Regulatory Milestone and Disease Background

The U.S. FDA has approved nitisinone (HARLIKU) for reducing urine homogentisic acid in adults with alkaptonuria (AKU), a rare, progressive metabolic disorder that can cause severe arthritis, heart disease, and pigmentary changes. Prior to this approval, there were no FDA-authorized therapies for AKU, leaving patients and clinicians reliant on symptomatic management and supportive care.

Cycle Pharmaceuticals CEO, Dr. Antonio Benedetti, said in a press statement: “This is a defining moment for everyone touched by alkaptonuria. To deliver a solution where none existed before is the highest calling of drug innovation.”

Scientific Evidence and Mechanistic Insights

Nitisinone blocks the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD), preventing the formation of homogentisic acid—a metabolite that accumulates in AKU and causes tissue damage. Approval was based on results from multicenter Phase 3 clinical trials, where nitisinone reduced urinary homogentisic acid levels by up to 99%, stabilized disease progression, and improved musculoskeletal outcomes. Most adverse events were mild elevations in tyrosine levels, managed by dietary intervention.

Dr. Benedetti added: “HARLIKU shows that targeted enzyme blockade can fundamentally alter the course of rare metabolic disease and may catalyze similar advances in other neglected conditions.”

Industry and Research Impact

The FDA’s decision has broader implications for the rare disease landscape; HARLIKU is expected to pave the way for additional therapies in metabolic genetics. Cycle Pharmaceuticals highlighted ongoing post-marketing surveillance and collaborations with genetic medicine consortia for long-term outcome studies.

International Collaboration and Patient Advocacy

Patient groups and clinical researchers from North America and Europe were integral to HARLIKU’s development, contributing to registry data and natural history studies. Dr. Benedetti credited these partnerships for “bringing the AKU community’s voice and suffering to the heart of drug development.”

Looking Ahead

Cycle anticipates a Q3 launch for HARLIKU in the U.S. and EU, with expanded access programs in Asia-Pacific underway.