The randomized, double-blind, placebo-controlled Phase 2 trial enrolled 178 patients with cirrhosis, including 59 already taking rifaximin, who had experienced two or more HE events in the prior six months. Patients were randomized in a 1:1 ratio to receive 6 mL GPB or placebo, orally, twice daily for 16 weeks. The primary endpoint was the proportion of patients with HE events. GPB significantly reduced the proportion of patients who experienced a HE event (21% compared to 36%, p=0.02), as well as the time to first HE event (hazard ratio = 0.56, p < 0.05) and total HE events (35 versus 57, p=0.04) and was associated with fewer HE hospitalizations (13 versus 25, p=0.06). Among the subgroup of patients not taking rifaximin at baseline, there was a highly statistically significant reduction among patients randomized to GPB both in the percentage of patients with events (10% versus 32%; p < 0.01) and the total number of HE events (7 versus 31; p < 0.001). Among patients taking rifaximin at baseline, there was no difference in the proportion of patients with events or total events, although a non-significant trend was observed with respect to fewer hospitalizations in patients randomized to GPB. A similar proportion of patients in the GPB (79%) and placebo group (76%) experienced adverse events.
"We and our investigators are gratified by the results and new information the trial has yielded regarding the importance of ammonia in the pathogenesis of HE. We look forward to initiating enrollment in our pivotal Phase 3 trial late this year or early 2015 with the ultimate goal of providing HE patients with a new therapeutic alternative," said
About Hepatic Encephalopathy
HE is a serious but potentially reversible neurological disorder that can occur in patients with cirrhosis of any etiology or acute liver failure. HE comprises a spectrum of neurological signs and symptoms ranging from mild (e.g. minimal disorientation) to severe (e.g. coma, death) and is believed to occur when the brain is exposed to gut-derived toxins such as ammonia that are normally removed from the blood by a healthy liver. Based on the current epidemiological data, Hyperion estimates that approximately 140,000 cirrhosis patients have overt HE.
About Glycerol Phenylbutyrate
Glycerol phenylbutyrate, is a pre-pro-drug of phenylacetic acid, the active moiety of RAVICTI® and BUPHENYL®, branded therapies currently
RAVICTI is indicated for use as a nitrogen binding agent for chronic management of adult and pediatric patients ≥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.
To the extent that statements contained in this press release are not descriptions of historical facts regarding Hyperion, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements contained in this press release include expectations about future cost of sales for RAVICTI and BUPHENYL. Hyperion undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties relating to the business of the company in general,
see Hyperion's most recent Quarterly Report on Form 10-Q filed with the
Sylvia WheelerVice President, Investor Relations (650) 745-7834
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