FDA Approves Cycle Pharmaceuticals' HARLIKU™ for Alkaptonuria (AKU)

Cycle Pharmaceuticals has announced that the U.S. Food and Drug Administration (FDA) has given approval for HARLIKU (nitisinone) Tablets, intended to lower urine homogentisic acid (HGA) in adults diagnosed with alkaptonuria (AKU). The medication, set to launch in July 2025, represents a significant milestone as the first and only FDA-approved treatment for AKU, a rare genetic metabolic disorder. This condition is characterized by an accumulation of HGA, which can result in severe complications such as osteoarthritis, ochronosis, and issues affecting the kidneys and heart. Individuals with AKU often experience substantial pain, decreased joint mobility, and may necessitate joint replacements, significantly impacting their physical abilities, emotional health, and overall quality of life.

The approval of HARLIKU is founded on findings from a randomized, no-treatment controlled trial involving 40 AKU patients. Conducted under the National Human Genome Research Institute's program at the National Institutes of Health (NIH), Dr. Wendy J. Introne and her team demonstrated that nitisinone yielded improvements in pain management, energy levels, and physical functioning after three years of therapy, as measured by the 36-Item Short-Form Survey.

Steve Fuller, Chief Strategy Officer of Cycle Pharmaceuticals, expressed gratitude for the collaboration with Dr. Wendy Introne, Dr. Bill Gahl, and the NIH team, acknowledging their crucial role in achieving FDA approval. Fuller emphasized the company’s eagerness to make HARLIKU available to AKU patients in the U.S. promptly, reinforcing their commitment to supporting the AKU community to the fullest extent possible.

Dr. Wendy J. Introne from the NIH National Human Genome Research Institute hailed HARLIKU’s approval as a significant advancement for individuals living with AKU. She noted that the scientific team has successfully translated extensive research into a new treatment option, bringing hope that HARLIKU can alleviate the substantial burdens associated with AKU.

Building on Cycle Pharmaceuticals' previous achievements in rare disease treatments, HARLIKU will be their eighth commercial product available in the United States.

HARLIKU is specifically indicated for reducing urine homogentisic acid levels in adults with AKU. However, there are important safety considerations to be aware of when prescribing this medication. Patients allergic to nitisinone or any components of HARLIKU should not receive the prescription. Regular slit-lamp examinations are recommended to monitor ocular symptoms linked to elevated plasma tyrosine levels, such as keratitis and corneal irritation, and assessments of plasma tyrosine concentrations should be conducted if any abrupt neurological changes occur.

Additionally, patients undergoing HARLIKU therapy require monitoring of platelet and white blood cell counts due to potential reversible leukopenia and thrombocytopenia observed in clinical trials involving hereditary tyrosinemia type 1 patients. Common adverse reactions reported include elevated tyrosine levels, thrombocytopenia, and keratitis.

Those administering HARLIKU must be cautious of drug interactions, as nitisinone can moderately inhibit CYP2C9 and weakly induce CYP2E1. Adjustments to dosages of co-administered drugs metabolized by CYP2C9 may be necessary, along with monitoring for adverse effects when used alongside OAT1/OAT3 substrates.

Regarding specific populations, there is limited data on the drug’s effects during pregnancy, and its safety and efficacy have not been established in pediatric or geriatric AKU patients. Caution is advised for elderly patients due to potentially reduced hepatic, renal, or cardiac function, as well as other drug therapies.

Cycle Pharmaceuticals continues to focus on providing treatments and product support for rare diseases, with headquarters in Cambridge, UK, and offices in Boston, Massachusetts, U.S.