ArticleClinical pharmacology and therapeutics2017
Refining Liver Safety Risk Assessment: Application of Mechanistic Modeling and Serum Biomarkers to Cimaglermin Alfa (GGF2) Clinical Trials.
Article in Clinical pharmacology and therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Safety, Tolerability, and Pharmacokinetics of Recombinant Human Neuregulin-1 in Healthy Chinese Subjects.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2023Trial
- Quantitative systems toxicology (QST) reproduces species differences in PF-04895162 liver safety due to combined mitochondrial and bile acid toxicity.Pharmacology research & perspectives · 2019Trial
- Quantitative systems toxicology: modelling to mechanistically understand and predict drug safety.Nature reviews. Drug discovery · 2026Review
- Quantitative Approaches to Accelerate MASH Drug Discovery and Development.Clinical pharmacology and therapeutics · 2025Review
- Review
- Establishing reference ranges for circulating biomarkers of drug-induced liver injury in healthy human volunteers.British journal of clinical pharmacology · 2025Article
- The Combination of a Human Biomimetic Liver Microphysiology System with BIOLOGXsym, a Quantitative Systems Toxicology (QST) Modeling Platform for Macromolecules, Provides Mechanistic Understanding of Tocilizumab- and GGF2-Induced Liver Injury.International journal of molecular sciences · 2023Article
- Applications of Quantitative Systems Pharmacology (QSP) in Drug Development for NAFLD and NASH and Its Regulatory Application.Pharmaceutical research · 2022Article
- [Research progress on laboratory diagnosis of drug-induced liver injury].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2020Article
- Assessing Effects of BHV-0223 40 mg Zydis Sublingual Formulation and Riluzole 50 mg Oral Tablet on Liver Function Test Parameters Utilizing DILIsym.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- The DILI-sim Initiative: Insights into Hepatotoxicity Mechanisms and Biomarker Interpretation.Clinical and translational science · 2019Review
- Drug-Induced Liver Injury: Biomarkers, Requirements, Candidates, and Validation.Frontiers in pharmacology · 2019Review
- Strategies for Early Prediction and Timely Recognition of Drug-Induced Liver Injury: The Case of Cyclin-Dependent Kinase 4/6 Inhibitors.Frontiers in pharmacology · 2019Review
- Mechanisms and biomarkers of liver regeneration after drug-induced liver injury.Advances in pharmacology (San Diego, Calif.) · 2019Review
- Improving Interpretation of New and Old Serum Biomarkers of Drug-Induced Liver Injury Through Mechanistic Modeling.CPT: pharmacometrics & systems pharmacology · 2018Article
- Systems Toxicology Approach to Identifying Paracetamol Overdose.CPT: pharmacometrics & systems pharmacology · 2018Article
- In silico modeling to optimize interpretation of liver safety biomarkers in clinical trials.Experimental biology and medicine (Maywood, N.J.) · 2018Review
- The transformation in biomarker detection and management of drug-induced liver injury.Liver international : official journal of the International Association for the Study of the Liver · 2017Review
- In Vitro Antioxidant Activities and the Therapeutic Potential of Some Newly Synthesized Chalcones Against 4-Acetaminophenol Induced Hepatotoxicity in Rats.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cimaglermin alfa (GGF2) is a recombinant human protein growth factor in development for heart failure. Phase I trials were suspended when two cimaglermin alfa-treated subjects experienced concomitant elevations in serum aminotransferases and total bilirubin, meeting current US Food and Drug Administration criteria for a serious liver safety signal (i.e., "Hy's Law"). We assayed mechanistic biomarkers in archived clinical trial serum samples which confirmed the hepatic origin of the aminotransferase elevations in these two subjects and identified apoptosis as the major mode of hepatocyte death. Using a mathematical model of drug-induced liver injury (DILIsym) and a simulated population, we estimated that the maximum hepatocyte loss in these two subjects was <13%, which would not result in liver dysfunction sufficient to significantly increase serum bilirubin levels. We conclude that the two subjects should not be considered Hy's Law cases and that mechanistic biomarkers and modeling can aid in refining liver safety risk assessment in clinical trials.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.