Hyperion Therapeutics Inc. received orphan product designation for its HPN-100 from the US Food and Drug Administration for maintenance treatment of patients with enzymes of the urea cycle. The company, which recently announced results from its phase II study, intends to initiate a phase III clinical programme in this indication in the second half of 2009.
HPN-100 is a pre-pro-drug of phenylacetic acid which is the active moiety of Buphenyl, the only therapy currently FDA-approved as adjunctive therapy for the chronic management of patients with the most prevalent urea cycle deficiencies including those related to carbamylphosphate synthetase, ornithine transcarbamylase and argininosuccinic acid synthetase. HPN-100 is dosed orally in liquid form.
"Receiving orphan drug designation for HPN-100 in the treatment of urea cycle disorders is an important milestone and provides meaningful benefits to the company as we work to complete clinical trials for this investigational compound," commented Donald Santel, chief executive officer of Hyperion Therapeutics.
"The designation of HPN-100 as an orphan drug for the treatment of urea cycle disorders recognizes the unmet need that remains in this patient population," said Cindy LeMons, executive director of the National Urea Cycle Disorders Foundation (NUCDF). "We are encouraged by this designation and look forward to initiation of the phase III clinical trials."
Urea cycle disorders are inherited, inborn errors of metabolism present in an estimated 1 in 10,000 births in the United States. Patients with urea cycle disorders are deficient in one of the key enzymes that comprise the urea cycle, the body's primary vehicle for removing ammonia, a potent neurotoxin, from the bloodstream. Onset may occur at any age depending on the severity of the disorder. Left untreated, urea cycle disorders can cause dangerously heightened levels of ammonia in the bloodstream (hyperammonemia) resulting in brain damage, coma, and/or death.
The National Urea Cycle Disorders Foundation is a nationally-recognized non-profit organization dedicated to saving children and adults from the catastrophic effects of urea cycle disorders. The Foundation is a lifeline to families and medical professionals all over the world desperately seeking crisis intervention and treatment information.
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.
Hyperion Therapeutics is a privately held specialty therapeutics company focused on the development of therapies that address critical unmet needs and underserved patient populations in the areas of gastroenterology and hepatology.