Hyperion Therapeutics Announces Presentation of Long Term Data on Ammonia Control in Pediatric Patients Treated With RAVICTI(R)

Hyperion Therapeutics Announces Presentation of Long Term Data on Ammonia
Control in Pediatric Patients Treated With RAVICTI(R) at the 12th
International Congress of Inborn Errors of Metabolism and the Urea Cycle
Disorder Satellite Symposium

SOUTH SAN FRANCISCO, Calif., Sept. 3, 2013 (GLOBE NEWSWIRE) -- Hyperion
Therapeutics, Inc. (Nasdaq:HPTX) today announced several data presentations at
the 12^th International Congress of Inborn Errors of Metabolism (ICIEM) and
the satellite symposium on urea cycle disorders (UCDs) held in Barcelona,
Spain. Among the presentations, the company highlighted long term data
regarding ammonia control in pediatric patients with UCDs who were treated
with RAVICTI® (glycerol phenylbutyrate) Oral Liquid.UCD patients lack enzymes
or transporters necessary for the conversion of ammonia to urea and experience
heightened levels of ammonia in the bloodstream. Left untreated, UCDs can
result in neurological damage, coma, and/or death.

The long term, prospectively collected, data, which were presented by Susan
Berry, M.D., Professor of Pediatrics and Division Director for Genetics and
Metabolism in the Department of Pediatrics at the University of Minnesota,
were pooled from two studies with RAVICTI which involved 49 pediatric UCD
patients less than 18 years of age, including 23 patients ages 2 months
through 5 years.During 12-months of treatment with RAVICTI, mean monthly
ammonia levels ranged from 17.2 to 24.8 umol/L and remained below the upper
limit of normal (35 umol/L). In addition, patients' physical growth and
development were similar to the normal population, as determined by Z scores
for height and weight being within one standard deviation of the normal
age-matched population. During the 12-month pre-study period, 45% of patients
reported 38 hyperammonemic crises whereas 25% experienced 17 crises during the
12 months of open-label RAVICTI dosing. Common adverse events reported were
gastrointestinal and upper respiratory tract infections.Four patients did not
complete the 12-month treatment period with RAVICTI.

Pooled analysis of data from two previously reported short term trials that
independently demonstrated RAVICTI to be non-inferior to BUPHENYL® (sodium
phenylbutyrate) (Lichter 2011, Smith 2013) were also presented.Among the 26
patients ages 2 months through 17 years enrolled in these two switchover
studies, mean daily ammonia exposure assessed as 24-hour area under the curve
was 872 vs. 627 µmol/L*h (p = 0.008) for BUPHENYL and RAVICTI
respectively.The percentage of abnormal ammonia values on BUPHENYL and
RAVICTI were 35% and 15% (p = 0.02), respectively.All patients switched from
BUPHENYL to RAVICTI in a single step and adverse events reported by more than
one patient on RAVICTI were abdominal pain and vomiting, which generally
decreased and/or resolved with continued treatment.

"Pediatric patients under the age of 18 account for approximately 60 percent
of UCD patients in the U.S." commented Dr. Berry, "and we are particularly
encouraged by the findings among young children participating in these
studies."

Also presented were analyses on both the relationship between fasting ammonia
and outcome in UCDs.The post hoc analyses of fasting ammonia involved over
1000 ammonia values from 100 clinically stable UCD patients ages 2 months to >
70 years who participated in the short term switchover and/or long term
RAVICTI treatment protocols.Fasting ammonia correlated strongly with total
daily ammonia exposure (r=0.79; 0<0.0001) assessed as 24-hour area under the
curve in the short term studies and, during long term dosing, correlated
significantly and inversely with time to first hyperammonemic crisis
(p<0.0091). After controlling for age, gender and race, patients with a
baseline fasting ammonia >1.0 x ULN experienced a rate of hyperammonemic
crises approximately 15 times higher than those with a fasting ammonia <0.5
ULN (p=0.0004).

Bruce Scharschmidt, CMO, Hyperion Therapeutics, commented, "We believe these
are important new findings which warrant further investigation and suggest
that management of UCD patients designed to achieve tight ammonia control may
result in improved ammonia control and fewer hyperammonemic crises."

RAVICTI Indications, Usage and Safety Information

RAVICTI is indicated for use as a nitrogen-binding agent for chronic
management of adult and pediatric patients ≥two years of age with urea cycle
disorders (UCDs) that 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).

Limitations of Use:

  *RAVICTI is not indicated for the treatment of acute hyperammonemia in
    patients with UCD 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.

RAVICTI is Contraindicated in Patients:

  *Less than two months of age. Children less than two months of age may have
    immature pancreatic exocrine function which could impair hydrolysis of
    RAVICTI, leading to impaired absorption of phenylbutyrate and
    hyperammonemia.
  *With known hypersensitivity to phenylbutyrate. Signs of hypersensitivity
    include wheezing, shortness of breath, coughing, low blood pressure,
    flushing, nausea and rash.

The major metabolite of RAVICTI, PAA, is associated with neurotoxicity at
levels ≥ 500 μg/mL. If symptoms of vomiting, nausea, headache, drowsiness, or
confusion are present in the absence of high ammonia or other intercurrent
illnesses, reduce the RAVICTI dosage.

Pancreatic insufficiency or intestinal malabsorption may result in reduced or
absent digestion of RAVICTI and/or absorption of phenylbutyrate and reduced
control of plasma ammonia. Monitor ammonia levels closely in these patients.

Most common adverse reactions in ≥10% of patients are: diarrhea, flatulence,
headache, nausea, vomiting, fatigue, decreased appetite, hyperammonemia,
dizziness, headache, upper abdominal (stomach) pain and rash.

Corticosteroids, valproic acid, or haloperidol may increase plasma ammonia
levels; monitor ammonia levels closely when used concomitantly with
RAVICTI.Probenecid may affect renal excretion of metabolites of RAVICTI
including PAGN and PAA.

The use of RAVICTI in pregnant women may cause fetal harm. Breastfeeding is
not recommended during RAVICTI treatment.

Please see full prescribing information for Ravicti at
(http://www.ravicti.com/files/RAVICTI_Prescribing_Information.pdf ) and
Medication Guide (http://www.ravicti.com/files/RAVICTI_Medication_Guide.pdf)
for Ravicti.

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

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®
(glycerol phenylbutyrate) Oral Liquid, was approved in February 2013 and is
currently being marketed in the United States. The company also owns and
markets BUPHENYL® (sodium phenylbutyrate) Tablets and Powder worldwide. For
more information, please visit www.hyperiontx.com.

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