FDA Approves Carglumic Acid Therapy for Rare Genetic Disorder

Yael Waknine

March 19, 2010

March 19, 2010 — The US Food and Drug Administration (FDA) has approved carglumic acid dispersible tablets (Carbaglu, Orphan Europe, a Recordati company) for treatment of a rare genetic disoder N-acetylglutamate synthase deficiency, which causes hyperammonemia.

This deficiency is a rare autosomal genetic disorder characterized by extremely high ammonia plasma levels that can cause permanent and irreversible central nervous system damage. Symptoms start shortly after birth, leading to cerebral edema, coma, and death if immediate detection and treatment do not take place.

Carglumic acid is a structural analogue of N-acetylglutamate, which is the naturally occurring activator of carbamoyl phosphate synthetase, the first enzyme of the urea cycle.

Early treatment with carglumic acid can allow patients to experience normal growth and neurological development, company officials noted in a news release.

FDA approval was based on data from a study of 23 patients who received carglumic acid therapy for periods ranging from 6 months to 21 years. Results showed that treatment decreased ammonia plasma levels within 24 hours and led to normal levels within 3 days.

Adverse events included vomiting, abdominal pain, fever, tonsillitis, anemia, ear infection, diarrhea, headache, and inflammation of the nose and throat.

Carglumic acid should only be administered by clinicians experienced in treating metabolic disorders, FDA officials said in an agency news release.

Treatment may be initiated as early as the first day of life with an initial dose of 100 to 250 mg/kg/day in 2 to 4 divided doses, and then adjusted to maintain normal ammonia plasma levels. Maintenance doses range from 10 to 100 mg/kg/day. Concomitant use of other ammonia-lowering therapies is recommended during episodes of acute hyperammonemia.

European prescribing information advises regular monitoring of liver, renal, and cardiac functions, as well as hematologic parameters. Protein restriction and arginine supplementation may be indicated in the event of low protein tolerance.

"We are very excited that more drugs are being developed to treat very rare but often devastating genetic disorders" said Janet Woodcock, MD, director of FDA's Center for Drug Evaluation and Research. "We hope to see continuing progress in this area."

Carglumic acid previously was approved by the European Commission in 2003.

As with all approved products, the FDA will continue to monitor the safety of carglumic acid for treating N-acetylglutamate synthase–related hyperammonemia. Adverse events associated with its use should be reported to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at https://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.