South San Francisco, CA - February 25, 2008 - Hyperion Therapeutics, Inc. today announced that the first patient has been enrolled in a Phase 2 clinical trial of AMMONUL® (sodium phenylacetate and sodium benzoate) Injection 10%/10% in patients with Grade III or IV hepatic encephalopathy (HE). The randomized, double-blind study is designed to evaluate the safety and efficacy of AMMONUL versus standard of care in hospitalized adults. The FDA has granted AMMONUL orphan drug designation for the treatment of Grade III and IV HE.
“With no therapies currently FDA-approved, there remains considerable unmet medical need in the treatment of hepatic encephalopathy,” said Roger Williams M.D., Director of the Institute of Hepatology, University College, London. “The Phase 2 trial of AMMONUL will provide us with critical insight in systematically evaluating our hypothesis that ammonia plays an important role in the pathogenesis of this multi-factorial disease process.”
About Hepatic Encephalopathy
Hepatic encephalopathy (HE) is a serious, progressive and potentially reversible neuropsychiatric disorder caused by the accumulation of nitrous-containing toxic substances in the blood of patients with acute liver failure and chronic liver disease. Depending on disease severity, the degree of associated neurological impairment can range from mild alteration in cognitive and motor function to a rapid deterioration of consciousness level, coma, and death. The West Haven Criteria is often used to grade the mental state of HE patients with Grade 1 being the least severe (trivial lack of awareness) and Grade IV the most severe (coma).
Although the exact pathogenesis of HE remains unclear, experimental and clinical data suggest that ammonia is a contributing pathogenic factor. There are no therapies currently FDA-approved for the treatment of HE.
The active compounds of AMMONUL®, sodium phenylacetate and sodium phenylbutyrate, conjugate with glutamine and glycine respectively to provide an alternative route to urea for waste nitrogen excretion and thus attenuate the risk of ammonia and glumatine-induced toxicity. AMMONUL is currently indicated as adjunctive therapy for the treatment of acute hyperammonemia and associated encephalopathy in patients with deficiencies in enzymes of the urea cycle. In acute neonatal hyperammonemic coma, in moderate to severe episodes of hyperammonemic encephalopathy, and in episodes of hyperammonemia which fail to respond to an initial course of AMMONUL® therapy, hemodialysis is the most rapid and effective technique for removing ammonia. In such cases, the concomitant administration of AMMONUL ® can help prevent the re-accumulation of ammonia by increasing waste nitrogen excretion. Treatment of hyperammonemia also requires caloric supplementation and restriction of dietary protein; intravenous arginine is an essential component of therapy for patients with CPS, OTC, ASS, or ASL deficiency.
In patients with deficiencies in enzymes of the urea cycle, the most common adverse reactions are vomiting (9%), hypokalemia (7%), hyperglycemia (7%), convulsions (6%), and mental impairments (6%). Do not administer to patients with known hypersensitivity to sodium phenylacetate or sodium benzoate. Acute symptomatic hyperammonemia should be treated as life-threatening. Uncontrolled hyperammonemia can result in brain damage or death. Dialysis may be required, preferably hemodialysis, to remove a large burden of ammonia. Administration must be through a central line; use of a peripheral line may cause burns. Do not administer undiluted product. Because of prolonged plasma levels achieved by phenylacetate in pharmacokinetic studies, repeat loading doses should not be administered. Use caution when administering to patients with hepatic or renal insufficiency. AMMONUL may cause nausea and vomiting. An antiemetic may be administered during infusion. See the prescribing information for a complete listing of warnings, precautions, and drug interactions.
About Hyperion Therapeutics
Hyperion Therapeutics is a fully-integrated specialty therapeutics company focused on becoming a global leader in hepatology and gastrointestinal (GI) therapeutic programs and products that address orphan or underserved patient populations with unmet medical needs. The company has assembled a seasoned executive team with extensive industry experience developing and commercializing specialty pharmaceutical products. Hyperion is headquartered in South San Francisco, CA. For additional information, visit: www.hyperiontx.com.