – The 95% CI for the difference in the percentage change from baseline 
in PASI up to Week 16 was contained within ±15%; thereby showing 
therapeutic equivalence (Figure 2B).

Pa
tie

nt
s 

w
ith

 P
A

SI
 7

5
re

sp
on

se
 a

t W
ee

k 
16

, %

M
ea

n 
pe

rc
en

t c
ha

ng
e 

in
 P

A
SI

fro
m

 b
as

el
in

e 
to

 W
ee

k 
16

1.8%
(95% CI:

–7.46% to 11.15%)

A B

–0.8%
(95% CI:

–3.15% to 4.84%)

100

90

80

70

60

50

40

30

20

10

0
GP2017 Originator

adalimumab

GP2017
Originator

adalimumab

66.8 65

0

–10

–20

–30

–40

–50

–60

–70

–80

–90

–100

–60.7 –61.5

Figure 2. Primary and key secondary efficacy analyses (PPS)

• PASI response rates for GP2017 and originator adalimumab were similar 
over time (Figure 3).

%
 R

es
po

ns
de

rs

Week

PASI 50
GP2017 (n=197)
Originator adalimumab (n=196)

PASI 75

PASI 90

PASI 100

100

90

80

70

60

50

40

30

20

10

0
1 3 5 7 9 11 13 15 16 17

Figure 3. PASI response rates over time (PPS) 

• Mean percent changes in PASI score from baseline were similar (Figure 4)

%
 C

ha
ng

e 
fro

m
 b

as
el

in
e 

in
 P

A
SI

 s
co

re

Week

GP2017 (n=197)
Originator adalimumab (n=196)

10
0

–10
–20
–30
–40
–50
–60
–70
–80
–90

–100

1Baseline 3 5 7 9 11 13 15 16 17

Figure 4. Mean percent change from baseline in PASI score (PPS) 

• IGA response rates increased over time and were similar in both treatment 
groups (Figure 5).

%
 R

es
po

nd
er

s

Week

GP2017 (n=197)
Originator adalimumab (n=196)

70
60
50
40
30
20
10

0

1 3 5 7 9 11 13 15 16 17

Figure 5. IGA response rates over time (PPS) 

 
HRQoL
• The proportion of patients in the PPS reporting a DLQI of 0 or 1 (no effect 

at all on patient’s life) was similar between the treatment groups at all time 
points (Table 2). 

• Mean EQ visual analog scale scores, which range from 0 to 100 with lower 
scores indicating greater impairment in HRQoL, were also similar (Table 2). 

Table 2. Improvements in HRQoL (PPS)

DLQI score of 0 or 1, n/n (%) EQ visual analog scale score (SD)

GP2017
Originator 

adalimumab
GP2017

Originator  
adalimumab

Baseline 4/197 (2.0) 8/195 (4.1) 69.9 (22.1) 70.0 (23.2)

Week 11 79/194 (40.7) 79/193 (40.9) 77.5 (18.8) 78.2 (20.1)

Week 16 98/191 (51.3) 88/191 (46.1) 80.6 (17.0) 80.2 (20.0)

Week 17 97/192 (50.5) 93/192 (48.4) 80.5 (17.1) 80.7 (19.7)

Safety
• Among all patients who received ≥1 dose of study drug (safety analysis 

set; SAF), adverse events (AEs) occurred in 50.2% and 52.6% of patients 
treated with GP2017 and originator adalimumab, respectively; most of 
which were mild or moderate in severity (Table 3).

• The proportions of patients with severe AEs, serious AEs (SAEs), treatment-
related SAEs, AEs of special interest, AEs requiring study drug interruption, 
and discontinuations due to AEs were low across both treatment groups.

Table 3. Incidence of AEs from randomization to Week 17 (SAF)

Patients, n (%)
GP2017  
(n=231)

Originator adalimumab 
(n=234)

≥1 AE 116 (50.2) 123 (52.6)

≥1 severe AE 3 (1.3) 10 (4.3)

≥1 SAE 3 (1.3) 10 (4.3)

≥1 treatment-related AE 33 (14.3) 28 (12.0)

≥1 treatment-related SAE 1 (0.4) 3 (1.3)

AE of special interest 13 (5.6) 17 (7.3)

Treatment interruption due to AE 5 (2.2) 4 (1.7)

Discontinuation due to AE 4 (1.7) 7 (3.0)

Died 0 (0.0) 0 (0.0)

• Infections/infestations were most common, with nasopharyngitis most 
frequently reported (Table 4).

Table 4. AEs by system organ class and preferred term (≥2% in any treatment 
group) from randomization to Week 17 (SAF)

System organ class
    Preferred term
Patients, n (%)

GP2017 
(n=231)

Originator  
adalimumab 

(n=234)

Infections and infestations 55 (23.8) 56 (23.9)

Nasopharyngitis 13 (5.6) 15 (6.4)

Upper respiratory tract infection 11 (4.8) 9 (3.8)

Sinusitis 8 (3.5) 7 (3.0)

General disorders and administration site conditions 23 (10.0) 15 (6.4)

Injection site erythema 9 (3.9) 3 (1.3)

Fatigue 5 (2.2) 6 (2.6)

Musculoskeletal and connective tissue disorders 22 (9.5) 15 (6.4)

Back pain 6 (2.6) 3 (1.3)

Arthralgia 6 (2.6) 2 (0.9)

Nervous system disorders 19 (8.2) 14 (6.0)

Headache 11 (4.8) 8 (3.4)

Respiratory, thoracic and mediastinal disorders 15 (6.5) 15 (6.4)

Gastrointestinal disorders 14 (6.1) 27 (11.5)

Diarrhea 2 (0.9) 9 (3.8)

Skin and subcutaneous tissue disorders 12 (5.2) 15 (6.4)

Injury, poisoning and procedural complications 9 (3.9) 8 (3.4)

Investigations 8 (3.5) 9 (3.8)

Psychiatric disorders 6 (2.6) 5 (2.1)

Metabolism and nutrition disorders 5 (2.2) 7 (3.0)

Neoplasms benign, malignant and unspecified 4 (1.7) 5 (2.1)

Blood and lymphatic system disorders 3 (1.3) 5 (2.1)

Vascular disorders 2 (0.9) 7 (3.0)

Reproductive system and breast disorders 2 (0.9) 5 (2.1)

Immunogenicity
• 36.8% patients treated with GP2017 and 34.1% of patients treated with 

originator adalimumab were anti-drug antibody (ADA)-positive at least once 
up to Week 17.

• Approximately 80% of ADA were neutralizing. 

Conclusions
• Week 17 results of this phase III confirmatory study show 

equivalent efficacy of GP2017 and originator adalimumab.

• Safety and immunogenicity profiles of GP2017 and 
originator adalimumab were also similar and consistent  
with clinical experience with originator adalimumab.

Reference
1. Schiestl M, Roesli C. Am J Gastroenterol 2016; 111:S260–S335

Disclosure Statement
NCT02016105 is sponsored by Sandoz. ES, JJ, and HW are paid employees of 
Hexal AG. CL has served as a consultant for Abbvie, Amgen, Boehringer Ingelheim, 
Dermira, Janssen, Eli-Lilly, Leo, Sandoz, UCB, Pfizer and Vitae and is a member of the 
Speaker bureau for Abbvie, Celgene, Novartis and Eli Lilly. Medical writing support 
was provided by Spirit Medical Communications, funded by Sandoz.


	FC17PosterSandozBlauvelt.pdf