Evidence map›Paper›PMID 41319239›Full record

Trial reportClinical and translational science2025

Proteomic Identification of Plasma Biomarkers of Response to IL-5 Inhibitor Biologics in Healthy Subjects.

Lakshmi Manasa S Chekka, Deepti P Samarth, Kristina E Howard, Yan Guo, Esraa G Mohamed, Erica Decker, William Wheeler, Joel Wommack, Joseph Gogain, Jennifer Deering and 5 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical and translational science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Trial
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Lakshmi Manasa S ChekkaDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0001-5996-9180
Deepti P SamarthDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0001-6647-8558
Kristina E HowardDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0001-8891-754X
Yan GuoDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Esraa G MohamedDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Erica DeckerDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
William WheelerInformation Management Services, Inc, Rockville, Maryland, USA.
Joel WommackStandard BioTools, Inc., Boulder, Colorado, USA.
Joseph GogainStandard BioTools, Inc., Boulder, Colorado, USA.
Jennifer DeeringSpaulding Clinical Research, West Bend, Wisconsin, USA.
Sarah J SchrieberOffice of Therapeutic Biologics and Biosimilars, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Yow-Ming WangTherapeutic Biologics Program, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0002-0663-7358
David G StraussDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Jeffry FlorianDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0009-0000-1984-8026
Paula L HylandDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0000-0003-0516-3389

Funding

U.S. Food and Drug Administration
6 · The paper itself

Abstract

Proteomics can identify pharmacodynamic (PD) biomarkers by detecting protein changes in response to drug treatment, providing insights into drug mechanism and biological effects. In this study, we profiled over 7000 plasma proteins to identify potential PD biomarkers for the interleukin-5 (IL-5) inhibitors mepolizumab and reslizumab, which are approved for treating eosinophilic asthma. We used longitudinal plasma samples from healthy participants treated with a single dose of mepolizumab (n = 8, 24 mg) or reslizumab (n = 8, 0.8 mg/kg), or placebo (n = 8) to identify differentially expressed proteins. We then characterized PD biomarker candidates by their magnitude of response, area under the effect curve (AUEC), dose-response, variability, and replication of response at a lower dose for mepolizumab (n = 8, 12 mg) or reslizumab (n = 8, 0.4 mg/kg) compared to placebo. Eosinophil major basic protein (EMBP) and proteoglycan-3 (PRG3) were differentially expressed in response to mepolizumab and reslizumab, respectively, achieving Bonferroni-adjusted statistical significance (p-value < 6.86E-06) and nominal significance (p-value < 5.0E-05) with the other IL-5 inhibitor. EMBP showed a > 20% fold change difference with mepolizumab (24 mg) versus placebo at peak time, and PRG3 demonstrated a > 20% fold change with reslizumab (0.8 mg/kg) versus placebo at peak time. Both proteins had significant AUEC with both drug doses, with EMBP AUEC only significant (absolute AUEC high > low dose) at the higher mepolizumab dose. Both biomarkers showed dose-response trends and comparable variability to placebo. Our study identified EMBP and PRG3 as promising plasma PD biomarkers for IL-5 inhibitors, warranting further validation for early phase trials and biosimilar development programs.

Indexed as

Antibodies, Monoclonal, HumanizedInterleukin-5ProteomicsAdultBiomarkersDose-Response Relationship, DrugDouble-Blind MethodFemaleHealthy VolunteersHumansLongitudinal StudiesMaleMiddle AgedYoung AdultAntibodies, Monoclonal, HumanizedBiomarkersIL5 protein, humanInterleukin-5mepolizumabreslizumabbiomarkersinhibitorsinterleukin‐5pharmacodynamic biomarkersproteomics

Identifiers

PMID41319239
PMCPMC12665252

What OpenQuestion holds

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Registered trials

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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.