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Hyperion Therapeutics Announces Ravicti and Buphenyl Pharmacokinetic Analyses

Hyperion Therapeutics Announces RAVICTI and BUPHENYL Pharmacokinetic Analyses Reported in The Journal of Clinical Pharmacology

SOUTH SAN FRANCISCO, Calif., June 18, 2013 (GLOBE NEWSWIRE) -- Hyperion Therapeutics, Inc. (Nasdaq:HPTX) today announced that population pharmacokinetic (PK) modeling and dosing simulations were reported in The Journal of Clinical Pharmacology based on data from four Phase 2 and 3 trials that collectively enrolled patients with urea cycle disorders (UCDs) ages 2 months to 72 years. The final model described the differences in absorption rate and pharmacokinetic profiles of the company's two drugs, RAVICTI(R) (glycerol phenylbutyrate) Oral Liquid and BUPHENYL(R) (sodium phenylbutyrate) Tablets and Powder, in patients with UCDs. The article is available through the Wiley online library (http://onlinelibrary.wiley.com/doi/10.1002/jcph.92/abstract).

UCDs represent a collection of inherited enzyme and transporter deficiencies that impair the synthesis of urea, the body's vehicle for waste nitrogen removal via the urine, which results in affected patients suffering from high systemic levels of ammonia, a potent neurotoxin. Since UCDs constitute an ultra-orphan population with an estimated U.S. patient pool of approximately 1000, population PK modeling and dosing simulations were performed to help define the clinical pharmacology of the two compounds as well as metabolite exposure in pediatric and adult UCD patients.

The final model helps explain differences in the level of plasma metabolites (drug breakdown products) during dosing of the two drugs based on differences in the amount of drug metabolized to phenylacetylglutamine prior to reaching the systemic circulation.
Moreover, during dosing with RAVICTI as compared with BUPHENYL, phenylbutyric acid is absorbed 70-75% more slowly and blood metabolite levels generally show less fluctuation.

"These modeling data are particularly interesting in that the slower input of the active ingredient into the circulation with RAVICTI as compared with the bolus type drug release of BUPHENYL may allow for more sustained ammonia control," said Dr. George Diaz, Associate Professor, Department of Genetics & Genomic Sciences, Mount Sinai School of Medicine.

Bruce Scharschmidt, MD, Hyperion's chief medical officer added, "This work represents an outstanding example of how population PK modeling and dosing simulations can be used to help understand the behavior of drugs for patients with rare diseases in which large trials are not feasible. We are pleased to provide the UCD community with options to treat this serious disease. Specifically, with our launch of RAVICTI earlier this year, patients now have access to an important new option."

BUPHENYL tablet daily dosing requirements may be as much as 40 tablets per day while the maximum daily dose for newly-approved RAVICTI is approximately three teaspoons.

About BUPHENYL (sodium phenylbutyrate) Tablets and Powder

BUPHENYL is indicated as adjunctive therapy in the chronic management of patients with urea cycle disorders involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). BUPHENYL should not be administered to patients with known hypersensitivity to sodium phenylbutyrate or any component of this preparation. The most common adverse reactions associated with BUPHENYL were amenorrhea dysfunction, decreased appetite, body odor (probably caused by its metabolite
phenylacetate) and bad taste or taste aversion. Patients with urea cycle disorders should not take valproic acid, haloperidol, or steroids as these drugs have been reported to increase blood ammonia levels, and probenecid may affect the kidneys' excretion. Use with great care, if at all, in patients with congestive heart failure or severe renal insufficiency, and in clinical states where there is sodium retention with edema. Use caution when administering to patients with hepatic or renal insufficiency or inborn errors of beta oxidation. The safety or efficacy of doses in excess of 20 grams (40 tablets) per day has not been established.

Please see full Prescribing Information for BUPHENYL at http://hyperiontx.com/buphenyl

RAVICTI Safety Information

RAVICTI is indicated for use as a nitrogen-binding agent for chronic management of adult and pediatric patients greater than or equal to 2 years of age with UCDs who 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). RAVICTI is not indicated for the treatment of acute hyperammonemia in patients with UCDs 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.
The use of RAVICTI in patients < 2 months of age is contraindicated.

For additional Important Safety Information, including Warnings and Precautions, Adverse Events, Drug Interactions, and Special Populations, please see full Prescribing Information
(http://www.ravicti.com/files/RAVICTI_Prescribing_Information.pdf) and Medication Guide
(http://www.ravicti.com/files/RAVICTI_Medication_Guide.pdf) for RAVICTI.

About Hyperion Therapeutics

Hyperion Therapeutics, Inc. is a commercial stage biopharmaceutical company committed to developing and delivering life-changing treatments for orphan diseases and hepatology. The company's first commercial product, Ravicti(R) (glycerol phenylbutyrate) Oral Liquid, was approved in February 2013 and is currently being marketed in the United States.
For more information, please visit www.hyperiontx.com.

CONTACT: Sylvia Wheeler
         Vice President, Investor Relations
         (650) 745-7834
 

Posted: June 2013

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