Horizon Pharma Announces That Health Canada Determines RAVICTI (Glycerol Phenylbutyrate) Oral Liquid Is Eligible For Data Protection

DUBLIN, IRELAND--(Marketwired - February 22, 2016) - Horizon Pharma plc (NASDAQ: HZNP), a biopharmaceutical company focused on improving patients' lives by identifying, developing, acquiring and commercializing differentiated and accessible medicines that address unmet medical needs, today announced that the Therapeutic Products Directorate of Health Canada has determined that RAVICTI® (Glycerol Phenylbutyrate) Oral Liquid is eligible for data protection as it is an "innovative drug" as defined by section C.08.004.1 Food and Drug Regulations.

Subject to final review, if the RAVICTI New Drug Submission (NDS) receives a notice of compliance, RAVICTI would be added to the Register of Innovative Drugs and receive data protection for a term of eight years from the date of the issuance of the notice of compliance. The RAVICTI NDS was originally filed on April 24, 2014 and has been the subject of a stay since June 12, 2015 pending a final determination on data protection.

"This decision is a significant step toward making RAVICTI available in Canada and we look forward to reinitiating the regulatory review process in order to get this innovative medicine to the approximately 100 patients who have urea cycle disorders and who may benefit from treatment as quickly as possible," said Jared Rhines, vice president and general manager, Canada, LATAM and APAC, Horizon Pharma plc.

About RAVICTI®
RAVICTI was approved by the U.S. Food and Drug Administration in February 2013 for chronic management of UCDs in adult and pediatric patients greater or equal to 2 years of age 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 and protein-free calorie supplements). RAVICTI is also indicated for use in all 28 Member States of the European Union and 3 Member States of the European Economic Area as a nitrogen-binding agent for chronic management of adult and pediatric patients two months of age and older with UCDs who cannot be managed by dietary protein restriction and/or amino acid supplementation alone.

Important Safety Information

LIMITATIONS OF USE:

  • 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

CONTRAINDICATIONS:

  • In patients less than 2 months of age
  • In patients who develop or have known hypersensitivity to phenylbutyrate

WARNINGS AND PRECAUTIONS:

  • Phenylacetate (PAA), the major metabolite of RAVICTI, may be toxic at levels ≥500 µg/mL. Reduce RAVICTI dosage if symptoms of neurotoxicity, including vomiting, nausea, headache, somnolence, confusion, or sleepiness are present in the absence of high ammonia or other intercurrent illnesses.
  • 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.
  • RAVICTI should be used with caution in patients who are pregnant or planning to become pregnant. Based on animal data it may cause fetal harm. A voluntary patient registry will include evaluation of pregnancy outcomes in patients with UCDs. For more information regarding the registry program, visit www.ucdregistry.com or call 1-855-823-2592
  • Caution should be exercised when administering RAVICTI to nursing mothers, as breastfeeding is not recommended with maternal use of RAVICTI. It is not known whether RAVICTI or its metabolites are present in breast milk

ADVERSE REACTIONS:

  • Adverse reactions occurring in ≥ 10% of adult patients during short-term treatment (n=44, 4 weeks) with RAVICTI were diarrhea, flatulence, and headache.
  • Adverse reactions occurring in ≥ 10% of adult patients during long-term treatment (n=51, 12 months) with RAVICTI were nausea, vomiting, diarrhea, decreased appetite, hyperammonemia, dizziness, headache, and fatigue.
  • Adverse events occurring in ≥ 10% of pediatric patients during long-term treatment (n=26, 12 months) with RAVICTI were upper abdominal pain, rash, nausea, vomiting, diarrhea, decreased appetite, hyperammonemia, and headache

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 PAGN and PAA

About Urea Cycle Disorders (UCDs)
Urea Cycle Disorders or UCDs are inherited metabolic diseases caused by a deficiency of one of the enzymes or transporters that constitute the urea cycle. The urea cycle involves a series of biochemical steps in which ammonia, a potent neurotoxin, is converted to urea, which is excreted in the urine. UCD patients may experience episodes where they get symptoms from the ammonia in their blood being excessively high -- called hyperammonemic crises -- which may result in 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 a biopharmaceutical company focused on improving patients' lives by identifying, developing, acquiring and commercializing differentiated and accessible medicines that address unmet medical needs. The Company markets nine medicines through its orphan, primary care and rheumatology business units. Horizon's global headquarters are in Dublin, Ireland. For more information, please visit www.horizonpharma.com. Follow @HZNPplc on Twitter or view careers on our LinkedIn page.

Forward-Looking Statements
This press release contains forward-looking statements, including statements regarding the potential availability of data protection if a notice of compliance is received from Health Canada, the expected term of the data protection, if granted, the potential for RAVICTI to receive a notice of compliance, Horizon Pharma's plans to reinitiate the regulatory review process for RAVICTI in Canada and the potential availability of RAVICTI in Canada. 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 regulatory approval will be completed in a timely matter or at all, whether a notice of compliance is issued with respect to the RAVICTI NDS, whether the data protection, if granted as indicated in the Food and Drug Regulations, will provide sufficient protection and market exclusivity for RAVICTI in Canada, whether data protection covering RAVICTI may be challenged, invalidated, infringed or circumvented by third parties, Horizon Pharma's ability to defend data protection challenges related to RAVICTI, Horizon's ability to successfully market RAVICTI in Canada if a notice of compliance is issued, 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.


Contacts:
Investors:
John Thomas
Executive Vice President, Strategy and Investor Relations
Investor-relations@horizonpharma.com

Tina Ventura
Vice President, Investor Relations
investor-relations@horizonpharma.com

U.S. Media:
Geoff Curtis
Senior Vice President, Corporate Communications
gcurtis@horizonpharma.com

Ireland Media:
Ray Gordon
Gordon MRM
ray@gordonmrm.ie

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