REGENXBIO announced the first patient has been dosed in the Phase I/II trial of RGX-111 for the treatment of Mucopolysaccharidosis Type I (MPS I). RGX-111 is an investigational one-time gene therapy designed to deliver the α-l-iduronidase (IDUA) gene directly to the central nervous system (CNS) using the NAV AAV9 vector.

MPS I is a rare, autosomal recessive genetic disease caused by deficiency of IDUA, an enzyme required for the breakdown of the polysaccharides in lysosomes. These polysaccharides, called glycosaminoglycans (GAGs), accumulate in tissues of MPS I patients, resulting in characteristic storage lesions and diverse clinical signs and symptoms including in the central nervous system (CNS), which can include excessive accumulation of fluid in the brain, spinal cord compression, and cognitive impairment.

"We are leaders in the development of one-time treatments using our NAV Technology Platform and proprietary delivery procedure which is designed to administer our gene therapy candidates directly to the central nervous system (CNS). RGX-111 is our second product candidate for the treatment of a rare, neurodegenerative disease to be dosed in patients, following RGX-121, which is in clinical development for MPS II," said Steve Pakola, M.D., Chief Medical Officer of REGENXBIO. "We believe one-time treatment with RGX-111 can provide sustainable IDUA enzyme for patients, potentially preventing the progression of disease. The dosing of the first patient in the clinical trial for RGX-111 marks an important milestone in our neurodegenerative disease program and our commitment to the MPS community."

The Phase I/II trial is a multi-center, open-label, dose escalation trial that will evaluate the safety, tolerability and pharmacodynamics of RGX-111 delivered to patients with MPS I via injection directly into the cerebrospinal fluid (CSF). Up to five patients will be enrolled at two dose levels: 1.0x1010 GC/g of brain mass and 5.0x1010 GC/g of brain mass. The primary endpoint of the study is safety and tolerability of RGX-111. Other endpoints include the effect of RGX-111 on biomarkers of IDUA enzyme activity in the CSF, serum and urine, neurocognitive development and other outcome measures.

RGX-111 is a product candidate for the treatment of Mucopolysaccharidosis Type I (MPS I), also known as Hurler syndrome. RGX-111 is designed to use the AAV9 vector to deliver the α-l-iduronidase (IDUA) gene. Delivery of the enzyme that is deficient within cells in the central nervous system (CNS) could provide a permanent source of secreted IDUA beyond the blood-brain barrier, allowing for long-term cross-correction of cells throughout the CNS. This strategy could also provide rapid IDUA delivery to the brain, potentially preventing the progression of cognitive deficits that otherwise occurs in MPS I patients. RGX-111 has received orphan drug product, rare pediatric disease and Fast Track designations from the U.S. Food and Drug Administration.

MPS I is a rare autosomal recessive genetic disease caused by deficiency of IDUA, an enzyme required for the breakdown of the polysaccharides in lysosomes. These polysaccharides, called glycosaminoglycans (GAGs), accumulate in tissues of MPS I patients, resulting in characteristic storage lesions and diverse clinical signs and symptoms including in the central nervous system (CNS), which can include excessive accumulation of fluid in the brain, spinal cord compression, and cognitive impairment. MPS I is estimated to occur in 1 in 100,000 births. Current disease modifying therapies for MPS I include hematopoietic stem cell transplant (HSCT) and enzyme replacement therapy with a recombinant form of human IDUA administered intravenously. However, intravenous enzyme therapy does not treat the CNS manifestations of MPS I, and HSCT can be associated with clinically significant morbidity and mortality.