Development of a proposed biosimilar product based on the demonstration of physicochemical, pharmacologic and clinical similarity to pegfilgrastim.
Bibliographic record
Abstract
e13534 Background: Biosimilar development involves extensive analytical characterization to ensure similarity to the reference medicinal product to support the demonstration of similarity in terms of clinical efficacy and safety. We report the comparative physicochemical, functional and clinical characterization of the proposed biosimilar, Pegylated Apo-Filgrastim (Pelgraz), to the reference product Neulasta. Methods: A variety of orthogonal physicochemical methods were applied to analyze primary and higher order structures, purity, and biological activity. Methods included spectroscopic and chromatographic methods, and a cell based potency assay. A phase I study in 66 healthy volunteers assessed the PK/PD similarity of Pelgraz and Neulasta following single-dose administration of 6 mg. A Phase III efficacy and safety study in ~600 breast cancer patients receiving TAC chemotherapy in adjuvant setting assessed and compared Pelgraz to US and EU Neulasta. Both studies included immunogenicity assessment. Results: Pelgraz has the same primary and higher order structure as Neulasta, demonstrated by peptide mapping and hydrogen-deuterium exchange. As determined by SE-HPLC, purity of Pelgraz batches averaged 99.4% vs. 97.8% for Neulasta. Pelgraz was shown to be equivalent to Neulasta in cell based bioassays. Results from the phase I study demonstrated the PK and PD similarity of these products with the 90% Confidence Interval (CI) for primary PK endpoints (AUC and Cmax)and 95% CI for primary PD endpoints (AUEC and Emax of the absolute neutrophil count) lying within pre-defined acceptance margins of 80-125%. The phase III study demonstrated similarity of efficacy for Pelgraz and Neulasta as assessed by the primary efficacy endpoint Duration of Severe Neutropenia (DSN), with the 95% CI of the difference in mean DSN falling within the pre-defined equivalence margin of ± 0.5 days. The safety and immunogenicity profile of Pelgraz was similar to that of Neulasta. Conclusions: In vitro analyses demonstrate finger-print-like similarity, and the clinical program demonstrated that there are no clinically meaningful differences between Pelgraz and Neulasta.
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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 | 0.012 | 0.009 |
| 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 | 0.001 | 0.001 |
| 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".