Rare Diseases: Phase FIH/I Wilson’s Disease

Wilson’s Disease

Wilson’s Disease is a rare autosomal recessive genetic disorder caused by mutations in the ATP7B gene, leading to impaired copper transport and accumulation in vital organs such as the liver, brain, and eyes. The global prevalence is estimated at approximately 1 in 30,000 individuals, with a carrier frequency of 1 in 90¹.

Current Therapeutic Solutions

Standard treatments for Wilson’s Disease include:

• Chelating Agents: Medications like trientine and d-penicillamine that bind excess copper for excretion.
• Zinc Supplements: Reduce copper absorption in the gastrointestinal tract.
• Dietary Modifications: Adherence to a low-copper diet to minimize intake.
• Liver Transplantation: Considered in severe cases with liver failure.

While these treatments manage copper levels, they do not address the underlying genetic cause. Also, the burden of a life-long, constraining medical treatment leads to poor adherence, and up to 50% non-compliance has been reported. Recent advancements in gene therapy offer promising avenues for more definitive treatments.

Challenges for Patients

In a healthy body, the liver filters out excess copper and releases it through the bile. With Wilson Disease, the liver can’t remove the extra copper properly. This leads to excess copper build up in organs such as the brain, liver, and eyes leading to organ damage.

The disease is progressive: it can cause liver (hepatic) disease, central nervous system dysfunction and if left untreated, it can be fatal. Early diagnosis and treatment can therefore prevent serious long-term disability and life-threatening complications.

Aixial Group’s Solution

The team at Aixial Group drew on their expertise to support a Phase I First In Human trial with a European biotechnology company using an adeno-associated viral vector (AAV)-based gene therapy. The patients received an ascending dose of the treatment.

Complex studies such as this have challenges in both the set-up and execution phases, for this study in particular there were challenges associated with both the gene therapy product and challenges associated with the production, delivery and administration of a radiopharmaceutical product being used as an assessment tool. Aixial Group mitigated these risks with the following strategies:

• Performing Comprehensive Feasibility Studies Early On: Assessing trial viability and identifying optimal sites for patient recruitment.
• Designing and Implementing Robust Monitoring Protocols: Implementing advanced monitoring systems to ensure participant well-being with our multifaceted approach combining technology and on-site monitoring coupled with expert Data Monitoring Committee and Hepatic Adjudication Committee review.
• Developing a Strong Regulatory Pathway: Using experience in both the gene therapy and radiopharmaceutical space to navigating complex regulatory landscapes, complex submissions and multiple committee reviews to facilitate smooth trial progression.
• Providing 24/7 medical monitoring coverage and work closely with Investigators to effectively manage infusion related reactions and other associated safety issues.

By leveraging our team’s expertise, we continue to successfully support our Sponsors conducting early phase studies in rare diseases, like Wilson’s Disease, contributing to the advancement of innovative therapies that address unmet medical needs.