GP2017-HCF, a high concentration formulation, demonstrates similar pharmacokinetics, immunogenicity and safety to GP2017, an approved adalimumab biosimilar

Figures & data

Table 1. Subject demographics (Safety set).

Characteristic	GP2017-HCF N = 162	GP2017 N = 168
Age (years), mean (SD)	36.8 (9.04)	37.8 (9.52)
Male, n (%)	162 (100)	168 (100)
Race, n (%)
American Indian or Alaska Native	0	1 (0.6)
Asian	1 (0.6)	1 (0.6)
Black or African American	38 (23.5)	26 (15.5)
Multiple	1 (0.6)	0
White	122 (75.3)	140 (83.3)
Ethnicity, n (%)
Hispanic or Latino	134 (82.7)	140 (83.3)
Not Hispanic or Latino	28 (17.3)	28 (16.7)
Height (cm), mean (SD)	173.7 (6.47)	174.4 (6.65)
Weight (kg), mean (SD)	81.21 (9.10)	81.24 (8.79)
Weight stratification factor, n (%)
65.0 – <76.0 kg	50 (30.9)	50 (29.8)
76.0 – <92.0 kg	94 (58.0)	100 (59.5)
92.0–110.0 kg	18 (11.1)	18 (10.7)
BMI (kg/m^2), mean (SD)	26.90 (2.24)	26.70 (2.34)

BMI, body mass index; SD, standard deviation

Figure 1. Mean (±SD) linear (a) and semilogarithmic (b) serum concentration-time profiles (Safety analysis set).

Figure 2. Forest plot of PK endpoints (PK analysis set).

Table 2. Comparison of the PK parameters of GP2017-HCF and GP2017 (PK analysis set).

PK parameter (unit)	Treatment	n	Geometric LS means	Ratio GP2017-HCF/ GP2017
				Point estimate	90% CI(Lower, Upper)
Cmax (ng/mL)	GP2017-HCF	152	3247	1.0242	(0.9536, 1.1001)
	GP2017	148	3170
AUC0-inf (h*ng/mL)	GP2017-HCF	143	2334410	1.0605	(0.9758, 1.1525)
	GP2017	142	2201267
AUC0-360 (h*ng/mL)	GP2017-HCF	152	904669	1.0318	(0.9568, 1.1127)
	GP2017	148	876775
AUC0-last (h*ng/mL)	GP2017-HCF	152	1859656	1.0432	(0.9404, 1.1572)
	GP2017	148	1782651

n = number of subjects by treatment group with evaluable PK parameter data. ANCOVA was performed for each PK parameter including treatment as a fixed effect and baseline body weight (at Day −1) as a covariate. ANCOVA, analysis of covariance; AUC, area under the concentration–time curve; C_max, maximum serum concentration; PK, pharmacokinetics

Table 3. PK comparability by ADA subpopulation (PK analysis set).

				Ratio GP2017-HCF/ GP2017
PK parameter (unit)	Treatment	n	Geometric LS means	Point estimate	90% CI(Lower, Upper)
ADA-positive
Cmax (ng/mL)	GP2017-HCF	106	3246	1.0505	(0.9597, 1.1499)
	GP2017	98	3090
AUC0-inf (h*ng/mL)	GP2017-HCF	98	2087731	1.1085	(1.0022, 1.2260)
	GP2017	92	1883389
AUC0-360 (h*ng/mL)	GP2017-HCF	106	896459	1.0751	(0.9761, 1.1841)
	GP2017	98	833858
AUC0-last (h*ng/mL)	GP2017-HCF	106	1625243	1.0918	(0.9574, 1.2451)
	GP2017	98	1488565
ADA-negative
Cmax (ng/mL)	GP2017-HCF	46	3252	0.9759	(0.8676, 1.0976)
	GP2017	50	3332
AUC0-inf (h*ng/mL)	GP2017-HCF	45	2970576	1.0108	(0.9097, 1.1232)
	GP2017	50	2938790
AUC0-360 (h*ng/mL)	GP2017-HCF	46	926803	0.9608	(0.8546, 1.0803)
	GP2017	50	964593
AUC0-last (h*ng/mL)	GP2017-HCF	46	2536196	0.9990	(0.8982, 1.1111)
	GP2017	50	2538700

n = number of subjects by treatment group with evaluable PK parameter data. ANCOVA was performed for each PK parameter including treatment as a fixed-effect and baseline body weight (at Day −1) as a covariate. ANCOVA, analysis of covariance; AUC, area under the concentration–time curve; C_max, maximum serum concentration; PK, pharmacokinetics

Table 4. Summary of immunogenicity results (Safety analysis set).

