The Food and Drug Administration (FDA) has approved a new indication for Carbaglu® (carglumic acid; Recordati Rare Diseases) for use as adjunctive therapy in the treatment of acute hyperammonemia due to propionic acidemia (PA) or methylmalonic acidemia (MMA), rare inherited metabolic disorders caused by deficiencies in the enzymes propionyl-CoA carboxylase and methylmalonyl-CoA mutase, respectively.

Carbaglu facilitates ammonia detoxification and urea production by activating carbamoyl phosphate synthetase 1, thereby improving or restoring the function of the urea cycle. The approval was based on data from a double-blind, placebo-controlled phase 2 trial that compared the efficacy of Carbaglu to placebo in 24 patients with PA (n=15) and MMA (n=9).

Patients were randomly assigned to receive either Carbaglu or placebo in addition to standard of care for 7 days or until hospital discharge, whichever occurred earlier. The primary end point was the time from the first dose of drug to the earlier of plasma ammonia level less than or equal to 50micromol/L or hospital discharge.

The efficacy evaluation was based on 90 hyperammonemic episodes (42 treated with Carbaglu and 48 with placebo). Results showed that a higher proportion of Carbaglu-treated episodes reached the primary end point compared with placebo-treated episodes. Patients in the Carbaglu arm reached the primary end point at a median time of 1.5 days compared with 2.0 days in the placebo arm (difference 0.5 days; 95% CI, -1.2, 0.1). 

The most common adverse reactions reported with Carbaglu (incidence of greater than or equal to 5%) were neutropenia, anemia, vomiting, electrolyte imbalance, decreased appetite, hypoglycemia, lethargy/stupor, encephalopathy and increased pancreatitis/lipase.

Carbaglu is also indicated as adjunctive therapy for the treatment of acute hyperammonemia due to N-acetylglutamate synthase (NAGS) deficiency and as maintenance therapy for chronic hyperammonemia due to NAGS deficiency.

The product is supplied as 200mg strength tablets for oral suspension in 5- and 60-count bottles.


1.    Recordati Rare Diseases: Carbaglu® (carglumic acid) tablets 200mg receives U.S. FDA approval for a new indication to treat acute hyperammonemia associated with propionic acidemia and methylmalonic acidemia. [press release]. Lebanon, NJ: Recordati Rare Diseases; January 26, 2021. 

2.    Carbaglu [package insert]. Lebanon, NJ: Recordati Rare Diseases; 2021.