FDA Clears Drug for Urea Cycle Disorders

Megan Brooks

February 01, 2013

The US Food and Drug Administration (FDA) today approved glycerol phenylbutyrate (Ravicti, Hyperion Therapeutics) for the chronic management of some urea cycle disorders (UCDs) in patients aged 2 years and older.

A UCD is a genetic disorder caused by a mutation that results in a deficiency of 1 of the 6 enzymes in the urea cycle. The deficiency ultimately leads to a build-up of ammonia in the blood, which can be fatal. According to the National Urea Cycle Disorders Foundation, the estimated incidence of UCDs is 1 in 8500 births.

Glycerol phenylbutyrate, a liquid taken 3 times a day with meals, helps rid the body of ammonia.

The FDA said the drug is intended for patients whose UCD cannot be managed by a protein-restricted diet or amino acid supplements alone. It must be used with a protein-restricted diet and, in some cases, dietary supplements.

"Ravicti provides another treatment for chronic management of urea cycle disorders, a group of life-threatening conditions," Donna Griebel, MD, director of the Division of Gastrointestinal and Inborn Errors Products in the FDA's Center for Drug Evaluation and Research, said in an agency news release.

"The approval of this new therapeutic option demonstrates FDA's commitment to providing treatments for patients suffering from rare diseases," she added. The drug also was granted orphan product designation because it is intended to treat a rare disease.

The FDA said the drug's safety and effectiveness was demonstrated in a study involving 44 adults who had been using sodium phenylbutyrate (Buphenyl, Ucyclyd Pharma), another FDA-approved drug to control UCDs. Patients were randomly assigned to take Buphenyl or Ravicti for 2 weeks before being switched to the other product for an additional 2 weeks.

Ravicti proved as effective as Buphenyl in controlling ammonia levels, the agency said. Three additional studies in children and adults provided evidence supporting the long-term safety and effectiveness of Ravicti in patients ages 2 years and older.

The most common adverse effects in patients treated with glycerol phenylbutyrate include diarrhea, flatulence, and headache.