Assessing Functional Similarity of Biosimilar ABP 654 and Ustekinumab in Samples from Patients with Crohn’s Disease
Bibliographic record
Abstract
Ian N Foltz,1 Kevin Gaida,2 Helen Y Wong,1 Michael Ng,1 Marijana Busch,1 Jennifer L Liu3 1Amgen Research, Department of Therapeutic Discovery, Amgen Inc., Burnaby, BC, V5A1V7, Canada; 2Research and Development, Amgen Inc., Thousand Oaks, CA, 91320, USA; 3Biosimilar Process Development, Amgen Inc., Thousand Oaks, CA, 91320, USACorrespondence: Jennifer L Liu, Biosimilar Process Development, Amgen, Inc., One Amgen Center Dr, Thousand Oaks, CA, 91320, USA, Tel +1-805-447-2246, Email jliu@amgen.comPurpose: ABP 654 is the first FDA-approved interchangeable biosimilar for ustekinumab reference product (RP). To support the totality of evidence (TOE), in vitro pharmacology studies were conducted in peripheral blood mononuclear cells (PBMCs) from healthy human donors and Crohnâs disease (CD) patients to evaluate IL-23 and IL-12 inhibition by ABP 654 and ustekinumab RP relevant to the mechanism of action of chronic inflammation.Methods: ABP 654 and ustekinumab RP were assessed using inhibition of IL-23 and IL-12-mediated IFN-γ release, signal transducer and activator of transcription (STAT)3 and STAT4 phosphorylation, and IL-17 release. IFN-γ levels were determined using homogenous time-resolved fluorescence (HTRF). STAT3 and STAT4 phosphorylation were measured by flow cytometry. IL-17 was measured using a Cisbio IL-17 detection kit. IC50 values were calculated to assess the relative potency of ABP 654 and ustekinumab RP.Results: ABP 654 and ustekinumab RP demonstrated similar inhibition and relative potency of IL-23 and IL-12-mediated IFN-γ release, and no difference in inhibition of IL-23/IL-12-mediated STAT3/STAT4 phosphorylation in healthy donor PBMCs, as evidenced by the overlapping standard deviation (SD). In CD PBMCs, ABP 654 and ustekinumab RP also showed no difference in IC50 values for inhibition of IL-23/IL-12-mediated STAT3/STAT4 phosphorylation. ABP 654 and ustekinumab RP showed no difference in IC50 values for IL-23-induced IL-17 release, in either healthy (ABP 654, 458.7± 110.8 pM; ustekinumab (EU), 514.6± 48.7 pM) or CD (ABP 654, 260.8± 88.5 pM; ustekinumab (EU), 256.9± 96.8 pM) donor cells with overlapping SD.Conclusion: These studies demonstrated similar inhibition of IL-23 and IL-12 function by ABP 654 and ustekinumab RP in both healthy and CD PBMCs. Overall, these assays support the conclusion that ABP 654 and ustekinumab RP are functionally similar, thereby contributing to the TOE supporting a demonstration of biosimilarity.Keywords: ABP 654, biosimilar pharmaceuticals, Crohnâs disease, interleukin-12, interleukin-23, interchangeable
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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".