The FDA approved nitisinone (Harliku) for the reduction of urine homogentisic acid (HGA) in adults with alkaptonuria, Cycle Pharmaceuticals announced on Thursday.
Alkaptonuria is an ultra-rare hereditary disorder of tyrosine and phenylalanine catabolism, and is commonly known as black urine disease due to the noticeable buildup of HGA. A slow-progressing disease, alkaptonuria can cause tissue damage, pain, and reduced joint mobility; it has been linked to cardiac valvular disease and genitourinary stones, though presentation is variable.
Cycle said the approval was based on a small randomized trial showing that 3 years of nitisinone resulted in improvements in pain, energy levels, and physical functioning among patients with alkaptonuria. This focus on patient-reported outcomes arose after an older study had failed to prove that nitisinone had a hip motion benefit or improved musculoskeletal function among affected individuals.
“The approval of Harliku is an important advance for the AKU [alkaptonuria] community,” said Wendy Introne, MD, of the National Human Genome Research Institute, who was an author for both studies, in a statement. “We stand hopeful that it can ease the significant burden of AKU.”
The hydroxyphenylpyruvate dioxygenase inhibitor should be taken orally at a recommended dosage of 2 mg once daily, according to its label.
Warnings about nitisinone use include concerns about elevated plasma tyrosine levels, which may in turn cause ocular symptoms and hyperkeratotic plaques. Providers are advised to assess plasma tyrosine levels in patients presenting with ocular signs and symptoms and restrict diet as necessary.
There have also been reports of leukopenia and severe thrombocytopenia while on nitisinone, leading to an FDA advisory to have platelet and white blood cell counts monitored during therapy.
Nitisinone’s maker said the product will hit shelves next month.
The drug is also available as a generic and was previously approved under the name Nityr for hereditary tyrosinemia type 1 in combination with dietary restriction of tyrosine and phenylalanine.
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