FDA Approves Nitisinone (HARLIKU) for Treatment of Alkaptonuria

The US Food and Drug Administration (FDA) has approved nitisinone (HARLIKU) for the reduction of urine homogentisic acid (HGA) in adults with alkaptonuria (AKU).1

Announced by parent company Cycle Pharmaceuticals on June 19, 2025, this approval makes nitisinone the first and only FDA-approved treatment for AKU. A launch is planned for July 2025.1

A rare genetic disease with no known cure, AKU affects roughly 1 in 100,000 to 250,000 worldwide. The disease causes patients to experience a buildup of HGA, which results in osteoarthritis, ochronosis, and complications in the heart and kidneys. Additionally, patients often develop pain and reduced joint mobility, requiring large joint replacements.1,5

“The approval of HARLIKU is an important advance for the AKU community,” said Wendy Introne, MD, biochemical geneticist at National Human Genome Research Institute, National Institutes of Health. “Our scientific team has translated decades of research into launching nitisinone as a new treatment option, and we stand hopeful that it can ease the significant burden of AKU.”1

The approval is based on the results of a post-hoc analysis of a trial conducted in 2009. This study enrolled 40 patients with AKU and randomized them evenly to treatment and control arms. The former received nitisinone 2 mg orally, once daily, while the latter received no treatment. The study demonstrated the efficacy and safety of nitisinone for treating AKU; however, although the treatment arm exhibited positive results in range of motion changes compared to control, these were not clinically significant, and the study failed to reach its primary endpoint.2

The later post-hoc analysis examined patient-reported outcomes, noting improvements over 3 years in the 36-Item Short-Form Survey and 6-minute walk test. These later results, coupled with the initial trial’s proof of efficacy, suggested that nitisinone improves both quality of life and function in patients with AKU.3

“We are deeply grateful for Cycle’s collaboration with Dr. Wendy Introne, Dr. Bill Gahl, and the broader team at the NIH, whose pioneering work laid the foundation for this FDA approval,” said Steve Fuller, Chief Strategy Officer at Cycle Pharmaceuticals. “We look forward to making HARLIKU available to U.S. AKU patients as soon as possible and remain committed to supporting the AKU community to the fullest extent of our capabilities.”1

In 2017, Cycle Pharmaceuticals received approval for Nityr, a similar nitisinone-based drug to treat Hereditary Tyrosinemia Type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine. The drug did not require inflammation and could be dissolved in water for pediatric patients. Like AKU, HT-1 is an ultra-rare genetic disease which causes hepatic, renal, and peripheral nerve damage.4

References

1. Cycle Pharmaceuticals. Cycle Pharmaceuticals’ HARLIKU (nitisinone) Tablets Receive First FDA-Approval as Treatment for Alkaptonuria (AKU). BusinessWire. June 19, 2025. Accessed June 20, 2025. https://www.businesswire.com/news/home/20250611798305/en/Cycle-Pharmaceuticals-HARLIKU-nitisinone-Tablets-Receive-First-FDA-Approval-as-Treatment-for-Alkaptonuria-AKU

2. Gahl W. Long-Term Study of Nitisinone to Treat Alkaptonuria. ClinicalTrials.gov identifier: NCT00107783. Updated August 26, 2021. Accessed June 20, 2025. https://clinicaltrials.gov/study/NCT00107783?tab=results

3. Spears KR, Rossignol F, Perry MB, et al. Patient-reported outcomes and functional assessments of patients with Alkaptonuria in a 3-year Nitisinone treatment trial. Mol Genet Metab. 2024;143(1-2):108562. doi:10.1016/j.ymgme.2024.108562

4. Cycle Pharmaceuticals. Cycle Pharmaceuticals Receives FDA Approval of Nityr (nitisinone) Tablets for Treatment of HT-1. August 1, 2017. Accessed June 20, 2025. https://cyclepharma.com/news/cycle-pharmaceuticals-receives-fda-approval-of-nityrtm-nitisinone-tablets-for-treatment-of-ht-1/

5. Zatkova A. An update on molecular genetics of Alkaptonuria (AKU). J Inherit Metab Dis. 2011;34(6):1127-1136. doi:10.1007/s10545-011-9363-z