Evidence map›Paper›PMID 38740427›Full record

ReviewJournal of inherited metabolic disease2024

Clinical pharmacology considerations for first-in-human clinical trials for enzyme replacement therapy.

Sydney Stern, Jie Wang, Ruo-Jing Li, Yuen Yi Hon, Shawna L Weis, Yow-Ming C Wang, Robert Schuck, Michael Pacanowski

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Journal of inherited metabolic disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

8 authors.

Sydney SternOffice of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Jie WangOffice of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.ORCID 0009-0003-0147-753X
Ruo-Jing LiOffice of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Yuen Yi HonOffice of Rare Disease, Pediatrics, Urologic and Reproductive Medicine, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Shawna L WeisOffice of Rare Disease, Pediatrics, Urologic and Reproductive Medicine, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Yow-Ming C WangOffice of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Robert SchuckOffice of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Michael PacanowskiOffice of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.

Funding

Intramural FDA HHS FD999999
6 · The paper itself

Abstract

Inborn errors of metabolism (IEM) such as lysosomal storage disorders (LSDs) are conditions caused by deficiency of one or more key enzymes, cofactors, or transporters involved in a specific metabolic pathway. Enzyme replacement therapy (ERT) provides an exogenous source of the affected enzyme and is one of the most effective treatment options for IEMs. In this paper, we review the first-in-human (FIH) protocols for ERT drug development programs supporting 20 Biologic License Applications (BLA) approved by the Center for Drug Evaluation and Research (CDER) at the US Food and Drug Administration (FDA) in the period of May 1994 to September 2023. We surveyed study design elements across these FIH protocols including study population, dosage form, dose selection, treatment duration, immunogenicity, biomarkers, and study follow-up. A total of 18 FIH trials from 20 BLAs were identified and of those, 72% (13/18) used single ascending dose (SAD) and/or multiple ascending dose (MAD) study design, 83% (15/18) had a primary objective of assessing the safety and tolerability, 72% (13/18) included clinical endpoint assessments, and 94% (17/18) included biomarker assessments as secondary or exploratory endpoints. Notably, the majority of ERT products tested the approved route of administration and the approved dose was tested in 83% (15/18) of FIH trials. At last, we offer considerations for the design of FIH studies.

Indexed as

Enzyme Replacement TherapyClinical Trials as TopicDrug DevelopmentHumansLysosomal Storage DiseasesPharmacology, ClinicalUnited StatesUnited States Food and Drug Administrationclinical trialdrug developmentenzyme replacement therapyfirst‐in‐humanrare disease

Identifiers

PMID38740427
PMCPMC11998121

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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.