Evidence map›Paper›PMID 36653728›Full record

ArticleThe AAPS journal2023

Model-Informed Approach Supporting Approval of Nexviazyme (Avalglucosidase Alfa-ngpt) in Pediatric Patients with Late-Onset Pompe Disease.

Ruo-Jing Li, Lian Ma, Katarzyna Drozda, Jie Wang, Ann R Punnoose, Linda J B Jeng, Janet W Maynard, Hao Zhu, Michael Pacanowski

Abstract read
PubMed Publisher
In one paragraph

Article in The AAPS journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 22% 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, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. 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

9 authors at 2 institutions in 1 country.

Ruo-Jing LiOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993, USA. Ruojing.Li@fda.hhs.gov.
Lian MaCreaterna Science and Technology, Wuhan, China.
Katarzyna DrozdaOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993, USA.
Jie WangOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993, USA.
Ann R PunnooseDivision of Rare Diseases and Medical Genetics, Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, Office of New Drug, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993, USA.
Linda J B JengDivision of Rare Diseases and Medical Genetics, Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, Office of New Drug, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993, USA.
Janet W MaynardOffice of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, Office of New Drug, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993, USA.
Hao ZhuOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993, USA.
Michael PacanowskiOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993, USA.
Center for Drug Evaluation and Research · USUnited States Food and Drug Administration · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In August 2021, the US Food and Drug Administration approved Nexviazyme (avalglucosidase alfa-ngpt) for intravenous infusion to treat patients 1 year of age and older with late-onset Pompe disease (LOPD). The effectiveness and safety were studied in patients with LOPD and patients with infantile-onset Pompe disease (IOPD). The dosage(s) tested in clinical trials was 20 mg/kg every other week (qow) in patients with LOPD and 20 mg/kg and 40 mg/kg qow in patients with IOPD. While patients 3 years old and greater with LOPD were eligible for participation in the pivotal trial, the youngest patient enrolled was 16 years old. Therefore, pediatric patients with LOPD were not well represented in the clinical trial. The prevalence of LOPD in pediatrics is extremely low. Thus, conducting a clinical trial in pediatric patients with LOPD would be challenging. Given the similar pathophysiology, mechanism of action, and disease manifestations across the age spectrum of patients with LOPD, the approved dosages for pediatric patients younger than 16 years old with LOPD were based on extrapolation of efficacy using a model-informed exposure bridging strategy, leveraging the safety data from pediatric patients with IOPD. Specifically, the exposure associated with 20 mg/kg qow in adult patients with LOPD was the target exposure for bridging of efficacy. The safety data obtained with 40 mg/kg qow in patients with IOPD was leveraged to support approval in pediatric patients with LOPD aged 1 year and older. This article illustrates a regulatory use of model-informed extrapolation approach for dose selection in pediatric patients with a rare disease.

Indexed as

Glycogen Storage Disease Type IIAdolescentAdultalpha-GlucosidasesChildChild, PreschoolHumansRare DiseasesUnited StatesUnited States Food and Drug Administrationalpha-GlucosidasesGAA protein, humanavalglucosidase alfa-ngptlate-onset Pompe diseasemodel-informed drug developmentpediatric drug developmentregulatory perspective

Identifiers

PMID36653728
OpenAlexW4317381663

What OpenQuestion holds

Textmetadata
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.