Data from the first patients enrolled in Regenxbio's trial of its gene therapy for mucopolysaccharidosis type I (MPS I), also known as Hurler syndrome, has shown the first signs of clinical activity. The results come from five patients in the ongoing phase 1/2 study of RGX-111, which uses an adeno-associated viral vector (AAV9) to deliver a gene coding for an enzyme deficient in MPS I patients, plus a single subject from an earlier study.
In MPS I, the lack of alpha-l-iduronidase (IDUA) inhibits the ability of cells to break down waste sugar molecule chains, leading to their accumulation in tissues with toxic effects, particularly in the central nervous system. Severe cases result in significant cognitive impairment. Current treatments include a risky haematopoietic stem cell transplant (HSCT) or weekly infusions with BioMarin's enzyme replacement therapy Aldurazyme (laronidase).
Regenxbio's RGX-111 aims to offer a one-shot treatment by delivering a functional copy of the IDUA gene to cells in the CNS. Initial data from the phase 1/2 trial revealed no drug-related serious adverse events, positive effects on IDUA biomarkers in the CNS, and preliminary evidence of improved neurodevelopment. Three patients showed improvements in skills like cognition, expressive language, and fine motor skill acquisition.
The subject from the initial study that led to FDA approval of the phase 1/2 trial also showed better-than-expected improvements over a follow-up period of around 20 months. These early results are encouraging, according to Ray Wang, a specialist in metabolic disorders at the University of California, Irvine, highlighting the limitations and risks associated with current treatment options for MPS I.
Regenxbio plans to recruit another six patients into the phase 1/2 study, which involves administration of the gene therapy directly into the central nervous system. This development marks a significant step forward in the search for effective treatments for MPS I, offering hope to patients and families affected by this challenging condition.
