Interim analyses of a first-in-human phase 1/2 mRNA trial for propionic acidaemia

Dwight Koeberl, Andreas Schulze, Neal Sondheimer, Gerald S. Lipshutz, Tarekegn Geberhiwot, Lerong Li, Rajnish Saini, Junxiang Luo, Vanja Sikirica, Ling Jin, Min Liang, Mary Leuchars and Stephanie Grunewald ()
Additional contact information
Dwight Koeberl: Duke University School of Medicine
Andreas Schulze: Hospital for Sick Children and University of Toronto
Neal Sondheimer: Hospital for Sick Children and University of Toronto
Gerald S. Lipshutz: University of California at Los Angeles (UCLA)
Tarekegn Geberhiwot: University of Birmingham
Lerong Li: Inc.
Rajnish Saini: Inc.
Junxiang Luo: Inc.
Vanja Sikirica: Inc.
Ling Jin: Inc.
Min Liang: Inc.
Mary Leuchars: Inc.
Stephanie Grunewald: NIHR Biomedical Research Centre

Nature, 2024, vol. 628, issue 8009, 872-877

Abstract: Abstract Propionic acidaemia is a rare disorder caused by defects in the propionyl-coenzyme A carboxylase α or β (PCCA or PCCB) subunits that leads to an accumulation of toxic metabolites and to recurrent, life-threatening metabolic decompensation events. Here we report interim analyses of a first-in-human, phase 1/2, open-label, dose-optimization study and an extension study evaluating the safety and efficacy of mRNA-3927, a dual mRNA therapy encoding PCCA and PCCB. As of 31 May 2023, 16 participants were enrolled across 5 dose cohorts. Twelve of the 16 participants completed the dose-optimization study and enrolled in the extension study. A total of 346 intravenous doses of mRNA-3927 were administered over a total of 15.69 person-years of treatment. No dose-limiting toxicities occurred. Treatment-emergent adverse events were reported in 15 out of the 16 (93.8%) participants. Preliminary analysis suggests an increase in the exposure to mRNA-3927 with dose escalation, and a 70% reduction in the risk of metabolic decompensation events among 8 participants who reported them in the 12-month pretreatment period.

Date: 2024
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41586-024-07266-7 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:628:y:2024:i:8009:d:10.1038_s41586-024-07266-7

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-024-07266-7

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().