Experimental MPS 1 Therapy Shows Biomarker Activity, Improved Function

Gene Therapy


REGENXBIO presented results Wednesday from its ongoing Phase I/II trial of RGX-111, an investigational one-time gene therapy for people with Mucopolysaccharidosis Type I (MPS I). The data, presented at the 18th annual WORLDSymposium, represented six patients diagnosed with severe MPS I who were treated with RGX-111.

Mucopolysaccharidosis Type I is a rare, genetic condition that can affect many parts of the body. The condition stems from a mutation in the IDUA gene which provides instructions for producing an enzyme that is involved in the breakdown of large sugar molecules. In people with MPS I, the gene reduces or completely eliminates the enzymes needed for the breakdown of large sugar molecules, leading to the accumulation of these molecules in cells called lysosomes, whose function is to digest and recycle molecules. The lysosomes become enlarged, causing significant issues in multiple organs including decline in central nervous system (CNS) functioning.

Signs and symptoms of MPS I appear during childhood, and it is a progressively debilitating disorder. Most commonly, people with MPS I experience frequent upper respiratory infections, sleep apnea, hydrocephalus or buildup of fluid in the brain, ear infections and hearing loss, heart valve abnormalities and joint deformities. People with the severe form of the disease experience significant declines in intellectual functioning. Children with severe disease have a shortened lifespan, sometimes only living into late childhood.

REGENXBIO reported that RGX-111 was well-tolerated in patients, showing encouraging continued neurodevelopment and biomarker activity in the central nervous system, meeting the primary and secondary endpoints of the trial. Patients also showed encouraging skill acquisition after treatment. No drug-related serious adverse events have been reported.

The therapy is designed to deliver the gene that encodes the IDUA enzyme using the adeno-associated virus serotype 9 (AAV9) vector, which has the ability to traverse the blood-brain barrier to target the central nervous system. The drug is intended to provide a permanent source of secreted IDUA beyond the blood-brain barrier, allowing for long-term cross-correction of cells throughout the CNS, which could potentially help prevent the progression of cognitive deficits.  

“This marks our first data presentation from the Phase I/II trial evaluating RGX-111 as a potential one-time gene therapy delivered directly to the central nervous system for the treatment of severe MPS I. We are encouraged to see that RGX-111 has been well-tolerated with emerging evidence of CNS biomarker activity and improvements in neurodevelopmental function, which suggest biological activity in the CNS following one-time administration of RGX-111,” said REGENXBIO Chief Medical Officer Steve Pakola, M.D. “We also saw emerging evidence of biomarker activity outside of the CNS. We plan to enroll additional patients in the Phase I/II trial and look forward to providing additional updates."

Current treatments for MPS I include hematopoietic stem cell transplant and enzyme replacement therapy with a recombinant form of human IDUA administered intravenously. However, enzyme therapies do not treat CNS manifestations of MPS I. REGENXBIO’s emerging therapeutic would provide a one-time treatment that could potentially alleviate many cognitive concerns that progress throughout the life of a patient.

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