BETHESDA, MD 01 February 2013—FDA today announced it approved the marketing of glycerol phenylbutyrate, or Ravicti, for the chronic management of certain urea cycle disorders in patients age 2 years or older.
The agency said the drug is intended for use by patients whose urea cycle disorder cannot be managed by just a protein-restricted diet or amino acid supplements.
Hyperion Therapeutics Inc., which will market the drug, has described it as "a pre-pro-drug" of the active moiety of Buphenyl.
Buphenyl contains sodium phenylbutyrate and was approved in 1996 as add-on therapy in the chronic management of patients with urea cycle disorders involving deficiencies of carbamoyl phosphate synthetase, ornithine transcarbamylase, or argininosuccinic acid synthetase.
Those enzymes are three of the six in the urea cycle, the series of reactions that converts ammonia to urea. Without this conversion, ammonia can accumulate in the bloodstream and ultimately damage the brain.
Ravicti, its labeling (PDF) states, is a liquid that patients ingest with food three times a day. Doses are to be administered directly into a patient's mouth, nasogastric tube, or gastrostomy tube. Each milliliter provides 1.02 g of phenylbutyrate.
FDA said the major study of glycerol phenylbutyrate showed that it was as effective as sodium phenylbutyrate in controlling blood ammonia concentrations in 44 adults who were already using the latter drug.
The labeling recommends an initial dosage of 4.5–11.2 mL/m2/day in patients not already using a phenylbutyrate product. For patients who have been using sodium phenylbutyrate, health care providers should multiply the dosage of that drug, in grams, by 0.86 to determine the dosage of glycerol phenylbutyrate in milliliters and then switch the therapy. All dosages are to be given in three equal doses, rounded up to the nearest 0.5 mL, during the day and not exceed a total of 17.5 mL/day.
Glycerol phenylbutyrate is contraindicated in children less than two months of age and patients with a known hypersensitivity to phenylbutyrate.
FDA said diarrhea, flatulence, and headache were among the most common adverse effects of glycerol phenylbutyrate therapy during studies that included patients as young as age 2 years.
Hyperion said it expects Ravicti to be commercially available by the end of April.
Two specialty pharmacies will distribute the product, the company said.
Ravicti will be available in multiple-use 25-mL glass bottles, one or four to a carton. The bottles should be stored at 20–25 °C.
There is a medication guide for the product.
Hyperion in March 2012 acquired the rights to glycerol phenylbutyrate from Ucyclyd Pharma Inc., which markets Buphenyl. At the time, Hyperion said it had an option to acquire the rights to that product in the first half of 2013.