ROCKVILLE, MarylandThe US Food and Drug Administration (FDA) has approved
the orphan drug Orfadin (nitisinone capsules, Swedish Orphan International) for
treating hereditary tyrosinemia type 1 (HT-1), a rare pediatric disease that
causes progressive liver failure and liver cancer. In announcing its approval
decision, the agency warned that only physicians experienced in treating the
disease should prescribe Orfadin. Rare Diseases Therapeutics, Inc., of
Nashville, Tennessee, is the drug’s US distributor.
HT-1 results from the inhibition of an enzyme involved in an early step in
the tyrosine catabolic pathway. The disorder is present at birth and manifests
itself within weeks or months in the failure of the infant to thrive and by
symptoms of hepatomegaly, edema, ascites, melena, and hemorrhagic diathesis.
HT-1 is fatal in the first year of life without therapy, and treated
patients rarely live into their 20s without a liver transplant. Fewer than 100
children in the United States have the disease.
The agency acted after reviewing a study of more than 180 patients (median
age, 9 months) treated with Orfadin and a diet that restricted intake of the
amino acids tyrosine and phenylalanine. In that trial, children less than 2
months old at the time of diagnosis had a 4-year survival rate of 88%.
Historical data on children treated with dietary restrictions alone puts the
4-year survival rate at 29%.
The most common side effects were related to high tyrosine levels due to
failure of the children to eat the appropriate diet. Excessive levels of that
amino acid can be toxic to the eyes, skin, and nervous system. Researchers also
reported rare instances of mild reductions in platelet and white blood cell