Ultragenyx's UX111 Gene Therapy Shows Promise in Sanfilippo Syndrome Type A

Key Insights

• UX111 (rebisufligene etisparvovec) is an investigational gene therapy for Sanfilippo syndrome type A (MPS IIIA), a rare and fatal lysosomal storage disease.
• The therapy uses an AAV9 vector to deliver a functional copy of the SGSH gene, addressing the underlying enzyme deficiency that causes heparan sulfate accumulation.
• UX111 has received multiple designations, including Regenerative Medicine Advanced Therapy and Orphan Drug status, highlighting its potential impact on this unmet medical need.

Ultragenyx Pharmaceutical is developing UX111 (rebisufligene etisparvovec), a novel in vivo gene therapy, as a potential treatment for Sanfilippo syndrome type A (MPS IIIA). This rare, fatal lysosomal storage disease, also known as mucopolysaccharidosis type IIIA, is characterized by rapid neurodegeneration due to the accumulation of heparan sulfate in the central nervous system (CNS). With no approved treatments currently available, UX111 represents a significant advancement in addressing this unmet medical need.

Understanding Sanfilippo Syndrome Type A

MPS IIIA affects an estimated 3,000 to 5,000 patients in commercially accessible regions and typically results in a median life expectancy of just 15 years. Children with MPS IIIA experience global developmental delays, progressive cognitive and language decline, behavioral abnormalities, and ultimately, early death. The disease is caused by biallelic pathogenic variants in the N-sulfoglucosamine sulfohydrolase (SGSH) gene, leading to a deficiency in the sulfamidase enzyme. This enzyme is crucial for breaking down heparan sulfate, a glycosaminoglycan. The deficiency results in the accumulation of heparan sulfate within cells throughout the body, leading to the severe neurodegeneration associated with the disorder.

UX111: A Gene Therapy Approach

UX111 is designed as a one-time intravenous infusion that utilizes a self-complementary AAV9 vector to deliver a functional copy of the SGSH gene directly to cells. By addressing the underlying sulfamidase enzyme deficiency, UX111 aims to reduce the abnormal accumulation of heparan sulfate in the brain, thereby mitigating progressive cell damage and neurodegeneration. The therapy is currently under evaluation in the pivotal Transpher A trial.

Regulatory Designations

The UX111 program has received several important designations that underscore its potential. In the United States, it has been granted Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations. In the European Union, UX111 holds PRIME and Orphan Drug designations. These designations are intended to accelerate the development and review of promising therapies for serious or life-threatening conditions.