Once-Daily Trientine Tetrahydrochloride Aids Adherence in Wilson Disease

Switching to a once-daily trientine tetrahydrochloride formulation (QD TETA4) improved self-reported treatment convenience and medication adherence in adults with Wilson disease, according to findings from a phase 2 decentralized switch study presented at AASLD The Liver Meeting 2026.^1,2

Emmanuel Tsochatzis, MD, PhD, of the Royal Free Hospital and University College London, presented 2 analyses from the trial, one focused on patient interviews and one on study feasibility and patient-reported outcomes (PROs).

Suboptimal adherence to lifelong maintenance therapy is increasingly recognized in Wilson disease, and all participants entered the study on chelator, zinc, or combination regimens prescribed at least twice daily.² No Wilson disease-specific treatment satisfaction PRO exists, and the investigators aimed to capture the patient experience directly through interviews and validated questionnaires.¹

How Did Once-Daily TETA4 Affect Convenience and Adherence?

The phase 2 study enrolled adults with Wilson disease (Leipzig score ≥4) on maintenance therapy prescribed at least twice daily. Participants switched from SoC to QD TETA4 for 28 days, followed by a return to SoC for 28 days. Chelator doses converted mg-for-mg, rounded to the nearest full tablet, while zinc-treated patients converted to 600 mg (2 tablets).²

A total of 10 participants (7 male; mean age, 35.3 years [range, 21-55]) enrolled, with hepatic (n = 2), neurologic (n = 3), mixed (n = 3), and asymptomatic (n = 2) phenotypes.² Baseline SoC included trientine (n = 4), zinc (n = 3), D-penicillamine (n = 2), and combination trientine and zinc (n = 1).

The Treatment Satisfaction Questionnaire for Medication (TSQM-9) convenience score rose from a mean of 43.1 (90% CI, 26.3-59.9) at baseline to 85.0 (90% CI, 78.4-91.6) after 28 days of QD TETA4 (P = .008), then fell to 40.7 (90% CI, 26.9-54.4) after the return to SoC. Adherence followed the same pattern, with Morisky Medication Adherence Scale (MMAS-8) scores of 4.8 (90% CI, 3.7-5.8), 7.7 (90% CI, 7.4-8.0; P = .002), and 5.0 (90% CI, 4.0-5.9) at the same timepoints. Scores below 6 indicate poor adherence, and TSQM-9 effectiveness did not change, while satisfaction improved without reaching significance.^1,2

What Did Patients With Wilson Disease Say About Once-Daily Dosing?

In semi-structured online interviews conducted by PRO development experts, treatment satisfaction with QD TETA4 was high. A total of 5 participants rated their satisfaction as “very much” and 3 as “quite a bit.”¹

Of the 80% of participants preferring QD TETA4, the most cited benefits over SoC were dosing schedule (n = 5), reduced mental load (n = 3), fewer adaptations and less planning (n = 2), and side effects (n = 2).¹ Among participants asked, 78% (7/9) rated once-daily dosing as “much less challenging” for adherence and “much less disruptive” to daily life. No participant reported a worsening treatment experience.¹

Nine adverse events, 8 mild and 1 moderate, occurred in 7 participants, and all resolved.² The investigators concluded QD TETA4 meaningfully reduced treatment burden through dosing simplification, reduced mental load, and fewer planning demands.¹

Can Decentralized Trials Work in Rare Liver Disease?

The second analysis evaluated the decentralized design itself. Six UK centers of excellence referred participants from London, Birmingham, and Leeds to a virtual clinical trial center, with a single centralized ethics committee approval. Medications were dispensed and returned through a remote pharmacy, and blood draws, investigator visits, PRO questionnaires, and interviews took place in participants’ homes.²

Paper PRO questionnaires were mailed to participants and collected by courier on 5 fixed dates. The cohort represented more than 4 ethnic groups, and all PROs were fully completed. The authors concluded the findings confirm the feasibility of a decentralized trial in rare liver disease, with nationwide enrollment, diverse phenotypes, and successful home blood collection with central laboratory analysis.²

According to the investigators, decentralized designs may reduce participant burden and improve trial efficiency and access, which are important considerations for rare disease research.² The FDA also encourages inclusion of the patient voice in medical product development.¹

References

1. Tsochatzis E, Kamlin CO, Hurt C, et al. Understanding the drivers of treatment experience and adherence in Wilson disease: what do patient interviews and reported outcomes from a phase 2 study evaluating a new trientine tetrahydrochloride formulation tell us? Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.

2. Tsochatzis E, Ala A, Holt A, et al. De-centralized clinical trials in rare disease: incorporating the patient voice in the evaluation of tolerability, treatment satisfaction and adherence of a novel trientine tetrahydrochloride formulation for the treatment of Wilson disease. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.