S3200 ABP 710, a Biosimilar to Infliximab Reference Product: Supporting Extrapolation of Indications With a Focus on Crohn’s Disease
Notice bibliographique
Résumé
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
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».