Ahead of FDA Decision on ABP 710, Study Shows Biosimilar's PK Similarity to Reference Infliximab

In December 2018, biosimilar developer Amgen announced that it had submitted its proposed infliximab biosimilar, ABP 710, referencing Remicade, to the FDA for review. A regulatory decision is expected shortly, and last week, researchers published detailed results from the biosimilar’s phase 1 clinical study that evaluated the pharmacokinetic (PK) similarity of the biosimilar with its reference.

The randomized, single-blind, single-dose, 3-arm, parallel-group study was conducted among healthy volunteers at 2 centers in Australia. In total, 49 individuals were dosed, at 5 mg/kg, with the biosimilar, 50 with US-licensed reference infliximab, and 49 with EU-licensed reference infliximab. The primary end point was area under the serum concentration—time curve from time 0 extrapolated to infinity (AUC_inf).

The geometric mean ratio of AUC_inf was 0.89 between ABP 710 and the US-licensed reference, 1.00 between ABP 710 and the EU-licensed reference, and 1.11 between the US-licensed reference and the EU-licensed reference. The 90% CIs of the geometric mean ratios were fully contained within the prespecified PK equivalence margin of 0.80 to 1.25. Additionally, the 90% CIs for the ratio of least squares geometric means for peak serum concentration and AUC to the last measurable concentration were fully contained within the same margin, confirming PK similarity.

With respect to safety, 83.7% of the biosimilar group, 86.0% of the US-licensed reference group, and 83.7% of the EU-licensed reference group reported any treatment-emergent adverse event (AE), and there was 1 serious AE, which was reported in the EU-licensed reference group. The most commonly reported AEs were somnolence, headache, and nasopharyngitis.

Antidrug antibodies (ADAs) were developed by 39.6% of the biosimilar group, 32.0% of the US-licensed reference group, and 27.1% of the EU-licensed reference group though day 57. Neutralizing ADAs were detected in 12.5%, 10.0%, and 18.8% of the 3 groups, respectively. PK parameters were similarly affected by ADA binding status for all 3 treatment arms.

Results of the study, say the authors, demonstrate PK similarity among the 3 infliximabs, and the safety and immunogenicity profiles of the products were also similar.

Also part of the biosimilar’s clinical program was a phase 3 clinical trial in patients with rheumatoid arthritis. Amgen announced positive topline results from that trial in 2018. Notably, while the current phase 1 study provides a bridge between the EU- and US-licensed reference drugs—as is common among biosimilars for which sponsors seek both approval of the same biosimilar in both the European Union and United States—Amgen has announced that it no longer intends to pursue regulatory approval in the EU marketplace. In May of 2019, the drug maker withdrew its application from the European Medicines Agency, citing a change of product strategy.

Reference

Chow V, Oh M, Gesner MA, Fanjiang G. Pharmacokinetic similarity of ABP 710, a proposed biosimilar to infliximab: results from a randomized, single-blind, single-dose, parallel-group study in healthy subjects [published online October 19, 2019]. Clin Pharmacol Drug Dev. doi: 10.1002/cpdd.738.