AstraZeneca Looks to Add to Small Group of Wilson Disease Drugs With It's ALXN1840

ALXN1840 drug has shown positive results in phase III study. (Courtesy of Bodo Marks/picture alliance/Getty Imag)

ALXN1840 drug has shown positive results in phase III study. 

Courtesy of Bodo Marks/Picture Alliance/Getty Images

An experimental AstraZeneca drug for Wilson disease hit the mark in a Phase III study in which the drug, ALXN1840, was able to achieve three times greater mobilization of copper than the standard of care.

In those with Wilson disease, excess copper build-up in organs and tissues caused by the loss of the ATP7B protein required for copper transport can lead to liver disease, as well as neurological and psychiatric symptoms. It is estimated that about 9,000 people in the U.S. have been diagnosed with the disorder.

There are only a handful of drugs approved by the FDA to treat this genetic disorder, including Syprine, a medication that’s been around since the 1960s, and the more-recently-approved Cuvrior, developed by France-based Orphalon. Based on data from the Phase III FoCus study, AstraZeneca hopes to join this small group of medications approved by the U.S. Food and Drug Administration.

In the Phase III study, which has been billed as the largest global trial in Wilson disease to date, ALXN1840 met its primary endpoint by demonstrating a copper mobilization three times greater than the standard of care, including patients who have previously been treated for at least 10 years. Even after standard of care treatment, some patients continue to see a progression of their disease and a worsening of neurological symptoms, AstraZeneca said.

Trial data showed that patients experienced copper mobilization, which is the filtering of copper buildup, within four weeks and sustained through 48 weeks, the company said. In patients who were symptomatic of Wilson disease at baseline, treatment with ALXN1840 generated greater improvements in neurological scores than the standard of care. This data was a secondary endpoint of the study. However, AstraZeneca noted that in this subgroup, there were no significant differences between treatment groups seen at 48 weeks.

AstraZeneca noted that most patients in the trial had low symptom scores at baseline, which it said indicated minimal room for total score improvement. As people with Wilson disease experience a highly varied degree of symptoms, this total score may not reflect the extent of disease severity, AstraZeneca said.

ALXN1840 was well tolerated in the FoCus study, and long-term safety and efficacy is being assessed in an up to 60-month extension period. AstraZeneca intends to present full data from the Phase III FoCus study today at the 2022 International Liver Congress in London.

ALXN1840, which was developed by AstraZeneca’s rare disease subsidiary Alexion, is an investigational molecule designed to bind with and remove copper from the body. ALXN1840 has been granted Orphan Drug Designation in the United States and orphan designation in the European Union for Wilson disease.

Marc Dunoyer, the chief executive officer of Alexion, noted that many Wilson disease patients can continue to experience symptoms even after years of using available therapies. He said that demonstrates a significant need for the re-evaluation of the standard of care used to treat this genetic disorder.   

“Applying our 30 years of experience in rare disease clinical development, Alexion has conducted rigorous scientific research to bring fresh thinking to Wilson disease around the importance of copper mobilization from the tissues. These data of ALXN1840 drug further our efforts to potentially introduce a novel treatment for patients who have gone decades without meaningful innovation,” Dunoyer said in a statement.

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