SOURCE: Horizon Pharma plc

Horizon Pharma plc

September 25, 2015 08:00 ET

Horizon Pharma plc Receives Positive CHMP Opinion for RAVICTI® (Glycerol Phenylbutyrate) Oral Liquid for the Treatment of Urea Cycle Disorders in Patients Greater Than Two Months of Age

DUBLIN, IRELAND--(Marketwired - Sep 25, 2015) - 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, and its affiliate Horizon Therapeutics Limited today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion at its plenary monthly meeting in September recommending  a centralized marketing authorization for RAVICTI® (glycerol phenylbutyrate) Oral Liquid for use as an adjunctive therapy for chronic management of adult and pediatric patients greater than two months of age with Urea Cycle Disorders (UCDs).  A full summary of the opinion can be found here.  Detailed recommendations for the use of RAVICTI will be described in the summary of product characteristics (SmPC), which will be published in the European public assessment report (EPAR) and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission.

The adopted positive opinion will be considered by the European Commission for a binding decision to be issued for the granting of a centralized marketing authorization within 60 to 90 days from the date of adoption of the opinion.

RAVICTI was approved by the U.S. Food and Drug Administration (FDA) in February 2013 for chronic management of adult and pediatric patients greater than or equal to 2 years of age with UCDs who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. The European Centralized Marketing Authorization Application for RAVICTI included additional data to support an assessment of safety and efficacy in patients greater than two months of age.

"The adopted CHMP positive opinion marks an important step in bringing this medicine to those in the European Union and European Economic Area with Urea Cycle Disorders who are in need of additional treatment options," said Timothy P. Walbert, chairman, president and chief executive officer, Horizon Pharma plc. "If not managed appropriately, symptoms caused by high ammonia levels in the blood can significantly impact the body and brain. RAVICTI, pending a confirmatory binding decision by the European Commission, will cover a broader range of Urea Cycle Disorders compared to currently marketed medicines and will be easier for patients to use.

"The positive opinion represents a key milestone in our strategy to expand and build, organically and through acquisition, our infrastructure in Europe and the rest of the world. Based on our ability to rapidly execute and navigate the CHMP process since the Hyperion acquisition close, we have accelerated the timeline for our strategy in Europe," Walbert continued.

UCDs are inherited metabolic diseases caused by a deficiency of one of the enzymes or transporters necessary for the conversion of ammonia to urea, which results in heightened levels of ammonia in the bloodstream. 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 RAVICTI
RAVICTI is currently indicated for use in the United States as a nitrogen-binding agent for chronic management of adult and pediatric patients greater or equal to 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 and protein-free calorie supplements).

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 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 seven medicines through its orphan, primary care and specialty 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 timing of regulatory events related to potential marketing authorization for RAVICTI, the potential of RAVICTI to treat UCD patients and Horizon Pharma's strategy and plans to build its infrastructure in Europe and the rest of the world. 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 RAVICTI is ultimately approved for marketing in Europe, the fact that a positive CHMP opinion does not guarantee such approval, whether, if approved for marketing, Horizon Pharma will be able to obtain adequate pricing and reimbursement and successfully commercialize RAVICTI in Europe, whether Horizon Pharma will be able to successfully execute its growth strategy outside of the United States, 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.

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