FDA Approves Age-Range Expansion on One of World's Most Expensive Drugs

The US Food and Drug Administration (FDA) has approved Horizon Pharma’s supplemental New Drug Application (sNDA) to expand the age range of glycerol phenylbutyrate (RAVICTI Oral Liquid/Horizon Pharma Plc.) to people 2 months of age and older with urea cycle disorders (USDs) that cannot be managed by dietary protein restrictions and/or amino acid supplementation alone.

Glycerol phenylbutyrate was first approved in the US in February 2013 for the chronic management of adult and pediatric patients 2 years of age and older. It ranks among the world’s most expensive prescription drugs, with an annual cost estimate of $556,000 per patient per year, according to Matt Flesch, executive director of product communications at Horizon.

“This approval represents a significant advance for very young children with UCDs, one of the most vulnerable patient populations, as more severe cases of the disease tend to present earlier in life and can lead to serious long-term impairments if not diagnosed and treated early,” said Susan Berry, MD, professor and division director for genetics and metabolism, department of pediatrics, University of Minnesota and primary investigator for the glycerol phenylbutyrate studies leading to the sNDA approval.

The most recent approval is based on 3 studies that assessed monthly ammonia control and hyperammonemic crises (HACs) in pediatric patients with UCDs 2 months to 2 years of age. In these studies, patients were treated with glycerol phenylbutyrate for an average of 8 months, and received glycerol phenylbutyrate either at study initiation or by enrolling on stable doses of sodium phenylbutyrate or sodium benzoate then switching to equivalent doses of glycerol phenylbutyrate. Results found glycerol phenylbutyrate to be to be safe and effective in the pediatric patients studied, with glycerol phenylbutyrate-treated patients maintaining stable ammonia levels relative to their pre-study enrollment.

“Through our ongoing collaboration with physicians and parents of children living with UCDs, we understand the devastating effects of hyperammonemic events early in a child’s life,” said Jeffrey W. Sherman, MC, FACP, executive vice president, research and development and chief medical officer, Horizon Pharma Plc. “The approval by the FDA of our sNDA to expand RAVICTI to children as young as two months is an important step in helping young children with UCDs. We will continue to invest in RAVICTI to address the unmet needs of those with UCDs, as well as help their caregivers and family members more confidently tackle the challenges of the disease.”

Adverse reactions to glycerol phenylbutyrate include diarrhea, flatulence, headache, nausea, vomiting, decreased appetite, dizziness, headache, fatigue, upper abdominal pain, rash, neutropenia, pyrexia, hypophagia, cough, nasal congestion and rhinorrhea.

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.