Monday, November 12, 2012

AASLD-HALT-HE Study Underscores Role of Ammonia in Hepatic Encephalopathy

HALT-HE Study Underscores Role of Ammonia in Hepatic Encephalopathy

Hyperion Reports Phase 2 Study Results at AASLD Plenary Session

Hyperion Therapeutics, Inc. (Nasdaq:HPTX) announced today that the results of the Phase 2 HALT-HE Study were presented at the Presidential Plenary Session I of the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) (The Liver Meeting®), in Boston, MA.

Principal Investigator Don Rockey, Chief of Medicine at the Medical University of South Carolina delivered an oral presentation entitled, Randomized, controlled, double-blind study of glycerol phenylbutyrate in patients with cirrhosis and episodic hepatic encephalopathy.

Dr. Rockey explained, "The study results provide new insight into the importance of ammonia in the pathogenesis of hepatic encephalopathy (HE). Based on its safety profile, Hyperion's investigational drug, glycerol phenylbutyrate (GPB), or "Ravicti", shows promise as a novel therapeutic agent."

Dr. Rockey explained,

  • The study met its primary endpoint: significantly fewer patients in the active arm experienced HE events - 21% vs. 36% (p = 0.021).
  • Compared to placebo, patients randomized to GPB also had significantly fewer total HE events (35 vs. 57 p=0.035), significantly lower ammonia values (46 vs. 58 umol/L p=0.036), and significantly fewer symptomatic days (13 vs. 27; p=0.015).
  • There were non-statistically significant trends in favor of fewer HE-hospitalizations and fewer total HE-hospital days.
  • Safety appeared satisfactory (76% and 79% of subjects in the placebo and GPB groups, respectively, reported AEs) and the adverse event profile was consistent with that expected for the study population.
  • Ammonia was significantly lower on GPB (45.7 vs. 58.15 umol/L, p = 0.036) and correlated with the likelihood of HE events whether measured at baseline or during the study (p < 0.01)
The study enrolled 178 total patients, of whom 59 were on Rifaximin at baseline, including 29 in the placebo arm and 30 in the active arm. Among the 119 patients not on Rifaximin at baseline, there was a highly statistically significant reduction among GPB treated patients in both the percentage of patients with events (10% vs 32%; p=0.003) as well as the total number of HE events (7 vs. 31; p<0.001). Among patients on Rifaximin at baseline, there was no difference in the number of patients with events or total events. Ammonia was similarly lowered on GPB among patients taking (67 vs. 91 umol/L; p=0.13) or not taking (36 vs. 43 umol/L; p=0.08), although the differences were not statistically significant due to the smaller sample size. Patients on Rifaximin at baseline had higher ammonia levels than those not on Rifaximin.

The abstract is published online at The HALT-HE study was a Phase II, multi-center, randomized, double-blind trial of glycerol phenylbutyrate vs. placebo in 178 patients with episodic HE recruited from 28 sites in the United States, 9 sites in Russia and 7 sites in Ukraine. 88 patients were randomized to the placebo group and 90 to the GPB arm. The 178 patients enrolled constituted the intention to treat and safety populations. 55 patients in the GPB arm and 67 patients in the placebo arm completed the study. The population was well balanced with respect to lactulose and Rifaximin use, prior HE history and MELD score.

Hyperion also indicated that it was hosting and webcasting an analyst and investor briefing to recap the Plenary Session presentation tonight, November 12, 2012, in Boston, MA at from 6:30 p.m. — 7:30 p.m. ET in the Commonwealth Room of the Sheraton Hotel, connected to the Boston Hynes Convention Center. The webcast can be accessed from Hyperion's website in the Investors tab, under Events.

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 literature, Hyperion estimates that there are approximately one million patients in the United States with cirrhosis, of whom approximately 140,000 have overt HE.

About Glycerol Phenylbutyrate

Glycerol phenylbutyrate, an investigational drug, is a pre-pro-drug of phenylacetic acid, the active moiety of BUPHENYL®, the only branded therapy currently FDA-approved as adjunctive therapy for the chronic management of patients with the most prevalent urea cycle disorders. Glycerol phenylbutyrate holds orphan product designations in the United States and Europe for the maintenance treatment of patients with urea cycle disorders (UCD) and in the United States for the intermittent or chronic treatment of patients with cirrhosis and any grade of hepatic encephalopathy.

About Hyperion Therapeutics

Hyperion Therapeutics is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat disorders in the areas of orphan diseases and hepatology. Hyperion Therapeutics is developing Ravicti™ (glycerol phenylbutyrate) for two orphan indications: UCD and HE.

BUPHENYL® is a registered trademark of Ucyclyd Pharma, Inc.

Forward-Looking Statements:

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. Examples of forward-looking statements contained in this press release include, among others, statements regarding our expectations regarding the timing of the presentation of the results of the HALT-HE study in November. 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 Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 7 and any subsequent filings with the Securities and Exchange Commission.

CONTACT: Shari Annes, Investor Relations
         Telephone: 650 888 0902

Source: Hyperion Therapeutics, Inc.

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