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The treatment is the first approved medication for this patient population.
The US Food and Drug Administration (FDA) has approved carglumic acid (CARBAGLU) tablets 200 mg for the treatment of acute hyperammonemia associated with propionic acidemia and methylmalonic acidemia.
The approval allows Recordati Rare Diseases to move forward with the treatment as an adjunctive therapy to standard of care for both pediatric and adult patients.
Carglumic acid represents the first and only approved medication for acute hyperammonemia because of propionic acidemia and methylmalonic acidemia.
The drug was initially approved for N-acetylglutamate synthase (NAGS) deficiency, another rare metabolic disorder, as adjunctive therapy to standard of care for the treatment of acute hyperammonemia due to NAGS deficiency, and maintenance therapy for the treatment of chronic hyperammonemia due to NAGS deficiency.
PA and MMA are both rare inherited metabolic disorders that cause dysfunction of a specific step of amino acid catabolism or breaking down of certain fatty acids because of deficient enzyme activity. This results in toxic metabolites to accumulate, causing hyperammonemia.
The treatment acts a replacement for N-acetylglutamate (NAG) in NAGS deficiency, PA, and MMA patients by activating carbamoyl phosphate synthetase (CPS 1), improves or restores the function of the urea cycle, and facilitates ammonia detoxification and urea production.
The approval is based on the results of a randomized, double-blind, placebo-controlled, multicenter trial comparing the study drug to placebo in PA or MMA patients with hyperammonemic episodes.
The efficacy profile was based on 90 hyperammonemic episodes for 24 patients, showing that patients who received carglumic acid demonstrated a quicker reduction of ammonia compared to the placebo group.
The researchers sought primary endpoints of the time from the first dose to the earlier of blood ammonia level below 50 micromol/L or hospital discharge. Throughout the first 3 days of treatment there was a higher proportion of carglumic acid patients that reached the primary endpoint.
There was also at least 1 adverse reaction reported by 42.2% of the 90 hyperammonemic episodes that occurred, with the most common events being neutropenia, anemia, vomiting, electrolyte imbalance, decreased appetite, hypoglycemia, lethargy/stupor, encephalopathy, and pancreatitis/lipase increased.
"There are few approved drugs that treat hyperammonemia, and none that are indicated for the treatment of acute hyperammonemia in PA and MMA patients," said Mendel Tuchman, MD, Medical Geneticist and Professor Emeritus of Pediatrics at The George Washington University School of Medicine and Health Science, in a statement. "Carbaglu has the potential to impact these patients by reducing high plasma ammonia levels during critical situations."