2 New Studies Highlight Safety, Efficacy, PK of Subcutaneous CT-P13

Celltrion, maker of biosimilar infliximab CT-P13 (Remsima, Inflectra), has recently submitted an application to the European Medicines Agency for a subcutaneous formulation of the biosimilar.

Previous research has established that the proposed subcutaneous formulation of CT-P13 has similar safety and efficacy to the intravenous CT-P13 up to week 30 in patients with Crohn disease (CD) and rheumatoid arthritis. A new study sought to report the pharmacokinetics (PK), efficacy, and safety of the subcutaneous formulation in patients with CD up to 1 year of treatment.¹

The study enrolled 44 patients who were assigned to 1 of 4 cohorts. The first cohort received weight-based intravenous therapy, whereas the second, third, and fourth cohorts received fixed doses of 120 mg, 180 mg, and 240 mg, respectively, of the subcutaneous CT-P13 formulation every 2 weeks up to week 54.

Overall, clinical response results were comparable between the cohorts after randomization at week 6 and up to week 30. Clinical remission was numerically higher in the subcutaneous-therapy cohorts at week 54. The mean predose serum concentration of CT-P13 before next dose injection was higher in the subcutaneous-therapy cohorts than in the intravenous-therapy cohort throughout the study after randomization; these values increased with the dose of the subcutaneous product and were substantially higher than the target therapeutic concentration.

Safety profiles were comparable across cohorts, and, in total, 11.4% of patients reported injection-site reactions (ISRs), all of which were grade 1 or 2.

The researchers concluded that these results suggest similar efficacy and safety of intravenous and subcutaneous CT-P13 and that the novel formulation “may expand treatment options for use of infliximab biosimilar by providing high consistency in drug exposure during maintenance treatment.”

A second study of the biosimilar focused on evaluating the PK and overall safety of the subcutaneous formulation as administered by autoinjector versus prefilled syringe.²

A total of 218 healthy volunteers were randomized to receive a single 120-mg dose of the subcutaneous CT-P13 via autoinjector or prefilled syringe. At week 12, PK and safety were assessed.

Overall, the mean serum concentration of CT-P13 following a single dose showed a similar trend throughout the study period in both arms, and safety results were comparable between arms. The proportion of individuals who experienced ISRs was lower in the autoinjector group than in the prefilled syringe group, as was the mean of injection site pain.

The proportion of patients who developed antidrug antibodies was similar between arms.

According to the authors, these results demonstrate equivalent PK and comparable safety of the subcutaneous CT-P13 in healthy volunteers treated with either of the 2 administration options.

References

1. Reinisch W, Jang BI, Borzan V, et al. A novel formulation of CT-P13 (infliximab biosimilar) for subcutaneous administration: 1-year result from a phase 1 open-label randomised controlled trial in patients with active Crohn’s disease. Presented at the 14th Congress of the European Crohn’s and Colitis Organisation; March 6-9, 2019; Copenhagen, Denmark. Abstract DOP62. ecco-ibd.eu/publications/congress-abstract-s/abstracts-2019/item/dop62-a-novel-formulation-of-ct-p13-infliximab-biosimilar-for-subcutaneous-administration-1-year-result-from-a-phase-i-open-label-randomised-controlled-trial-in-patients-with-active-crohn-8217-s-disease.html.

2. Schreiber S, Ben-Horin S, Ye BD, et al. Development of a novel auto-injector of subcutaneous CT-P13 infliximab: phase 1 randomised, open-label, single-dose trial to compare the pharmacokinetics and safety to pre-filled syringe in healthy subjects. Presented at the 14th Congress of the European Crohn’s and Colitis Organisation; March 6-9, 2019; Copenhagen, Denmark. Abstract P679. ecco-ibd.eu/publications/congress-abstract-s/item/p679-development-of-a-novel-auto-injector-of-subcutaneous-ct-p13-infliximab-phase-i-randomised-open-label-single-dose-trial-to-compare-the-pharmacokinetics-and-safety-to-pre-filled-syringe-in-healthy-subjects.html.