Ravicti Receives FDA Approval

February 1, 2012

FDA Release :

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm337639.htm

Press Release, Hyperion Therapeutics

Hyperion Therapeutics' RAVICTI(TM) (glycerol phenylbutyrate) Liquid Receives FDA Approval for Treatment of Urea Cycle Disorders

  • Anticipated market launch by end of April 2013

SOUTH SAN FRANCISCO, Calif., Feb. 1, 2013 (GLOBE NEWSWIRE) -- Hyperion Therapeutics, Inc. (Nasdaq:HPTX) today announced that the U.S. Food and Drug Administration (FDA) has approved RAVICTI for the treatment of Urea Cycle Disorders (UCD) in patients two years of age and older. The drug is expected to be commercially available by the end of April 2013.  

Separately, Hyperion announced it has received notification from the U.S. Patent & Trademark Office (USPTO) of the allowance of the claims of patent application number 13/417,137 entitled, METHODS OF THERAPEUTIC MONITORING OF NITROGEN SCAVENGING DRUGS, which discloses optimal measurement timing and target levels for blood ammonia in UCD patients. A Notice of Allowance is issued after the USPTO makes a determination that a patent can be granted from an application. The issued patent would have a term that expires in March 2032. After issuance, Hyperion plans to list this patent in FDA's Approved Drug Products with Therapeutic Equivalence, or Orange Book.   

 "With FDA approval of RAVICTI, we are now in a position to commercialize Hyperion's first product. Furthermore we believe that the allowed claims, once issued, will provide important protection for the use of RAVICTI to treat UCD," said Donald J. Santel, Hyperion's chief executive officer. "We thank our clinical trial patients, their families, our investigators and study coordinators, the UCD Consortium, and the National Urea Cycle Disorders Foundation — in particular NUCDF Executive Director Cynthia Le Mons — for their collaboration and support of our development efforts."

The FDA approval of RAVICTI was based on a New Drug Application (NDA) that included data from 10 clinical trials, including six in UCD patients, that involved 23 sites, over 50 investigators and sub-investigators, and approximately a dozen referring metabolic specialists throughout North America. As part of FDA approval, Hyperion agreed to post-marketing requirements that include: studies of RAVICTI safety, ammonia control, and pharmacokinetics in pediatric UCD patients in the first two months of life and from two months to two years of age; studies in healthy adults to examine drug-drug interaction and whether RAVICTI metabolites are present in breast milk; a randomized controlled clinical trial to assess the safety and efficacy of RAVICTI in treatment-naïve patients with UCD; and a UCD registry of approximately 10 years duration. Importantly, the FDA did not require a Risk Evaluation and Mitigation Strategy (REMS) program.

"We believe the RAVICTI development program has brought not only a promising new drug to the UCD community, but also a much deeper understanding of UCD treatment," said Dr. Bruce F. Scharschmidt, M.D., Hyperion's chief medical officer and senior vice president. "The post-marketing studies and registry represent additional opportunities to expand our knowledge in areas that are important to the community, particularly in very young children, a population in which few systematic studies have been done."

Hyperion intends to commercially launch RAVICTI by the end of April. As part of the commercialization of RAVICTI, Hyperion today announced the launch of a dedicated call center, Hyperion UCD Support Services, which will serve as an integrated resource for patients and their physicians in the areas of RAVICTI prescription intake, reimbursement adjudication, patient financial support, and ongoing compliance support. Together with distribution via two specialty pharmacies, the Company believes that its UCD Support Services program will provide better support to UCD patients, their families and their physicians and help them better manage their disease.  

RAVICTI Indications, Usage and Safety Information

RAVICTI is indicated for use as a nitrogen-binding agent for chronic management of adult and pediatric patients ≥ two years of age with urea cycle disorders (UCDs) that cannot be managed by dietary protein restriction and/or amino acid supplementation alone.  RAVICTI must be used with dietary protein restriction and in some cases, dietary supplements (e.g. essential amino acids, arginine, citrulline, protein-free calorie supplements).

Limitations of Use: 

  • RAVICTI is not indicated for the treatment of acute hyperammonemia in patients with UCD because more rapidly acting interventions are essential to reduce plasma ammonia levels.
  • The safety and efficacy of RAVICTI for the treatment of N-acetylglutamate synthase (NAGS) deficiency has not been established.

RAVICTI is Contraindicated in Patients:

  • Less than two months of age. Children less than two months of age may have immature pancreatic exocrine function which could impair hydrolysis of RAVICTI, leading to impaired absorption of phenylbutyrate and hyperammonemia.
  • With known hypersensitivity to phenylbutyrate. Signs of hypersensitivity include wheezing, shortness of breath, coughing, low blood pressure, flushing, nausea and rash.

The major metabolite of RAVICTI, PAA, is associated with neurotoxicity at levels ≥ 500 μg/mL. If symptoms of vomiting, nausea, headache, drowsiness, or confusion are present in the absence of high ammonia or other intercurrent illnesses, reduce the RAVICTI dosage.

Pancreatic insufficiency or intestinal malabsorption may result in reduced or absent digestion of RAVICTI and/or absorption of phenylbutyrate and reduced control of plasma ammonia. Monitor ammonia levels closely in these patients.

Most common adverse reactions in ≥ 10% of patients are: diarrhea, flatulence, headache, nausea, vomiting, fatigue, decreased appetite, hyperammonemia, dizziness, headache, upper abdominal (stomach) pain and rash.

Corticosteroids, valproic acid, or haloperidol may increase plasma ammonia levels; monitor ammonia levels closely when used concomitantly with RAVICTI. Probenecid may affect renal excretion of metabolites of RAVICTI including PAGN and PAA.

The use of RAVICTI in pregnant women may cause fetal harm. Breastfeeding is not recommended during RAVICTI treatment.

Please see full Prescribing Information for RAVICTI at www.hyperiontx.com.