Visit	Result	GP2017-HCFN = 162 n (%)	GP2017N = 168 n (%)
Day 1 (Pre-dose)	ADA Positive	1 (0.6)	0
	NAb Positive	1 (0.6)	0
Day 3	ADA Positive	0	0
	NAb Positive	0	0
Day 7	ADA Positive	2 (1.2)	4 (2.4)
	NAb Positive	2 (1.2)	4 (2.4)
Day 10	ADA Positive	2 (1.2)	5 (3.0)
	NAb Positive	2 (1.2)	4 (2.4)
Day 16	ADA Positive	58 (35.8)	50 (29.8)
	NAb Positive	26 (16.0)	24 (14.3)
Day 23	ADA Positive	68 (42.0)	61 (36.3)
	NAb Positive	34 (21.0)	40 (23.8)
Day 30	ADA Positive	43 (26.5)	47 (28.0)
	NAb Positive	29 (17.9)	36 (21.4)
Day 44	ADA Positive	41 (25.3)	44 (26.2)
	NAb Positive	40 (24.7)	44 (26.2)
Day 58	ADA Positive	68 (42.0)	72 (42.9)
	NAb Positive	67 (41.4)	72 (42.9)
Day 72	ADA Positive	94 (58.0)	90 (53.6)
	NAb Positive	93 (57.4)	90 (53.6)
Overall (up to Day 72)	ADA Positive	112 (69.1)	109 (64.9)
	ADA Negative	49 (30.2)	59 (35.1)
	NAb Positive	102 (63.0)	103 (61.3)
	Transient	18 (11.1)	17 (10.1)

The number of subjects of each category at each visit (n) is displayed in the table. Percentage is calculated as 100*n/N. ‘Overall’ indicates a subject had an ADA negative test result at baseline and had at least 1 ADA positive result (ADA-positive) or consistently negative results (ADA-negative) post-baseline. ‘Transient’ indicates that a subject experienced a final negative ADA result at any visit following a positive ADA result.

ADA, anti-drug antibody; NAb, neutralizing antibody

Table 5. TEAEs by primary system organ class and preferred term (at least 2% of subjects in any treatment group) (Safety set).

Primary system organ class Preferred term	GP2017-HCFN = 162n (%)	GP2017N = 168n (%)
Number of subjects with at least 1 event	80 (49.4)	95 (56.5)
General disorders and administration site conditions	55 (34.0)	69 (41.1)
Injection site reaction	50 (30.9)	63 (37.5)
Investigations	16 (9.9)	24 (14.3)
Hemoglobin decreased	4 (2.5)	5 (3.0)
Alanine aminotransferase increased	5 (3.1)	3 (1.8)
Aspartate aminotransferase increased	4 (2.5)	4 (2.4)
Weight decreased	2 (1.2)	6 (3.6)
Musculoskeletal and connective tissue disorders	8 (4.9)	14 (8.3)
Back pain	3 (1.9)	4 (2.4)
Pain in extremity	1 (0.6)	6 (3.6)
Nervous system disorders	8 (4.9)	6 (3.6)
Headache	6 (3.7)	4 (2.4)
Skin and subcutaneous tissue disorders	10 (6.2)	4 (2.4)
Rash	4 (2.5)	1 (0.6)
Gastrointestinal disorders	8 (4.9)	3 (1.8)
Respiratory, thoracic and mediastinal disorders	2 (1.2)	6 (3.6)
Eye disorders	1 (0.6)	4 (2.4)
Injury, poisoning and procedural complications	4 (2.5)	1 (0.6)

TEAEs are events that started or worsened after study treatment. A subject with multiple occurrences of an event within the same primary system organ class or preferred term was counted only once. Primary SOCs and PTs are sorted in descending frequency (total column of source table). MedDRA version 24.1

PT, preferred term; SOC, system organ class; TEAEs, treatment-emergent adverse events

Figure 3. Box plot of VAS scores.