PTC923 for Hyperphenylalaninemia Granted Orphan Drug Status

In late May 2021, biopharmaceutical company PTC Therapeutics, Inc. (“PTC”) shared that its therapy, PTC923, received Orphan Drug designation within both the United States and Europe. The treatment is designed for patients with hyperphenylalaninemia, of which phenylketonuria (PKU) makes up a majority of diagnoses (98%).


Although there are some available ways to manage a PKU diagnosis, such as PKU formula and a special diet, there is a specific need to provide additional, accessible, and effective treatment options for patients. PTC hopes to fill this unmet need through PTC923.

PTC is an orally administered synthetic sepiapterin formulation. This synthetic sepiapetrin is an intracellular tetrahydrobiopterin precursor. Normally, intracellular tetrahydrobiopterin plays a role in nitric oxide synthase activity, metabolic processes, and metabolic product synthesis. Researchers aim to begin the Phase 3 APHENITY clinical trial relatively soon.

So what does receiving Orphan Drug status mean? In the United States, Orphan Drug designation is granted to drugs or biologics designed to treat “rare” or life-threatening conditions. Within the United States, a rare condition affects 200,000 people or less. Once a drug developer is granted this status, they receive additional assistance from the FDA, such as fee waivers, tax credits, FDA regulatory assistance, and 7 years of market exclusivity (once the drug is approved).

In Europe, Orphan Drug designation (Orphan Medicinal Product) is granted to life-threatening, rare, or chronically debilitating conditions affecting no more than 5 in every 10,000 people. Once granted, drug developers receive fee reductions, protocol assistance, and 10 years of market exclusivity (if the product maintains Orphan Drug status during marketing authorization).


Generally, PAH gene mutations cause hyperphenylalaninemia, a rare genetic condition and inborn error of metabolism in which excess phenylalanine, an essential amino acid, accumulates in the blood. QDPR, PTS, PCBD1, and GCH1 gene mutations have also been associated with this condition. Because hyperphenylalaninemia is inherited in an autosomal recessive pattern, patients must receive one defective copy from each parent. These genetic mutations prevent the body from properly metabolizing phenylalanine. Since nerve cells in the brain are sensitive to phenylalanine, too much can cause a host of health issues. However, most patients have normal lifespans.

An estimated 98% of diagnoses are phenylketonuria (PKU), which manifests as phenylalanine levels over 20 mg/dL. Symptoms of PKU, which typically appear in the first few months of life, include:

  • Musty-smelling breath, urine, or skin
  • Poor melanin production, resulting in fair skin and eyes
  • Developmental and intellectual delays
  • Seizures
  • Hyperactivity
  • Lowered bone strength
  • Microcephaly
  • Eczema and other skin rashes
  • Heart defects

Learn more about hyperphenylalaninemia.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

Follow us