Monopar Files Rolling NDA for ALXN1840 in Wilson Disease

Monopar Therapeutics Inc. has initiated the rolling submission of a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for ALXN1840 (bis-choline tetrathiomolybdate; TMC) in Wilson disease.

If approved, ALXN1840 would become the first FDA-approved Wilson disease therapy with a novel mechanism of action in decades. Current treatment options for Wilson disease have focused primarily on reducing copper accumulation through chelation or limiting intestinal copper absorption.

Wilson Disease Treatment Landscape Remains Focused on Copper Reduction

Wilson disease is a rare autosomal recessive disorder caused by pathogenic variants in the ATP7B gene, which impair biliary copper excretion and result in toxic copper accumulation in tissues, particularly the liver and brain. Patients may develop a range of manifestations, including liver disease and neurological or psychiatric symptoms such as personality changes, tremors, and difficulty with movement, swallowing, or speech.

Current FDA-approved therapies include copper chelators such as penicillamine and trientine, which increase urinary copper excretion, as well as zinc acetate, which reduces intestinal copper absorption.

“Wilson disease is a serious, lifelong condition, and patients and their families have waited a long time for a new treatment option,” said Chandler Robinson, MD, chief executive officer of Monopar, in a statement. “Initiating the rolling NDA submission marks an important milestone in our efforts to bring this novel copper-sequestering therapy to patients.”

ALXN1840 Designed to Promote Copper Mobilization

ALXN1840 (bis-choline tetrathiomolybdate) is an investigational once-daily oral therapy designed to bind and remove excess copper from tissues and blood through a novel mechanism of action. The therapy has received orphan drug designation from the FDA and orphan designation from the European Medicines Agency for Wilson disease.

The therapy is designed to address copper dysregulation by promoting copper mobilization and facilitating removal from the body. Unlike existing Wilson disease therapies that primarily rely on copper chelation or reducing absorption, ALXN1840 is intended to target copper stored in tissues and circulating in the blood.

Phase 3 FoCus Trial Supports NDA Submission

The regulatory submission is supported by findings from the pivotal phase 3 FoCus trial, a randomized, rater-blinded, multicenter study evaluating ALXN1840 compared with standard of care in patients with Wilson disease ≥ 12 years of age.

The trial enrolled 214 patients across 2 cohorts. The treatment-experienced cohort included patients who had received standard of care for more than 28 days, while the second cohort included patients who were treatment-naïve or had received standard of care for 28 days or less. Patients were randomized to receive ALXN1840 or standard of care.

The primary endpoint assessed copper mobilization over 48 weeks using the daily mean area under the effect curve (AUEC) for directly measured non-ceruloplasmin-bound copper (dNCC). ALXN1840 met the primary endpoint, demonstrating significantly greater copper mobilization compared with standard of care over 48 weeks.

According to Monopar, ALXN1840 demonstrated approximately three-times greater copper mobilization compared with standard of care (least squares mean difference, 2.18 µmol/L; P < .0001). Copper mobilization was observed within 4 weeks and sustained through the 48-week treatment period.

ALXN1840 Safety Profile Reported in Clinical Development Program

Across the ALXN1840 clinical development program, Monopar reported 645 patient-years of follow-up across 266 patients. In the FoCus trial, ALXN1840 was generally well tolerated, with most adverse events considered mild to moderate. The most frequently reported adverse event in the ALXN1840 treatment group was a reversible increase in transaminase levels.

The rolling NDA submission allows Monopar to submit completed sections of the application to the FDA for review as they become available. The FDA will determine whether the completed application is accepted for review following submission of all required components.

References

1. Monopar Therapeutics Inc. Monopar Initiates Rolling NDA Submission for ALXN1840 in Wilson Disease. GlobeNewswire News Room. Published July 22, 2026. Accessed July 22, 2026. https://www.globenewswire.com/news-release/2026/07/22/3331283/0/en/monopar-initiates-rolling-nda-submission-for-alxn1840-in-wilson-disease.html

2. ALXN1840.; 2025. Accessed July 22, 2026. https://www.monopartx.com/pipeline/alxn1840