ALXN1840 is a potential once-daily oral therapy from Alexion, a division of AstraZeneca. It is being developed as a treatment for Wilson disease. This novel, experimental molecule is intended to tightly and selectively bind copper and eliminate it from the body tissues and blood. ALXN1840 has been granted Orphan Drug designation in the United States and Orphan designation in the European Union for the treatment of Wilson disease.1

Impaired copper metabolism is a hallmark of Wilson disease, which is caused by malfunctioning ATP7B protein. The clinical effects of Wilson Disease range from asymptomatic forms to fulminant hepatic failure, chronic liver disease with or without cirrhosis, and neuropsychiatric features.2

The majority of cases can be successfully treated with current Wilson disease therapies, which are based on medications that reduce copper levels in the body, such as chelating agents and zinc salts, and are generally beneficial if used for life. The quest for alternative therapeutic options has been prompted by the numerous limitations of current therapies.3 The experimental treatment, ALXN1840, has shown acceptable results in clinical trials and is generally well tolerated.4,5 

Mechanism of Action

ALXN1840 (bis-choline tetrathiomolybdate) is an oral, targeted decoppering therapy with a unique mechanism of action.6 Originally known as WTX101, bis-choline-tetrathiomolybdate binds tightly to copper and copper-binding proteins and has a substantially higher affinity for copper than other chelators used to treat Wilson disease, such as D-penicillamine and trientine. While other chelators promote the elimination of copper through the urine, ALXN1840 decreases plasma non-ceruloplasmin-bound copper by building tripartite complexes with albumin, targets hepatic intracellular copper, and accelerates biliary copper excretion.7 

Read more about experimental therapies for Wilson disease

Efficacy in Clinical Trials

In humans, the pharmacokinetic profile of ALXN1840 was initially evaluated in a phase 1 trial in 18 patients with advanced solid tumors that were unresponsive to standard therapy.7

In another open-label phase 2 trial (NCT02273596)8 including 28 patients with Wilson disease, ALXN1840 was administered once in a day for 24 weeks. The potential therapy had a good safety profile, and it decreased plasma non-ceruloplasmin-bound copper levels and disease-related disability.7 

The efficacy and safety of ALXN1840 against standard-of-care (SoC) medication were compared in Wilson disease patients aged 12 and above in an ongoing pivotal randomized, rater-blinded, multicenter phase 3 trial called FoCus (NCT03403205).9 SoC included chelation therapy, zinc therapy, or a combination of both. The study included 214 participants, including patients who had never received SoC medication and those who had been receiving it for 10 years or more.4 

The primary goal of the study was to assess copper mobilization using the daily mean area under the effect curve for non-ceruloplasmin-bound copper, which was measured directly over 48 weeks. Positive high-level trial data demonstrated that ALXN1840 was superior to SoC and significantly improved daily mean copper mobilization from the tissues. Additionally, compared to SoC, the experimental treatment increased copper mobilization by almost 3 times.4

The most frequently reported adverse event in the ALXN1840 treatment group was a reversible elevation in transaminase levels. The majority of adverse events associated with ALXN1840 were mild to moderate in severity. There was no evidence of neurological deterioration related to the potential therapy. Additional research is being conducted, including functional evaluations provided by clinicians and particular patient-reported outcomes.4,5 The long-term safety and efficacy of ALXN1840 are being evaluated over an extension period of up to 60 months.1


  1. ALXN1840 shows rapid and sustained improvement in copper mobilisation from tissues, potentially closing treatment gaps for Wilson disease community. News release. AstraZeneca; June 23, 2022.
  2. Rodriguez-Castro KI, Hevia-Urrutia FJ, Sturniolo GC. Wilson’s disease: a review of what we have learned. World J Hepatol. 2015;7(29):2859-2870. doi:10.4254/wjh.v7.i29.2859
  3. Litwin T, Dzieżyc K, Członkowska A. Wilson disease—treatment perspectives. Ann Transl Med. 2019;7(Suppl 2):S68. doi:10.21037/atm.2018.12.09
  4. Alexion’s drug meets primary goal in phase III Wilson disease trial. Clinical Trials Arena. August 27, 2021. Updated July 11, 2022. Accessed September 19, 2022.
  5. ALXN1840 FoCus phase III trial in Wilson disease met primary endpoint demonstrating improvement in copper mobilisation from tissues. News release. AstraZeneca; August 26, 2021.
  6. Pipeline: advancing our pipeline every day. Alexion. Accessed September 19, 2022.
  7. Kim P, Zhang CC, Thoröe-Boveleth S, et al. Analyzing the therapeutic efficacy of bis-choline-tetrathiomolybdate in the Atp7b-/- copper overload mouse model. Biomedicines. 2021;9(12):1861. doi:10.3390/biomedicines9121861
  8. Efficacy and safety study of WTX101 (ALXN1840) in adult Wilson disease patients. October 24, 2014. Updated September 29, 2021. Accessed September 19, 2022.
  9. Efficacy and safety of ALXN1840 (administered for 48 weeks versus standard of care in participants with Wilson disease. January 18, 2018. Updated May 9, 2022. Accessed September 19, 2022.

Reviewed by Hasna Avcu, MD, on 9/25/2022.