S3200 ABP 710, a Biosimilar to Infliximab Reference Product: Supporting Extrapolation of Indications With a Focus on Crohn’s Disease
Bibliographic record
Abstract
INTRODUCTION: ABP 710 (US: AVSOLA™ [infliximab-axxq]) is an approved biosimilar to infliximab reference product (RP). The primary mechanism of action (MOA) of infliximab RP is mediated by binding to soluble tumor necrosis factor (TNF) alpha, inhibiting its proinflammatory signaling. Secondary mechanisms mediated by binding to membrane bound (mb) TNF alpha may play a role in inflammatory disease as demonstrated by reverse signaling, mixed lymphocyte reactions (MLRs) and effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity. Here we examined specific ex-vivo functional studies to support extrapolation of ABP 710 to Crohn’s disease (CD). METHODS: Fecal calprotectin (FCal) levels were measured by ELISA and phenotyping of peripheral blood mononuclear cells (PBMCs) was carried out in healthy volunteers and in patients with CD by flow cytometry. ADCC was assessed in PBMCs isolated from 5 healthy volunteers and 3 patients with CD. Multiple lots of ABP 710 and RP sourced from the United States (US) and the European Union (EU) were compared for ADCC. RESULTS: FCal levels were higher in patients with CD as compared to control and were also higher in patients with CD with higher baseline levels of C-reactive protein (CRP). Peripheral blood immunophenotyping of patients with CD also demonstrated that most immune cell (granulocytes, lymphocytes, natural killer cells and monocytes) markers were similarly higher in patients with CD and with high CRP as compared to control (see Table). As with FCal, higher baseline CRP was associated with an increase in blood immune markers. ADCC data from PBMCs isolated from 5 healthy volunteers and 3 CD patients demonstrated similar function in ABP 710 as compared with the RP (US and EU) in all samples from healthy volunteers and in 2 out of 3 samples from patients with CD. CONCLUSION: ABP 710 infliximab RP biosimilar has previously been shown to be highly similar to the RP in efficacy, safety and immunogenicity. We have demonstrated that similarity extends to biological activity across key MOAs, including those mediated through mbTNF alpha which may be important for the efficacy of infliximab in patients with CD. Coupled with previously reported analytical similarity assessments, similar ex vivo ADCC activity in PBMCs isolated from healthy volunteers and patients with CD despite differences in physiological and blood phenotype indicators, contribute to the totality of evidence supporting efficacy of ABP 710 in CD.Table 1
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".