Market Overview

Horizon Pharma plc Announces the U.S. Patent and Trademark Office Issuance of Additional Notices of Allowance With Claims Covering RAVICTI® (glycerol phenylbutyrate) Oral Liquid

Share:

- Will Represent the Tenth and Eleventh U.S. Patents to be Listed in
the Orange Book for RAVICTI -

Horizon Pharma plc (NASDAQ:HZNP) today announced that it has received
two Notices of Allowance from the United States Patent and Trademark
Office for U.S. patent application numbers 15/944,398 and 15/944,416,
both titled "Methods of Therapeutic Monitoring of Nitrogen Scavenging
Drugs" that cover Horizon's U.S. approved medicine RAVICTI (glycerol
phenylbutyrate) Oral Liquid.

These Notices of Allowance conclude the substantive examination of the
patent applications and will result in the issuance of two U.S. patents
after administrative processes are completed. The U.S. patents scheduled
to issue from these applications will expire on September 22, 2030.
After issuance, Horizon plans to list the U.S. patents in the FDA's
Approved Drug Products with Therapeutic Equivalence Evaluations, or
Orange Book.

About RAVICTI

RAVICTI was first approved in the U.S. in February 2013 for the chronic
management of adult and pediatric patients ≥2 years of age with UCDs
that cannot be managed by dietary protein restriction and/or amino acid
supplementation alone. In April 2017, the indication for RAVICTI was
expanded to include children as young as two months of age. Click here
for more information about RAVICTI.

RAVICTI® (glycerol phenylbutyrate) Oral Liquid

INDICATIONS AND USAGE

RAVICTI is a nitrogen-binding agent indicated for chronic management of
patients 2 months of age and older with urea cycle disorders (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).

LIMITATIONS OF USE

  • RAVICTI is not indicated for the treatment of acute hyperammonemia in
    patients with UCDs because 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.

DETAILED IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

  • Patients less than 2 months of age: Children less than 2 months
    of age may have immature pancreatic exocrine function, which could
    impair hydrolysis of RAVICTI, leading to impaired absorption of
    phenylbutyrate and hyperammonemia.
  • Patients with known hypersensitivity to phenylbutyrate:
    Reactions include wheezing, dyspnea, coughing, hypotension, flushing,
    nausea and rash.

WARNINGS AND PRECAUTIONS

  • Neurotoxicity: Phenylacetate (PAA), the major metabolite of
    RAVICTI, may be toxic at levels of 500 µg/mL or greater. Reduce
    RAVICTI dosage if symptoms of neurotoxicity, including vomiting,
    nausea, headache, somnolence or confusion, are present in the absence
    of high ammonia or other intercurrent illnesses.
  • Reduced phenylbutyrate absorption in pancreatic insufficiency or
    intestinal malabsorption:
    Low or absent pancreatic enzymes or
    intestinal disease resulting in fat 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.

USE IN SPECIFIC POPULATIONS

  • Pregnancy: Limited available data with RAVICTI use in pregnant
    women are insufficient to inform a drug-associated risk of major birth
    defects and miscarriage. Based on animal data, RAVICTI may cause fetal
    harm. A voluntary patient registry monitors pregnancy outcomes in
    women exposed to RAVICTI. For more information regarding the registry
    program, visit www.ucdregistry.com
    or call 1-855-823-2595.
  • Nursing mothers: Breastfeeding is not recommended during
    treatment with RAVICTI. There are no data on the presence of RAVICTI
    in human milk, the effects on the breastfed infant nor the effects on
    milk production.

ADVERSE REACTIONS

  • In ≥10% of adult patients: diarrhea, flatulence, and headache occurred
    during 4-week treatment (n=44) with RAVICTI; nausea, vomiting,
    diarrhea, decreased appetite, dizziness, headache and fatigue occurred
    during 12-month treatment (n=51) with RAVICTI.
  • In ≥10% of pediatric patients ages 2 to 17 years: upper abdominal
    pain, rash, nausea, vomiting, diarrhea, decreased appetite and
    headache occurred during 12-month treatment (n=26) with RAVICTI.
  • In ≥10% of pediatric patients ages 2 months to less than 2 years:
    neutropenia, vomiting, diarrhea, pyrexia, hypophagia, cough, nasal
    congestion, rhinorrhea, rash and papule occurred during 12-month
    treatment (n=6) with RAVICTI.

DRUG INTERACTIONS

  • Corticosteroids, valproic acid or haloperidol may increase plasma
    ammonia level. Monitor ammonia levels closely.
  • Probenecid may affect renal excretion of metabolites of RAVICTI,
    including phenylacetylglutamine (PAGN) and PAA.
  • CYP3A4 substrates with narrow therapeutic index (e.g., alfentanil,
    quinidine, cyclosporine): RAVICTI may decrease exposure to the
    concomitant drug.
  • Midazolam: Use of RAVICTI decreased exposure of midazolam with
    concomitant use.

Click here
to download a copy of the RAVICTI Full Prescribing Information.

About Urea Cycle Disorders (UCDs)

A UCD is a rare genetic disorder that affects approximately 1 in 35,000
live births in the United States. It is caused by an enzyme deficiency
in the urea cycle, a process that is responsible for converting excess
ammonia from the bloodstream and ultimately removing it from the body.
Because of this, people with a UCD experience hyperammonemia, or
elevated ammonia levels in their blood, that can then reach the brain
and cause irreversible brain damage, coma or death. UCD symptoms may
first occur at any age depending on the severity of the disorder, with
more severe defects presenting earlier in life.

About Horizon Pharma plc

Horizon Pharma plc is focused on researching, developing and
commercializing innovative medicines that address unmet treatment needs
for rare and rheumatic diseases. By fostering a growing pipeline of
medicines in development and exploring all potential uses for currently
marketed medicines, we strive to make a powerful difference for
patients, their caregivers and physicians. For us, it's personal: by
living up to our own potential, we are helping others live up to theirs.
For more information, please visit www.horizonpharma.com,
follow us @HZNPplc on
Twitter or like us on Facebook.

Forward-Looking Statements

This press release contains forward-looking statements, including
statements regarding the issuance of patents based on the Notices of
Allowance from the U.S. Patent and Trademark Office, the expected term
of the patents, if issued, potential patent protection for RAVICTI and
plans to list newly issued patents in the FDA's Orange Book. These
forward-looking statements are based on management expectations and
assumptions as of the date of this press release, and actual results may
differ materially from those in these forward-looking statements as a
result of various factors. These factors include risks regarding whether
the administrative processes required for the issuance of patents as
indicated in the Notices of Allowance will be completed in a timely
manner or at all, whether the patents, if issued as indicated in the
Notices of Allowance, will provide sufficient protection and market
exclusivity for RAVICTI, whether any patents covering RAVICTI may be
challenged, invalidated, infringed or circumvented by third parties and
other factors described in Horizon's filings with the United States
Securities and Exchange Commission, including those factors discussed
under the caption "Risk Factors" in those filings. Forward-looking
statements speak only as of the date of this press release and Horizon
does not undertake any obligation to update or revise these statements,
except as may be required by law.

View Comments and Join the Discussion!