FDA Approves Amgen's Infliximab Biosimilar, Avsola

The FDA has approved Amgen’s infliximab biosimilar, Avsola (infliximab-axxq), referencing Remicade. The biosimilar was approved to treat Crohn disease (CD), pediatric CD, ulcerative colitis (UC), pediatric UC, rheumatoid arthritis (RA), ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.

The biosimilar was studied in a phase 3 clinical trial in patients with RA.

In the multicenter, randomized, double-blind, active-controlled, multiple-dose study, 556 patients were treated with the biosimilar (n = 278) or the reference (n = 278) at a dose of 3 mg/kg on day 1 and at weeks 2 and 6, then every 8 weeks until week 22. The primary end point of the study was response difference in terms of the ACR criteria for 20% improvement (ACR20) at week 22.

Patients who completed the 22 weeks who were initially given the reference drug were randomized to continue treatment with the reference (n = 121) or switch to the biosimilar (n = 119) and receive treatment until week 46; patients randomized to the biosimilar continued their therapy (n = 244) until week 46.

The response difference in terms of ACR20 at week 22 was 9.37 (90% CI, 2.67-15.96), and, write the authors, results of the ACR20, ACR50, and ACR70 response rates across groups were similar, with overlapping 95% CIs of ACR response rates between groups at all and with narrow response differences at all time points.

Additionally, a phase 1 clinical trial, reported this October, demonstrated the pharmacokinetic (PK) similarity between the biosimilar and its US and EU references.²

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 (ABP 710), 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.

FDA approval of the biosimilar comes not long after the drug maker withdrew its application for the biosimilar from the European Medicines Agency. Amgen said in a letter to the regulator that its withdrawal was due to a change in product strategy.

Avsola joins 3 other FDA-approved infliximab biosimilars in the United States: Inflectra, Renflexis, and Ixifi. Only Inflectra and Renflexis are commercially available in the United States; Pfizer, developer of Ixifi, said when its product was approved that it had no plans to launch Ixifi in the United States, but would continue to focus its efforts on Inflectra.

No launch date for Avsola has been announced.

References

1. Genovese M, Sanchez-Burson J, Balázs É, Everding A, Oh MS, Fanjiang G, Cohen S. Efficacy of biosimilar candidate ABP 710 in a phase 3 study in subjects with moderate to severe RA: additional analysis focusing on the ACR individual components. Presented at: The American College of Rheumatology Annual Meeting, November 8-13, 2019; Atlanta, Georgia. Abstract 519.

2. 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.