DUBLIN, IRELAND–(Marketwired – Jun 29, 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 it has submitted a supplemental New Drug Application (sNDA) with the U.S. Food and Drug Administration (FDA) for RAVICTI® (glycerol phenylbutyrate) Oral Liquid to expand the age range for chronic management of urea cycle disorders (UCDs) in adult and pediatric patients from two years of age to two months of age and older.

RAVICTI is currently indicated for use as a nitrogen-binding agent for chronic management of adult and pediatric patients greater than two years of age with UCDs who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. The sNDA seeks to expand the approved age range for RAVICTI to include children as young as two months of age, and is based on a clinical development program including two clinical trials that enrolled 17 UCD patients between the ages of two months and two years.

“This sNDA is an important milestone in the RAVICTI development program, and is consistent with our approach to reinvest in our medicines as we prioritize research to meet the unmet needs of people with devastating diseases,” said Jeffrey W. Sherman, M.D., FACP, executive vice president, research and development and chief medical officer, Horizon Pharma plc. “Through our work with healthcare professionals and the UCD community, including patients and their families, we’ve learned that UCDs often strike early in a child’s life and can be extremely challenging to manage, if not life threatening. In response, several studies were conducted evaluating the efficacy and safety of RAVICTI in very young children. We will now work with the FDA to determine whether the age range for RAVICTI can be expanded to include patients as young as two months of age.”

In addition, Horizon recently partnered with Clinigen Group’s Idis Managed Access (MA) division to initiate a Managed Access Program (MAP) in select European countries for eligible, individual patients living with UCDs. RAVICTI was approved in Europe in November 2015. 

“Where local health authorities permit, the MAP will allow healthcare professionals access to RAVICTI while Horizon works through its country-by-country plan to make RAVICTI commercially available in Europe,” continued Dr. Sherman. 

Healthcare Professionals can obtain details about the RAVICTI Managed Access program by calling  +44 (0) 1932 824 123, or emailing [email protected].

About Urea Cycle Disorders (UCDs)
UCDs are rare, 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 RAVICTI
In the U.S., RAVICTI was approved in February 2013 and is indicated for use as a nitrogen-binding agent for chronic management of adult and pediatric patients ≥ 2 years of age with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. RAVICTI in the U.S. must be used with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, 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

Visit www.RAVICTI.com to download a copy of the RAVICTI Full Prescribing Information.

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, rheumatology and primary care 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.

About Clinigen Group
Clinigen Clinical Trial Services is the global market leader in the management and supply of commercial medicines for clinical trials.

The Group is also the trusted global leader in ethically sourcing and supplying unlicensed medicines to hospital pharmacists and physicians for patients with a high unmet need, through three of its divisions: Idis Managed Access runs early access programs for innovative new medicines. Idis Global Access and Link Healthcare work directly with healthcare professionals to enable compliant access to unlicensed medicines on a global basis and niche essential licensed and generic medicines across Australasia, Africa and Asia (AAA region).

Clinigen Specialty Pharmaceuticals acquires global rights, revitalises and markets its own portfolio of niche hospital commercial products.

For more information, please visit www.clinigengroup.com

Forward-Looking Statements
This press release contains forward-looking statements, including statements regarding the potential of RAVICTI to treat UCD patients, the potential to expand RAVICTI’s approved indication to include patients as young as two months of age, the expected impact of the MAP for RAVICTI access in Europe and Horizon Pharma’s strategy and plans to commercialize RAVICTI in Europe. 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 Horizon Pharma’s sNDA will be approved, whether Horizon Pharma will be able to obtain adequate pricing and reimbursement and successfully commercialize RAVICTI in Europe or elsewhere outside of the United States, whether physicians outside of the United States will prescribe RAVICTI, whether RAVICTI will be sufficiently available in Europe through the MAP or otherwise, whether Horizon Pharma is able to maintain regulatory data and market protections and orphan exclusivity for RAVICTI in Europe, 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.