Chicago, Illinois, USA, September 8, 2026
Orphalan has initiated the global Phase 3 TRADITiONAL clinical trial evaluating an investigational once-daily formulation of trientine tetrahydrochloride as a potential first-line treatment for Wilson disease, a rare inherited disorder of copper metabolism. The randomized study will compare the investigational formulation with D-penicillamine (DPA), an established copper-chelating therapy, over 48 weeks. The program aims to determine whether a simplified once-daily treatment approach can provide an effective and well-tolerated option for patients who require lifelong management of Wilson disease.
Global Phase 3 Study Targets First-Line Wilson Disease
The TRADITiONAL Study is a global, multicenter, randomized, parallel-group, open-label Phase 3 trial enrolling symptomatic and asymptomatic patients aged 8 years and older with Wilson disease. Participants can be treatment-naïve or naïve to chelator therapy, with certain symptomatic patients who have received zinc salts for a limited period also eligible. Following approximately four weeks of screening, participants will receive 48 weeks of treatment with either the investigational once-daily trientine formulation or D-penicillamine. The study will evaluate efficacy, safety, tolerability and patient-reported treatment satisfaction, providing a broad assessment of the potential new formulation. U.S. sites include the University of Colorado Anschutz School of Medicine, Yale University School of Medicine and the University of Michigan Medical Center, with additional sites expected as enrollment expands internationally to China, Pakistan and Saudi Arabia. The clinical program is designed around an important treatment challenge in Wilson disease: patients require lifelong therapy to control toxic copper accumulation. Current treatment regimens can be complex and may create adherence challenges, making dosing convenience an important consideration in long-term disease management.
Once-Daily Trientine Could Reduce Treatment Burden
Wilson disease is caused by mutations in the ATP7B gene, which impair the body’s ability to eliminate excess copper. Copper can subsequently accumulate in organs including the liver and brain, potentially causing serious hepatic, neurological and psychiatric complications. Without appropriate lifelong treatment, Wilson disease can be life-threatening. Trientine is a copper-chelating agent that helps remove excess copper from the body. Orphalan’s investigational formulation is being evaluated with the goal of providing treatment through a once-daily dosing regimen, potentially simplifying therapy compared with more frequent dosing schedules. The Phase 3 comparison against D-penicillamine is clinically relevant because DPA is an established copper-chelating treatment used in Wilson disease. The study will therefore assess whether the investigational formulation can demonstrate an appropriate balance of clinical efficacy, safety, tolerability and treatment satisfaction in patients beginning long-term therapy. Importantly, the new Phase 3 program is investigating a new dosing formulation and first-line treatment strategy. It should not be interpreted as evidence that once-daily trientine has already demonstrated superiority over existing therapy.
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Trial Builds on Orphalan’s Wilson Disease Portfolio
Orphalan is already focused on rare-disease treatments, including therapies for Wilson disease, and the TRADITiONAL program represents a further step in expanding treatment options for the condition. The company currently markets Cuvrior (trientine tetrahydrochloride) in certain Wilson disease populations, while the once-daily formulation being tested in TRADITiONAL remains investigational. The FDA lists Cuvrior as approved for adults with stable Wilson disease who are de-coppered and tolerant to penicillamine, underscoring that the new first-line Phase 3 program addresses a different treatment setting. The broader development effort also has regulatory recognition in Europe, where trientine tetrahydrochloride received orphan designation for Wilson disease in May 2026 for the investigational development program. Orphan designation provides regulatory support but does not constitute marketing authorization or approval. The initiation of TRADITiONAL therefore marks a significant clinical-development milestone for Orphalan and its Wilson disease portfolio. If the investigational once-daily formulation demonstrates favorable efficacy and safety in the Phase 3 program, it could potentially offer patients a more convenient long-term treatment approach while addressing an important unmet need in rare-disease care.
Source: Orphalan press release
