Evidence map›Paper›PMID 29920993›Full record

ArticleCPT: pharmacometrics & systems pharmacology2018

Quantitative Systems Pharmacology Modeling of Acid Sphingomyelinase Deficiency and the Enzyme Replacement Therapy Olipudase Alfa Is an Innovative Tool for Linking Pathophysiology and Pharmacology.

Chanchala D Kaddi, Bradley Niesner, Rena Baek, Paul Jasper, John Pappas, John Tolsma, Jing Li, Zachary van Rijn, Mengdi Tao, Catherine Ortemann-Renon and 6 more

Abstract read
In one paragraph

Article in CPT: pharmacometrics & systems pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed.

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  19. Industrialization of Quantitative Systems Pharmacology.CPT: pharmacometrics & systems pharmacology · 2019
    Article
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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

16 authors.

Chanchala D KaddiTranslational Informatics, TMED, Sanofi, Bridgewater, New Jersey, USA.
Bradley NiesnerTranslational Informatics, TMED, Sanofi, Bridgewater, New Jersey, USA.
Rena BaekSanofi Genzyme, Cambridge, Massachusetts, USA.
Paul JasperRES Group Inc., Needham, Massachusetts, USA.
John PappasRES Group Inc., Needham, Massachusetts, USA.
John TolsmaRES Group Inc., Needham, Massachusetts, USA.
Jing LiTranslational Informatics, TMED, Sanofi, Bridgewater, New Jersey, USA.
Zachary van RijnTranslational Informatics, TMED, Sanofi, Bridgewater, New Jersey, USA.
Mengdi TaoTranslational Informatics, TMED, Sanofi, Bridgewater, New Jersey, USA.
Catherine Ortemann-RenonTranslational Informatics, TMED, Sanofi, Bridgewater, New Jersey, USA.
Rachael EastonTranslational Informatics, TMED, Sanofi, Bridgewater, New Jersey, USA.
Sharon TanSanofi Genzyme, Cambridge, Massachusetts, USA.
Ana Cristina PugaSanofi Genzyme, Cambridge, Massachusetts, USA.
Edward H SchuchmanGenetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Jeffrey S BarrettTranslational Informatics, TMED, Sanofi, Bridgewater, New Jersey, USA.
Karim AzerTranslational Informatics, TMED, Sanofi, Bridgewater, New Jersey, USA.

Funding

Acid Sphingomyelinase and Niemann-Pick DiseaseR37HD028607 · NICHD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SCHUCHMAN, EDWARD H. · 2012 to 2021
$4.2M
NICHD NIH HHS R37 HD028607
6 · The paper itself

Abstract

Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder with heterogeneous clinical manifestations, including hepatosplenomegaly and infiltrative pulmonary disease, and is associated with significant morbidity and mortality. Olipudase alfa (recombinant human acid sphingomyelinase) is an enzyme replacement therapy under development for the non-neurological manifestations of ASMD. We present a quantitative systems pharmacology (QSP) model supporting the clinical development of olipudase alfa. The model is multiscale and mechanistic, linking the enzymatic deficiency driving the disease to molecular-level, cellular-level, and organ-level effects. Model development was informed by natural history, and preclinical and clinical studies. By considering patient-specific pharmacokinetic (PK) profiles and indicators of disease severity, the model describes pharmacodynamic (PD) and clinical end points for individual patients. The ASMD QSP model provides a platform for quantitatively assessing systemic pharmacological effects in adult and pediatric patients, and explaining variability within and across these patient populations, thereby supporting the extrapolation of treatment response from adults to pediatrics.

Indexed as

Models, BiologicalAnimalsCalibrationEnzyme Replacement TherapyHumansMiceMice, KnockoutNiemann-Pick DiseasesRecombinant ProteinsSphingomyelin Phosphodiesteraseolipudase alfaRecombinant ProteinsSMPD1 protein, humanSphingomyelin Phosphodiesterase

Identifiers

PMID29920993
PMCPMC6063739

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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 Socratic graph.