Unmet medical needs

Wilson Disease was uniformly fatal until chelation treatments were developed over a half century ago, however, therapy remains largely unchanged since then and considerable unmet medical needs still exist with respect to efficacy, tolerability and simplicity of dosing regimen.

1. Effective treatment with reduced risk of neurologic worsening

With current treatments, improvement of symptoms can take several years.

Clinical response rates to chelation therapy appear to vary depending on the patient’s initial symptoms, with those with hepatic symptoms generally responding better to treatment than those with neurological symptoms.

  • Initial therapy with chelator therapy can lead to hepatic improvements in around 90% of patients, however after 4 years of treatment
  • Also, initial treatment of patients who present with neurologic symptoms is challenging. More than a third of these patients show no improvement after 4 years of treatment with chelators. This failure to respond to chelation therapy with neurological presentation suggests that, the cerebral damage caused by copper toxicity is irreversible under chelation therapy and demands additional treatment option.
  • Zinc is slow acting and would not be expected to control free copper for 6-12 months, during which time disease can progress.
  • About 50% of patients still suffer from neurological symptoms despite decades of chelation and/or zinc therapy plus symptomatic therapy for their neurological symptoms.

An overall concern is the fact that approx. 25% of patients initiated on penicillamine and trientine experience neurological worsening, and that up to 50% of these patients never recover.

2. Improved safety and tolerability

Currently available therapies have high rates of treatment discontinuation due to adverse events or treatment failure:

  • General chelators like penicillamine or trientine are not specific to copper but also bind to other metals (such as iron and zinc). Many patients receiving chelators develop side effects, some very serious, which can cause up to 30% of patients to discontinue therapy.
  • Gastrointestinal upset is a relatively common side effect of zinc therapy.

It has been reported that up to 75% of patients switch therapy over the duration of their treatment for Wilson Disease, for reasons including side effects.

3. Simplified dosing regimen for improved compliance

Current treatments have complex dosing regimens which may lead to poor compliance.

  • Chelators are administered as oral capsules 2-4 times per day on an empty stomach at least one hour before or two hours after meals, and at least one hour before or after any other pharmaceutical product or milk. This dosing regimen often leads to poor treatment compliance.
  • Zinc is administered as oral capsules up to 5 times per day on an empty stomach at least one hour before or two to three hours after meals.

Easier drug regimens could increase compliance in patients with Wilson Disease, since non-compliance is a significant problem in these patients.

Treatment outcome is worse in non-compliant patients compared to patients that follow or comply with their prescribed dose. Also, non-compliance is higher in clinically presymptomatic patients than the general population of Wilson Disease patients.

Hence, there is a need for improved clinical trials to assess the efficacy and safety of new treatments in Wilson Disease.