FDA Approves Cycle Pharmaceuticals’ Harliku for Alkaptonuria

Author(s):

Harliku becomes the first FDA-approved treatment for alkaptonuria, indicated to reduce homogentisic acid levels in affected adults.

Medical concept about Alkaptonuria with inscription on the sheet.

Image Credit: Adobe Stock Images/Yurii Kibalnik

Key Takeaways

First FDA-approved treatment for alkaptonuria (AKU): Harliku (nitisinone) becomes the first therapy authorized by the FDA to treat alkaptonuria, an ultra-rare genetic metabolic disorder.
Demonstrated biochemical efficacy: In a three-year NIH-led study, Harliku reduced urinary and plasma homogentisic acid (HGA) levels by more than 95%.
Expected US launch in July 2025: Cycle Pharmaceuticals plans to make Harliku available to patients with AKU next month following FDA approval.

The FDA has approved Cycle Pharmaceuticals’ Harliku (nitisinone), marking the first authorized treatment for alkaptonuria (AKU), an ultra-rare genetic metabolic disorder. According to the company, approval was based on a Phase II interventional study conducted at the National Institutes of Health’s National Human Genome Research Institute (NHGRI), which demonstrated that long-term use of Harliku improved patients’ pain, energy, and physical functioning.^1,2

What Does FDA Approval of Harliku Mean for Patients with AKU?

"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, Cycle Pharmaceuticals, in a press release. “We look forward to making HARLIKU available to US AKU patients as soon as possible and remain committed to supporting the AKU community to the fullest extent of our capabilities."

Phase II Study Design and Endpoints

The randomized, no-treatment controlled study evaluated the long-term safety and efficacy of Harliku in 40 patients between 30 and 80 years of age with AKU and at least one functioning hip.
During the three-year trial, patients were randomly assigned to receive either daily 2 mg of Harliku alongside standard care or standard care alone.
All patients returned every four months for follow-up testing, with more extensive assessments each year. After 16 months, efficacy was assessed.
The primary endpoint of the trial was change in baseline in the total hip range of motion in the worse hip at three years. Key secondary endpoints included change from baseline in Schober’s test, change from baseline of functional reach assessment, change form baseline of timed get up and go, and change from baseline in six-minute walk.²

Efficacy Outcomes

Results show that Harliku significantly reduced homogentisic acid (HGA), the disease-causing metabolite in AKU.
Urinary HGA excretion dropped by over 95% from a mean of 5.1 grams/day to approximately 125 mg/day within four months and remained stable throughout the trial.
Additionally, Plasma HGA also declined by 95%.
The change in range of motion in the worse hip showed only a minor, non-significant benefit in the treatment group, with a two-degree improvement per year.
The secondary endpoints similarly did not achieve significant improvements with treatment.

Safety Profile

In terms of safety, seven patients discontinued treatment due to adverse events (AEs), including one death from myocardial infarction, corneal opacities, and liver enzyme elevations.
The most common AEs associated with Harliku include elevated tyrosine levels, thrombocytopenia, and keratitis. Additionally, there were eight serious AEs reported during the trial.
However, no new safety signals were identified outside of the treatment’s known risks.³

Rare Disease Context and Market Outlook

According to Medline Plus, AKU affects between one in 250,000 and one in one million people in the United States. It is most common in certain regions of Slovakia, with an incidence of one in 19,000, as well as in the Dominican Republic.⁴

“The approval of Harliku is an important advance for the AKU community,” said Wendy J. Introne, MD, NHGRI, in the press release. “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.”

According to Cycle, Harliku is expected to launch in July.¹

References

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

2. Long-Term Study of Nitisinone to Treat Alkaptonuria. Clinicaltrials.gov. Accessed June 19, 2025. https://clinicaltrials.gov/study/NCT00107783

3. A 3-year Randomized Therapeutic Trial of Nitisinone in Alkaptonuria. PubMed. Accessed June 19, 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC3148330/?utm_source=chatgpt.com

Alkaptonuria. Medline Plus. Accessed June 19, 2025. https://medlineplus.gov/genetics/condition/alkaptonuria/

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