FDA

Harliku (nitisinone) approved for alkaptonuria

June 26, 2025

Brand name: Harliku

Generic name: nitisinone

Manufacturer: Cycle Pharmaceuticals

Approval date: June 19, 2025

FDA approved Harliku (nitisinone) tablets for the reduction of urine homogentisic acid (HGA) in adult patients with alkaptonuria (AKU).

According to a manufacturer press release, AKU is an ultra-rare genetic metabolic disorder resulting in a buildup of HGA that leads to osteoarthritis, ochronosis, as well as cardiac and renal complications. Affected patients often develop pain, reduced joint mobility, and require large joint replacements.

Nitisinone is a competitive inhibitor of hydroxyphenyl-pyruvate dioxygenase, an enzyme upstream of homogentisate 1,2-dioxygenase (HGD) in the tyrosine catabolic pathway.

Efficacy

Approval was based on results from an open-label, single center, randomized, no-treatment controlled trial in 40 adults diagnosed with AKU (NCT00107783). Patients received either Harliku 2 mg PO once daily or no treatment for three years.

The Harliku group had an average percent reduction from baseline in urinary HGA of 88% (95% confidence interval [CI], 79-97%) after 1 year of treatment and a 91% reduction from baseline at year 3 (95% CI, 85-97%). In contrast, untreated controls had an average increase of 107% from baseline to year 1 (95% CI, 0-216%) and 108% from baseline to year 3 (95% CI, 19-198%).

Safety

The most common adverse reactions (>1%) in the trial were elevated tyrosine levels, keratitis, and thrombocytopenia.

Recommended dose

The recommended dosage of Harliku is 2 mg PO once daily.

Sources:

Harliku (nitisinone) [package insert]. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209449s018lbl.pdf Revised June 2025. Accessed June 25, 2025.

Cycle Pharmaceuticals’ Harliku™ (nitisinone) tablets receive first FDA-approval as treatment for alkaptonuria (AKU). [News release]. 2025. https://cyclepharma.com/news/first-fda-approved-treatment-for-aku/