Clinical trials can be beneficial for finding and evaluating new treatment options. Recently, biopharmaceutical company AstraZeneca shared how ALXN1840, a potential treatment for patients with Wilson disease, reached its primary endpoint in the Phase 3 FoCus clinical trial. AstraZeneca acquired Alexion Pharmaceuticals (“Alexion”) earlier this year, and was able to take on this drug then. Altogether, the clinical trial highlighted how ALXN1840 was not only safe and well-tolerated but improved daily copper metabolism. 

ALXN1840

So what exactly is ALXN1840? According to Alexion, ALXN1840 is:

A novel oral copper-protein binding agent with a unique mechanism of action, under investigation for Wilson disease, a rare, chronic, genetic, and potentially life-threatening liver disorder of impaired copper transport.

The therapy, which has earned Orphan Drug designation in both Europe and the United States, works to selectively bind to and remove copper from bodily tissue and blood. Researchers evaluated the safety, efficacy, and tolerability of the treatment within the Phase 3 FoCus trial. 

Altogether, 214 patients (aged 12+) with Wilson disease enrolled in the trial. Later, patients were divided into two cohorts: one of whom had previously been treated with the standard-of-care for more than 28 days, and one of whom had been previously untreated or treated with the standard-of-care for shorter than 28 days. Researchers wanted to also understand how ALXN1840 benefited patients as opposed to the standard-of-care, which is defined as chelation therapy, zinc therapy, or both in conjunction. Patients within the study were treated with ALXN1840 for a 48-week period, with the opportunity to continue into an extension study for up to 60 months (5 years). 

Findings from the FoCus study include:

• ALXN1840 was relatively safe and well-tolerated. While some adverse reactions did occur, these were mostly mild and reversible. 
• On average, ALXN1840 helped improve daily copper metabolism more than current treatment options. 

Wilson Disease

ATP7B gene mutations cause Wilson disease, a rare inherited condition which prevents the body from adequately metabolizing and excreting copper. Although copper is necessary to maintain good health, an excess of copper can cause a variety of health issues. Typically, patients with Wilson disease begin experiencing copper accumulation in the brain, liver, and organs at birth. As this progresses over the years, Wilson disease may cause hepatitis, psychiatric issues, or even severe organ damage. Without treatment, Wilson disease is fatal. Although symptoms usually appear in teenage years, ages could range from 6-45. Symptoms include:

• Jaundice (yellowing of the skin and eyes)
• Neutropenia (low white blood cell count)
• Fluid buildup in extremities
• Difficulty walking or swallowing
• Abdominal swelling
• Easy bruising and bleeding
• Kayser-Fleisher ring (brown iris ring)
• Hepatitis
• Suicidal ideations

Learn more about Wilson disease.