Evidence map›Paper›PMID 37735717›Full record

ReviewClinical and translational science2023

Dose selection for biological enzyme replacement therapy indicated for inborn errors of metabolism.

Yuen Yi Hon, Jie Wang, Henrietta Abodakpi, Anand Balakrishnan, Michael Pacanowski, Sushanta Chakder, Patroula Smpokou, Kathleen Donohue, Yow-Ming C Wang

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Clinical and translational science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
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

6 citing papers in PubMed, 11 citations in OpenAlex.

  1. 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

9 authors at 2 institutions in 1 country.

Yuen Yi HonDivision of Rare Diseases and Medical Genetics, Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, Office of New Drugs (OND), Center of Drug Evaluation and Research (CDER), Food and Drug Administration (FDA), Silver Spring, Maryland, USA.ORCID 0000-0002-6395-1087
Jie WangOffice of Clinical Pharmacology, Office of Translational Sciences, CDER, Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Henrietta AbodakpiOffice of Clinical Pharmacology, Office of Translational Sciences, CDER, Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Anand BalakrishnanOffice of Clinical Pharmacology, Office of Translational Sciences, CDER, Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Michael PacanowskiOffice of Clinical Pharmacology, Office of Translational Sciences, CDER, Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Sushanta ChakderDivision of Pharmacology and Toxicology, Office of Immunology and Inflammation, OND, CDER, Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Patroula SmpokouDivision of Rare Diseases and Medical Genetics, Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, Office of New Drugs (OND), Center of Drug Evaluation and Research (CDER), Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Kathleen DonohueDivision of Rare Diseases and Medical Genetics, Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, Office of New Drugs (OND), Center of Drug Evaluation and Research (CDER), Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Yow-Ming C WangOffice of Clinical Pharmacology, Office of Translational Sciences, CDER, Food and Drug Administration (FDA), Silver Spring, Maryland, USA.ORCID 0000-0002-0663-7358
United States Food and Drug Administration · USCenter for Drug Evaluation and Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This paper summarizes key features of the dose-finding strategies used in the development of 11 approved new molecular entities that are first-in-class enzyme replacement therapy (ERT), with a goal to gain insight into the dose exploration approaches to inform efficient dose-finding in future development of biological products for Inborn Errors of Metabolism (IEM). Dose exploration should preferably begin in in vitro studies, followed by testing multiple doses in an appropriate animal disease model, when available, which can provide important information for dose assessment in humans. Performing adequate dose-finding in early phase clinical studies in a well-defined study population, including pediatric subjects, is generally critical to inform dose selection for pivotal trials; alternatively, additional dose exploration can be incorporated as part of a pivotal trial. Two important considerations for successful dose selection include (1) identifying appropriate disease-specific endpoints, including pharmacodynamic (PD) end points and intermediate clinical end points or clinical end points, and (2) designing a study with adequate treatment durations for evaluating these end points. Appropriately selected PD biomarkers is useful for dose selection, and early development of these biomarkers can facilitate the overall clinical development program. Optimization of ERT doses, as well as evaluations of patient intrinsic factors and/or immune tolerance strategies may be necessary to overcome antibody responses or increase efficacy in IEM.

Indexed as

Enzyme Replacement TherapyAnimalsBiomarkersChildHumansBiomarkers

Identifiers

PMID37735717
PMCPMC10719471
OpenAlexW4386944427

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.