Unmet needs in Wilson Disease

Although pharmaceutical products are available for the treatment of Wilson Disease, significant unmet medical needs still exist with respect to efficacy, side effects and simplicity regarding the dosing regimen.

The process of reducing free copper levels associated with the currently available pharmaceutical products is relatively slow and symptoms can take several years to improve. Treatment of patients with neuropsychiatric presentation (approximately 50 percent of all Wilson Disease patients) is an area of particular concern since approximately 30 to 40 percent of the patients are considered non-responders to chelator therapy and approximately 50 percent of neurological patients have residual neurological symptoms despite years of either penicillamine or trientine therapy. Penicillamine or trientine binds non-specific to copper and also bind to other metals like iron, zinc and calcium and have in many cases very serious side effects, which frequently cause patients to discontinue therapy. One of the most serious side effects is that patients suffering from neurological symptoms experience a drug-induced worsening of neurological symptoms shortly after initiation of therapy. Studies show that approximately 25 percent of patients initiated on penicillamine and trientine experiencing this worsening and up to 50% of these patients never recover. Penicillamine or trientine should be taken up to four times daily on an empty stomach which often leads to poor treatment compliance.

Zinc is not recommended as an initial therapy of symptomatic patients with Wilson Disease because of the slow onset of action. Zinc therapy has shown to be less efficacious than chelation therapy and gastrointestinal upset is a relatively common side effect. Like penicillamine and trientine, zinc should also be taken multiple (up to five) times per day on an empty stomach.

Studies have shown that up to 45 percent of patients treated with current products do not adhere to their prescribed medications and that treatment outcome is worse in these patients compared to patients that follow or comply with their prescribed dose.