After Ultomiris stumble, Alexion delivers a rare disease win for AZ

A drug for Wilson disease developed by AstraZeneca's Alexion rare disease unit has cleared a phase 3 trial, setting up regulatory filings in the coming months.

The FoCus study of ALXN1840 showed that once-daily oral drug met its primary objective in improving a key biomarker in Wilson disease, a rare and progressive genetic condition in which the body's pathway for removing excess copper is compromised allowing it to build to toxic levels.

In the trial, treatment with ALXN1840 improved copper mobilisation from tissues, a surrogate marker indicating that levels within tissues are going down. If untreated, excess copper can lead to liver damage as well as central nervous system disorders.

The positive result is a boost for AZ, which shelled out $39 billion to buy Alexion earlier this year, coming just a few days after Ultomiris (ravulizumab) – the primary asset driving the acquisition – failed to show efficacy in rare neurodegenerative disease amyotrophic lateral sclerosis.

Wilson disease can't be cured, but can be treated with chelation agents like penicillamine or trientine, zinc therapy or a combination of the two, which work by removing copper from the blood. If treatment is prompt and effective, patients can live a normal lifespan, but left untreated the disease can be fatal.

Side effects are common and unpleasant with current treatment – including skin rash and blisters, vomiting and diarrhoea, and wounds that do not heal – so compliance an be poor.

In FoCus, ALXN1840 was more three times effective than the standard treatment in mobilising copper from tissues, according to AZ. The trial involved 214 patients, including subjects both new to treatment and already on chelation therapy for several years, and looked at the effects of treatment over 48 weeks.

In addition to the biomarker data the study will also compile patient-reported outcomes and clinical assessment of disease status, which will be presented at a future medical meeting, said the company.

Alexion acquired ALXN1840 when it bought Wilson Therapeutics for $855 million in 2018, and it has been tipped as a potential blockbuster, marking the first major improvement in the treatment of people with the disease in more than three decades.

The drug could lead to a to redefinition in the treatment goals for Wilson disease, by shifting from a focus on blood copper levels to a "total body de-coppering" approach, according to Alexion.

There are rival therapies for Wilson disease coming through the pipeline, including Vivet Therapeutics' one-shot gene therapy VTX-801, which aims to treat the underlying defect that leads to impaired copper metabolism and is currently in a phase 1/2 trial.

Another gene therapy from Ultragenyx – UX701 – is in early development with human testing due to start later this year.