An article reviewed the totality of evidence leading to the approval of Amgen’s infliximab biosimilar ABP 710 (Avsola), which is currently approved in the US and Canada for all the indications of the originator (Remicade).
An article published in Advances in Therapyreviewed the totality of evidence leading to the approval of Amgen’s infliximab biosimilar ABP 710 (Avsola), which is currently approved in the US and Canada for all the indications of the originator.
The reference product (Remicade), a monoclonal antibody targeting tumor necrosis factor alpha (TNF- 𝝰), was the first biologic to demonstrate efficacy in rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis, and the first biologic approved to treat inflammatory bowel disease (IBD), the reviewers noted. ABP 710 is 1 of several infliximab biosimilars currently available, including CT-P13 (Remsima, Inflectra) and SB2 (Renflexis).
The totality of evidence required to support approval of a proposed biosimilar by the US FDA and European Medicines Agency includes evaluation of physicochemical attributes, non-clinical assessments of the mechanism(s) of action, a pharmacokinetic (PK) and pharmacodynamic (PD) study in healthy volunteers, and a comparative clinical study in a representative indication of the reference product (RP).
Structural and functional similarity
Analytical studies compared ABP 710 to reference infliximab sourced from both the US and EU. These studies demonstrated similarity in primary structure, including amino acid sequence and post-translational modifications, higher-order structure, particles and aggregates, and purity.
Minor differences in physicochemical attributes and post-translational modifications were observed in these studies. The authors explained that these differences were consistent with the different cell lines used to produce the RP and ABP 710, and “comprehensive biological characterization was used to verify that these mostly minor differences did not translate into functional differences.”
In vitro studies found ABP 710 had functional similarity to the infliximab originator in binding to soluble and membrane-bound TNF-𝝰, subsequent neutralization of TNF-𝝰’s proinflammatory biological activity, and effector functions.
The authors noted that these functions are relevant to multiple immune-mediated inflammatory disorders, and the results of the mechanisms of action studies “supported extrapolation to additional indications including IBD.”
Pharmacokinetics and pharmacodynamics
PK/PD studies in healthy volunteers are carried out, according to the authors, not only to demonstrate PK and PD similarity, “but also to understand the comparative safety and immunogenicity of the proposed biosimilar and its RP.”
A randomized, single-blind, single-dose study in healthy participants demonstrated similarity of ABP 710 to the originator sourced from the US and EU. Furthermore, safety and immunogenicity were comparable: according to the authors, similar incidences of treatment-related adverse events (AEs), binding anti-drug antibodies (ADAs), and neutralizing ADAs were reported in the three groups.
Clinical efficacy and safety
A comparative clinical trial in a representative indication of the RP is the final step in generating the totality of evidence to support the approval of a proposed biosimilar. For ABP 710, a comparative clinical trial demonstrated similarity in efficacy, safety, and immunogenicity to the RP in patients with rheumatoid arthritis (RA).
Patients with moderate-to-severe active RA and an inadequate response to methotrexate were enrolled in the 50-week study and were randomized to receive infusions of the biosimilar or the RP. At week 22, patients in the biosimilar group continued to receive ABP 710, and patients in the RP group were re-randomized to either continue the RP or switch to the biosimilar for the remainder of the study.
The primary endpoint of the study was the response difference in 20% improvement from baseline in the American College of Rheumatology core set of measurements at week 22 between the biosimilar and originator. The lower bound of the 90% confidence interval was within the predefined equivalence margin, whereas the upper bound exceeded the margin by 0.96%, meaning superiority could not be ruled out. However, the authors said, “post hoc analyses were consistent with both non-inferiority and non-superiority.”
Taking into account the primary endpoint and additional efficacy endpoints, the reviewers wrote, “overall results demonstrated that there were no clinically meaningful differences between ABP 710 and infliximab RP.”
Safety and immunogenicity outcomes were also similar between groups “and were not impacted by the single transition from infliximab RP to ABP 710.” Infections were the most common AEs, and AE incidence rates were similar in the 2 groups. Also, the results “were consistent with the known safety profile of infliximab with no new or unexpected safety signals.”
The authors concluded the totality of evidence “supported the conclusion that ABP 710 is highly similar to infliximab RP and supported scientific justification for extrapolation to all approved indications of infliximab RP, including IBD.” They added that use of infliximab biosimilars has grown since the approval of CT-P13 in 2016, and “ABP 710 offers another treatment alternative among infliximab biosimilars.”
Reinisch W, Cohen S, Ramchandani M, et al. A review of the totality of evidence for the development and approval of ABP 710 (Avsola), an infliximab biosimilar. Adv Ther. 2022;39(1):44-57. doi:10.1007/s12325-021-01944-y