Carglumic acid enhances rapid ammonia detoxification in classical organic acidurias with a favourable risk-benefit profile: a retrospective observational study

Orphanet Journal of Rare Diseases
Vassili ValayannopoulosAnupam Chakrapani

Abstract

Isovaleric aciduria (IVA), propionic aciduria (PA) and methylmalonic aciduria (MMA) are inherited organic acidurias (OAs) in which impaired organic acid metabolism induces hyperammonaemia arising partly from secondary deficiency of N-acetylglutamate (NAG) synthase. Rapid reduction in plasma ammonia is required to prevent neurological complications. This retrospective, multicentre, open-label, uncontrolled, phase IIIb study evaluated the efficacy and safety of carglumic acid, a synthetic structural analogue of NAG, for treating hyperammonaemia during OA decompensation. Eligible patients had confirmed OA and hyperammonaemia (plasma NH3 > 60 μmol/L) in ≥1 decompensation episode treated with carglumic acid (dose discretionary, mean (SD) first dose 96.3 (73.8) mg/kg). The primary outcome was change in plasma ammonia from baseline to endpoint (last available ammonia measurement at ≤18 hours after the last carglumic acid administration, or on Day 15) for each episode. Secondary outcomes included clinical response and safety. The efficacy population (received ≥1 dose of study drug and had post-baseline measurements) comprised 41 patients (MMA: 21, PA: 16, IVA: 4) with 48 decompensation episodes (MMA: 25, PA: 19, IVA: 4). Mean baseline ...Continue Reading

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Citations

Jul 26, 2017·Journal of Clinical Pharmacy and Therapeutics·E KoseY Ozturk
Feb 1, 2018·Nutrients·Jing LiuSeong-Tshool Hong
Nov 3, 2016·Current Opinion in Pediatrics·Jamie L Fraser, Charles P Venditti
Dec 14, 2018·Orphanet Journal of Rare Diseases·Johannes HäberleNicola Longo
Sep 10, 2020·JIMD Reports·Laura María Palomino PérezConsuelo Pedrón-Giner
May 24, 2019·Journal of Inherited Metabolic Disease·Hanneke A HaijesNanda M Verhoeven-Duif
Jan 1, 2016·Expert Review of Endocrinology & Metabolism·Cristel C Chapel-CrespoKimihiko Oishi
Feb 8, 2019·Scientific Reports·Eugeniy S ProtasovElena I Sinauridze
Aug 1, 2020·Case Reports in Pediatrics·Sinziana StanescuMercedes Martínez-Pardo Casanova
Apr 2, 2020·Case Reports in Pediatrics·Jun KidoKimitoshi Nakamura
Apr 24, 2018·Journal of Medical Case Reports·Albina TummoloFrancesco Papadia
Feb 9, 2021·Molecular Genetics and Metabolism Reports·Ertugrul KiykimAyse Cigdem Aktuglu Zeybek

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