Phase I studies of infliximab and rituximab biosimilars demonstrate pharmacokinetic similarity

The phase I double-blind studies were designed to demonstrate the pharmacokinetic similarity of Pfizer’s biosimilar infliximab (PF-06438179) and biosimilar rituximab (PF-05280586) to Remicade (infliximab) and MabThera/Rituxan (rituximab), respectively, sourced from the US and EU, and between the US- and EU-sourced products. Safety was also evaluated.

For the infliximab trial, 151 healthy volunteers were enrolled and randomized 1:1:1 to the three treatment arms and 146 received a single 10 mg intravenous dose of PF-06438179 (n = 49), infliximab-US (n = 48) or infliximab-EU (n = 49).

For the rituximab trial, 220 subjects with active rheumatoid arthritis on a background of methotrexate who had an inadequate response to one or more tumour necrosis factor (TNF)-antagonist therapies were randomized 1:1:1 and received 1,000 mg intravenous doses of PF-05280586, rituximab-US or rituximab-EU on Days 1 and 15 (with stable background regimen of methotrexate).

For both trials the three study drugs exhibited a similar pharmacokinetic profile, which is characterized by a rapid increase of serum drug concentration during infusion followed by a multi-phasic decline in drug concentrations. In both studies, the 90% confidence interval for the ratios of C_max, AUC_t, and AUC_0-∞were within the bioequivalence acceptance window of 80–125% for the comparisons of PF-06438179 to infliximab-US or infliximab-EU, and infliximab-EU to infliximab-US and for the comparisons of PF-05280586 to rituximab-US and rituximab-EU, and rituximab-EU to rituximab-US. The safety profile was also similar across all three drugs in both trials.

The authors therefore concluded that the studies demonstrated the pharmacokinetic similarity of PF-06438179 to infliximab and of PF-05280586 to rituximab. The three study drugs in both trials were also generally safe and well-tolerated.

Conflict of interest
All of the authors of the abstracts [1, 2] are employees of Pfizer.

Editor’s comment
It should be noted that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

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References
1. Udata C, et al. A phase I pharmacokinetics trial comparing PF-06438179 (a potential biosimilar) and infliximab in healthy volunteers (REFLECTIONS B537-01). EULAR 2014, Paris, France; 11-14 June 2014.
2. Yin D, et al. A phase I pharmacokinetics trial comparing PF-05280586 (a potential biosimilar) and rituximab in subjects with active rheumatoid arthritis with active disease in TNF failures (REFLECTIONS B328-01). EULAR 2014, Paris, France; 11-14 June 2014.

Source: www.gabionline.net