Effect of carglumic acid with or without ammonia scavengers on hyperammonaemia in acute decompensation episodes of organic acidurias.

Background: Hyperammonaemia is a key sign of decompensation in organic acidurias (OAs) and can contribute to severe neurological complications, thus requiring rapid treatment.

Methods: A post-hoc analysis of two retrospective studies analysed the efficacy of carglumic acid ± ammonia (NH) scavengers compared with scavengers alone for reducing plasma NH levels in patients with OAs and hyperammonaemia (plasma NH > 60 μmol/L) during decompensation episodes. NH was analysed in 12-h periods at 0-48 h and 24-h periods at 48-120 h. Treatment-emergent adverse events (TEAEs) were recorded.

Results: Of 98 episodes, 38 were treated with carglumic acid (34 patients), 33 with NH scavengers (22 patients) and 27 with carglumic acid combined with NH scavengers (27 patients). Overall, 45% (carglumic acid group), 46% (NH scavengers group) and 74% (combination group) of episodes occurred in neonates. Median episode duration was 6 days for the carglumic acid and combination groups, and 9 days for the NH scavenger group. Median baseline NH level was: 199 μmol/L, carglumic acid; 122 μmol/L, NH scavengers; and 271 μmol/L, combination; 13, 30 and 11% of episodes required extracorporeal detoxification (ED), respectively. Data were censored at ED initiation. While baseline NH levels were higher in the combination and carglumic acid groups, mean reduction in NH levels to 72 h in both groups was greater than the NH scavengers' group; reductions were greatest in the combination group. Mean change in plasma NH vs baseline in the carglumic acid, NH scavengers and combination groups, respectively, was - 13, + 12% and - 27% at 0-12 h (p < 0.05 NH scavengers vs combination); - 47, - 22% and - 52% at 12-24 h (not significant); - 44, - 5% and - 61% at 24-48 h; and - 66, - 16% and - 76% at 48-72 h (p < 0.05 carglumic acid/combination groups vs NH scavengers for both timepoints). The number of TEAEs was similar between groups and mainly related to the disease/condition.

Conclusions: Carglumic acid is a well-tolerated and efficacious treatment for OA decompensation episodes. When given alone or combined with NH scavengers, the reduction in NH was greater than with NH scavengers alone in the first 72 h.