Pharmacokinetics of a proposed tocilizumab biosimilar (MSB11456) versus US-licensed tocilizumab: results of a randomized, double-blind, single-intravenous dose study in healthy adults

Figures & data

Figure 1. Subject disposition.

AE, Adverse events; PK, Pharmacokinetics.

Table 1. Subject demographics and characteristics at baseline by treatment groups. Safety analysis set.

Category or Statistic	MSB11456 (N = 62)	US-licensed tocilizumab (N = 66)
Female, n (%) Male, n (%)	21 (33.9) 41 (66.1)	19 (28.8) 47 (71.2)
Race, n (%) White	62 (100)	66 (100)
Ethnicity, n (%) Not Hispanic or Latino	62 (100)	66 (100)
Age (years), mean ± SD	35.5 ± 9.5	32.8 ± 9
Baseline body weight (kg), mean ± SD	77.10 ± 9.3	76.53 ± 10.1
Baseline BMI (kg/m^2), mean ± SD	25.15 ± 2.7	25.14 ± 2.8
Subjects with ≥1 medical history^a, n (%)	33 (53.2)	32 (48.5)

^aNo medical history was considered to be of clinical significance.

BMI, body mass index; n, number of subjects, SD, standard deviation.

Figure 2. Arithmetic mean (±SD) tocilizumab serum concentrations^a versus time on a linear scale following a one-hour 8 mg/kg IV infusion of MSB11456 and US-licensed tocilizumab in healthy subjects (pharmacokinetic analysis set).

Table 2. Summary of tocilizumab serum pharmacokinetic parameters following a one-hour 8 mg/kg IV infusion of MSB11456 and US-licensed tocilizumab in healthy subjects (pharmacokinetic analysis set).

PK Parameter (unit)	MSB11456 (N = 62)	US-licensed tocilizumab (N = 66)
Cmax (μg/mL) mean ± SD Geometric mean (%GeoCV)	176 ± 21.5 175 (12.2)	174 ± 28.4 172 (16.7)
AUC0–last (h·μg/mL) mean ± SD Geometric mean (%GeoCV)	29179 ± 4242 28858 (15.3)	28316 ± 4608 27926 (17.2)
AUC0–inf (h·μg/mL) mean ± SD Geometric mean (%GeoCV)	32343 ± 5185 31902 (17.2)	31449 ± 5655 30928 (18.9)
λz (/h) mean ± SD Geometric mean (%GeoCV)	0.00353 ± 0.000757 0.00346 (19.3)	0.00355 ± 0.000807 0.00347 (20.4)
t1/2 (h) mean ± SD Geometric mean (%GeoCV)	204 ± 35.1 200 (19.3)	203 ± 36.9 200 (20.4)
CL (mL/h) mean ± SD Geometric mean (%GeoCV)	19.5 ± 3.34 19.2 (16.7)	20.0 ± 3.91 19.6 (18.8)
tmax (h) Median Min, Max	2.00 0.78, 8.02	2.00 1.00, 12.00

%GeoCV, geometric coefficient of variation in percentage; AUC, area under the concentration–time curve; AUC_0–inf, AUC from time zero to infinity; AUC_0–last, AUC from time zero to the time of the last quantifiable concentration; CI, confidence interval; CL, total clearance; C_max, maximum observed serum concentration; λz, terminal elimination rate constant; PK, pharmacokinetics; t_max, time to maximum observed serum concentration; t_1/2, terminal elimination half-life.

Table 3. Statistical analysis of the bioequivalence of a one-hour 8 mg/kg IV infusion of MSB11456 to US-licensed tocilizumab in healthy subjects (pharmacokinetic analysis set); primary and secondary pharmacokinetic parameters.

	MSB11456 (N = 62)	US-licensed tocilizumab (N = 66)	Ratio MSB1456/US-licensed tocilizumab
PK Parameter (unit)	GLSM (95% CI)	GLSM (95% CI)	GLSM	(90% CI)
AUC0–last (h·μg/mL)	28,858 (27,704, 30,060)	27,926 (26,843, 29,053)	103.34	(98.53, 108.37)
Cmax (μg/mL)	175 (168, 181)	172 (166, 178)	101.48	(97.23, 105.92)
AUC0–inf (h·μg/mL)	31,902 (30,494, 33,376)	30,928 (29,603, 32,311)	103.15	(97.86, 108.73)

The analysis was performed on natural logarithm (ln) transformed parameters using an analysis of variance model with treatment as a fixed effect.

AUC, area under the concentration–time curve; AUC_0–last, AUC from time zero to the time of the last quantifiable concentration; AUC_0–inf, AUC from time zero to infinity; CI, confidence interval; C_max, maximum observed serum concentration; GLSM, geometric least squares mean; IV, intravenous; PK, pharmacokinetics.

Figure 3. Bar chart for overall ADA and NAb positivity rate following a one-hour 8 mg/kg IV infusion of MSB11456 and US-licensed tocilizumab in healthy subjects (safety analysis set).

Figure 4. ADA incidence over time.

Figure 5. The most common^a TEAEs^b by preferred term and severity of TEAEs overall following a one-hour 8 mg/kg IV infusion of MSB11456 and US-licensed tocilizumab in healthy subjects^c (safety analysis set).