characteristics with those of the reference product. As these studies are specifically designed to assess pharmacokinetic endpoints these studies are typically conducted in healthy volunteers but may be conducted in participants depending upon a range of factors such as the potential risks associated with the use of the agent. During the current update period, four phase I pharmacokinetic studies comparing a potential biosimilar medicine with a reference product were reported. In each of the trials reported, the potential biosimilar met the pre-specified acceptance criteria for the relevant pharmacokinetic/pharmacodynamic parameter endpoints. A summary of the results of these studies are presented in the table below (Table 1). Table 1: Summary of phase I pharmacokinetic studies of potential biosimilar medicines Biosimilar Candidate Reference Product Design Population PK Outcomes (and PD where reported) Immunogenicity Outcomes Reference Adalimumab M923 (Momenta) Humira (US and EU) Randomised, double-blind, three-arm, study Healthy participants (n=324, randomised 1:1:1) 90%CI for the ratio between the geometric means of the from time zero extrapolated to infinite time (AUCinf), AUC from time 0 to 336hrs concentration (AUC336) and maximal plasma concentration (Cmax) were within the predefined bioequivalence interval of 0.80–1.25 At day 71 the proportion of confirmed ADA responses increased in all study groups to M923 = 78.0%, US Humira = 73.1%, and EU Humira = 75.7% The presence of IgE was confirmed in 13 subjects (2 in the M923 arm, 8 in the US Humira arm, and 3 in the EU Humira arm) [1] Biosimilar Candidate Reference Product Study Design Study Population PK Outcomes (and PD where reported) Immunogenicity Outcomes Reference Insulin lispro dose
SAR342434 (Sanofi) Humalog (Lilly) Randomised, 2 × two-arm crossover study Participants with type I diabetes with at least 6 months of continuous subcutaneous insulin infusion treatment 6/25 participants reported 14 infusion set occlusion events whilst receiving SAR342434 as compared to 4/27 participants reporting 9 events whilst receiving Humalog. The event rate of any hypoglycemia was similar with SAR342434 (7.15) Humalog (7.98) No hypersensitivity reactions or allergic reactions [2] Rituximab RTXM83 (mAbxience Research S.L) MabThera Population pharmacokinetic modelling of phase III clinical data Participants with large B-cell lymphoma (RTXM83=127, MabThera=214; serum concentrations: RTXM83=2703 MabThera=2638) 90%CI for the ratio between the geometric means of the from time zero extrapolated to infinite time (AUCinf) and maximal plasma concentration (Cmax) were within the predefined bioequivalence interval of 0.80–1.25 Median values for drug clearance were similar between antibody positive and negative subjects in both RTXM83 (10.8 vs 11.3 mL/ min, respectively) and MabThera groups (13.6 vs 11.3 mL/min, respectively) [3] Trastuzumab CT-P6 (Celltrion) Herceptin (US) Single-dose, randomised, double-blind, parallel group study Healthy adult male volunteers (n=70, randomised 1:1) 90% CI for the ratio of geometric least square means for area-under-the-curve from time zero extrapolated to infinite time (AUCinf), AUC from time 0 to last quantifiable concentration (AUClast) and maximal plasma concentration (Cmax) were within the prespecified limits of 80- 125% for the comparisons of CT-P6 with US Herceptin No participants were positive for anti-drug antibodies. [4] diffuse