Harliku is the only FDA-approved drug for alkaptonuria, a rare condition characterized by skin discoloration, arthritis and heightened risks of heart failure and stroke.
The FDA approved the use of Cycle Pharmaceuticals’ oral drug nitisinone on Thursday. The product will be marketed under the brand name Harliku, for use in adult patients with alkaptonuria.
Affecting one in 100,000 to 250,000 people worldwide, alkaptonuria (AKU) is an ultrarare genetic disease caused by a deficiency in the HGD an enzyme. Patients with AKU experience a pathological build-up of a particular acid in the skin, leading to ochronosis, or the bluish or reddish discoloration of patches of skin.
Aside from ochronosis, AKU can also affect the bones and joints, causing arthritis, poor mobility and a heightened risk of fractures. The disease can also impair lung function, lead to heart failure and increase the risk of coronary artery disease and stroke.
A small-molecule drug, Harliku works by blocking a key enzyme in the HGD cascade, ultimately reducing urine HGA levels. Cycle aims to launch Harliku, which is the first FDA-approved AKU treatment in the U.S., by July. The drug does not come with a boxed warning but carries precautions for lowered white blood and platelet counts, ocular symptoms and hyperkeratotic plaques, an abnormal thickening of the skin.
Supporting Harliku’s approval are data from a 40-patient randomized clinical trial, which showed that the drug improved pain, physical function and energy after three years of treatment, Cycle said in Thursday’s release.
The trial was published in October 2024 in Molecular Genetics and Metabolism. “The findings of this study suggest that the clinical impact of nitisinone aligns with its biochemical reduction of HGA, pointing to nitisinone as a therapy for alkaptonuria,” the researchers wrote at the time.
Harliku’s approval comes as the rare disease space appears poised for newfound tailwinds, with health authorities voicing support for regulatory flexibility. In April, FDA Commissioner Marty Makary said his office is considering a “new pathway” for rare disease therapies, opening up approvals based on a “plausible mechanism.”
Health Secretary Robert F. Kennedy Jr. has also agreed with this push, saying earlier this month that “we are going to continue to figure out new ways . . . of accelerating approvals for drugs and treatments that treat rare diseases.”
