About Wilson Disease

Wilson disease is a rare and progressive genetic condition in which the body’s pathway for removing excess copper is compromised. ¹ It affects one in 30,000 live births in the US.¹ Over time this results in the build-up of toxic copper levels in the liver, brain, and other organs, leading to damage that greatly impacts a patient’s life. ¹ Patients can develop a wide range of symptoms, including liver disease and/or psychiatric or neurological symptoms, such as personality changes, tremors, and difficulty walking, swallowing or talking. ¹ In some cases, the damage and loss of function may be irreversible. ^1,2,3

About ALXN1840

ALXN1840 (bis-choline tetrathiomolybdate) is an investigational once-daily, oral medicine in development for the treatment of Wilson disease. This novel molecule is designed to selectively and tightly bind and remove copper from the body’s tissues and blood. ALXN1840 has been granted Orphan Drug Designation in the United States and orphan designation in the European Union for Wilson disease.

About the Phase 3 “FoCus” Clinical Trial

The FoCus trial was a pivotal Phase 3, randomized, rater-blinded, multi-center clinical trial designed to evaluate the efficacy and safety of ALXN1840 versus standard-of-care (SoC) in patients with Wilson disease aged 12 years and older. The primary endpoint assessed copper mobilization over 48 weeks, defined as daily mean AUEC (Area Under the Effect Curve) for dNCC (directly measured non-ceruloplasmin-bound copper). In the trial, 214 patients were enrolled in one of two cohorts on a 3:1 basis (treatment-experienced : treatment-naïve). Each cohort was then randomized 2:1 (ALXN1840 : SoC). The first cohort enrolled 161 patients who received SoC (chelation therapy with penicillamine or trientine, zinc therapy or a combination of both chelation and zinc therapy) for more than 28 days and the second cohort enrolled 53 patients who were treatment-naïve or had received SoC for 28 days or less. The FoCus trial met its primary endpoint demonstrating three-times greater copper mobilization from tissues compared to the SoC arm (Least Square Mean Difference [LSM Diff] 2.18 µmol/L; p< 0.0001), including in patients who had been treated previously for an average of 10 years. In the trial, people taking ALXN1840 experienced rapid copper mobilization, with a response at four weeks and sustained through the 48 weeks. ALXN1840 was generally well-tolerated with most reported adverse events considered mild to moderate, and no neurological worsening upon initiation of treatment was observed. In the ALXN1840 treatment group, the most frequently reported adverse event was a reversible increase in transaminase levels.

1. Patil, M., et al. (2013) J Clin Exp Hepatol, 3, 321-336.
2. Roberts, E.A., Schilsky, M.L. American Association for the Study of Liver D. (2008). Diagnosis and treatment of Wilson disease: An update. Hepatology, 47(6), 2089-2111.
3. European Association for the Study of the Liver. (2012). EASL clinical practice guidelines: Wilson’s disease. J Hepatol, 56(3), 671-685.