CHICAGO — ALXN1840 (tiomolibdate choline), a first-in-class, investigational copper-binding agent previously known as WTX101, improved clinical outcomes and was generally well tolerated in adults with Wilson disease (WD) in the phase 3 FOCUS trial.

WD is a rare genetic disorder where excessive amounts of copper accumulate in the body; ALXN1840 is an albumin tripartite complex activator.

In the FOCUS trial, patients with neurologic symptoms at baseline who received the oral medication had significantly greater neurologic improvement and less deterioration at 48 weeks than those who received standard of care medications.

Study investigator Peter Hedera, MD, PhD, professor of neurology and director of the Movement Disorders Programs at the University of Louisville, Louisville, Kentucky, said there are now plans to submit a New Drug Application to the FDA in summer or fall of this year.

If the medication receives approval, “as a neurologist I would be in favor of using this as a first-line treatment for the neurologically affected patients,” Hedera told Medscape Medical News.

“Although there are other treatments for [WD], there is still a great unmet need and this could provide a better treatment choice with better outcomes,” he said.

The findings were presented at a late breaking science session at American Academy of Neurology (AAN) 2026 Annual Meeting.

Copper Binder

WD affects approximately 1 in 30,000 people worldwide, with the copper overload caused by ATP7b dysfunction. Toxic amounts of copper can accumulate in the liver, brain, and other organs.

As a tripartite complex activator, ALXN1840 binds copper “with high selectivity and affinity,” Hedera told meeting attendees. He added that the medication sequesters toxic copper and prevents it from crossing the blood-brain barrier.

The global FOCUS trial included more than 200 primarily 20- and 30-year-old patients with WD who were randomly assigned to receive either ALXN1840 (n = 137) or standard of care medications (n = 70) as the active comparator.

The novel drug was administered orally for 48 weeks starting at 15 mg every other day and then titrated up to 60 mg/d. Standard of care treatment was also administered for 48 weeks and included chelating agents such as trientine, penicillamine, and zinc.

At baseline, 56% of the study-drug group and 50% of the comparator group had neurologic symptoms, as measured on the Unified WD Rating Scale (UWDRS) Part III. Hedera noted that these included tremors, parkinsonism, dystonia, and ataxia.

After completing the primary evaluation study period, participants were offered the option to continue treatment with ALXN1840 in an extension phase of up to 5 years.

Persevering Benefits

Results showed that the ALXN1840 group had a higher rate (45%) of neurologic improvement on the UWDRS III at week 48 than the standard of care group (32%), as well as a lower rate of worsening (9% vs 25%; P < .05 for both comparisons).

There was also greater improvement at 48 weeks for the novel treatment vs standard of care on the Clinical Global Impression-Severity (61% vs 17%; P = .008) and Clinical Global Impression-Improvement (47% vs 18.5%; P = .003) scales.

Additionally, neurologic benefit increased over time with ALXN1840 use up to 96 weeks, regardless of whether the participants were experienced with the drug or if they were treatment naive before switching to it during the extension period (P < .05 for both subgroups).

In safety analysis, 4.9% of the ALXN1840 group had any drug-related serious adverse events. Only two patients had neurologic adverse events (both with slight worsening of dysphagia) and one patient had a psychiatric adverse event (depression). No drug-related deaths occurred.

“The safety profile was very favorable, and we saw several benefits that persevered,” Hedera said.

‘Encouraging’ Data

Commenting on the findings session co-moderator Jorg Dietrich, MD, PhD, member of the AAN Science Committee and a neuro-oncologist at Mass General Brigham, Boston, noted that interventions have been “sparse” for this disorder; and of those available, some are associated with adverse neurologic events and/or the treatment regimen can be difficult.

“Seeing a different intervention that has none of those side effects, is easier on patients to take, and is leading to more overall benefits than the existing interventions is encouraging,” Dietrich, who was not involved with the research, told Medscape Medical News.

“Let’s see where this line of treatment will go and if it’s something that can be developed further,” he said.

The study was funded by Alexion Pharmaceuticals. Hedera reported having received conference travel expenses from Monopar Therapeutics, which acquired worldwide license of the drug in 2024, and having served as a member of the DMC for Ultragenyx UX-701 for Wilson disease. Dietrich reported having no relevant financial relationships.