Once-Daily Trientine Matches Twice-Daily Exposure in Wilson Disease

A novel once-daily formulation of trientine tetrahydrochloride (TETA 4HCl) achieved systemic drug exposure comparable to the approved twice-daily formulation, according to phase 1 TRIUMPH-3 data presented by Michael Schilsky, MD, at The Liver Meeting 2026 in Denver, Colorado.

The findings target a persistent challenge in Wilson disease: lifelong therapy that depends on adherence. Current anticopper drugs require at least twice-daily dosing timed away from meals, and missed doses often cause no immediate symptoms, Schilsky, professor of medicine at Yale School of Medicine, told HCPLive.

“Any time you increase beyond once a day, the amount of non-adherence, non-compliance goes up very dramatically,” he said.

What Did TRIUMPH-3 Show?

In the randomized, open-label, crossover study, 26 participants received a total daily dose of 900 mg trientine base, either as a new 300-mg formulation once daily or as the EU-approved 150-mg formulation in 2 divided doses 8 hours apart. Peak plasma concentration roughly doubled with once-daily dosing (geometric mean, 3436 vs 1567 ng/mL), but total exposure was comparable, with a geometric mean ratio of 1.155 for AUC0-24. Concentrations at 48 hours were also similar, suggesting excretion is independent of dosing frequency. Five participants experienced 8 adverse events, 7 of them mild.1

Schilsky notes that the formulation itself was the key hurdle. His group’s 2015 pilot study found once-daily trientine effective in 8 patients with stable disease, but existing tablets created a high pill burden.2 The new formulation fits double the drug into nearly the same tablet size.

What Comes Next?

Because once-daily dosing produces a higher peak, studies must still show that the greater initial exposure is well tolerated by the liver. Separate patient-reported data presented at the meeting suggest once-daily dosing may improve convenience and adherence.3

Watch the full interview to hear Schilsky discuss what needs to be shown before once-daily trientine reaches practice and how a planned head-to-head trial with D-penicillamine could support its use as first-line therapy.

References:

1. Schilsky M, Weiss KH, Ashdown T, et al. Can a novel instant release trientine tetrahydrochloride formulation be effective when administered once daily? Results of the TRIUMPH-3 pharmacokinetic study. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.
2. Ala A, Aliu E, Schilsky ML. Prospective pilot study of a single daily dosage of trientine for the treatment of Wilson disease. Dig Dis Sci. 2015;60(5):1433-1439. doi:10.1007/s10620-014-3495-6
3. 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.