FDA Grants Orphan Drug Designation to EXG110 Gene Therapy for Fabry Disease

• The FDA has granted orphan drug designation to EXG110, a novel gene therapy developed by Exegenesis Bio for Fabry disease.
• EXG110 is designed as a one-time treatment to deliver a genetic payload directly to liver and heart cells, potentially improving efficacy and safety.
• A clinical trial in China has already dosed its first patient, and plans are underway to launch a US-based clinical trial for EXG110.
• Fabry disease, a rare lysosomal disorder, leads to lipid accumulation and can cause renal failure, cardiac disease, and strokes, highlighting the need for new treatments.

The FDA has granted orphan drug designation to EXG110, a novel gene therapy developed by Exegenesis Bio for Fabry disease. This designation aims to facilitate the development and evaluation of EXG110, which is currently being investigated in clinical trials as a potential one-time treatment for this rare and debilitating condition. The first patient has been dosed in a clinical trial in China, and plans are underway to initiate a US-based clinical trial.

Addressing Fabry Disease with Gene Therapy

Fabry disease is a rare lysosomal storage disorder characterized by the accumulation of sphingolipids in various tissues due to a deficiency in the alpha-galactosidase A (alpha-GAL) enzyme. This accumulation can lead to significant health complications, including renal failure, cardiac disease, and strokes. Current treatments involve enzyme replacement therapy or chaperone therapy, but these have limitations and do not represent a cure.

EXG110 is designed to deliver a functional copy of the GLA gene, which encodes the alpha-GAL enzyme, directly to liver and heart cells. By using a proprietary capsid, Exegenesis Bio aims to enhance delivery efficiency, potentially improving both the efficacy and safety profiles of the gene therapy while enabling lower dosing. The goal is to provide a one-time treatment that can address the underlying cause of Fabry disease and reduce the burden of chronic therapy.

Current Treatment Landscape and Unmet Needs

Existing treatments for Fabry disease include bi-weekly enzyme replacement therapy with drugs like agalsidase beta (Fabrazyme) and pegunigalsidase alfa (Elfabrio). Oral chaperone therapy with migalastat (Galafold) is also an option for some patients, but its effectiveness depends on the specific genetic mutation. These treatments aim to manage symptoms and slow disease progression, but they do not offer a cure, and patients often require lifelong therapy.

Clinical Development and Future Directions

With the orphan drug designation, Exegenesis Bio is poised to further advance the clinical development of EXG110. The ongoing clinical trial in China and the planned US-based trial will evaluate the safety and efficacy of this novel gene therapy. According to Zhenhua Wu, PhD, CEO of Exegenesis Bio, the FDA’s decision underscores the need for improved treatment approaches for Fabry disease, which affects thousands globally.

Disease Burden and Patient Impact

Fabry disease can manifest in different forms, with classic Fabry disease typically presenting in childhood or adolescence with symptoms like painful burning sensations in the hands and feet. Late-onset Fabry disease may not show symptoms until later in life, often with kidney or heart complications as the first signs. The disease affects approximately 1 in 40,000 individuals for the classic form and 1 in 1,500 to 4,000 men for the atypical form. Women can also be affected, though symptoms may be milder or more variable due to X-chromosome inactivation, leading to delayed diagnosis.