FDA Approves First Gene Therapy for Sanfilippo Syndrome Type A
The FDA has approved rebisufligene etisparvovec (Fayuvi) as the first treatment for pediatric patients with mucopolysaccharidosis type IIIA.
The U.S. Food and Drug Administration has approved the first-ever treatment for pediatric patients with mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo syndrome type A. The agency announced the approval of rebisufligene etisparvovec, to be marketed as Fayuvi, on Thursday.
Manufacturer Ultragenyx Pharmaceutical stated the therapy is approved to treat the neurologic manifestations of the disease in children who have preserved neurodevelopmental function. MPS IIIA is an ultra-rare, fatal genetic disorder that causes rapid neurodegeneration in early childhood.
Understanding Sanfilippo Syndrome Type A
The condition is caused by a deficiency in the sulfamidase (SGSH) enzyme. This deficiency leads to a toxic accumulation of heparan sulfate, which progressively damages the central nervous system. Children with the disease experience global developmental delays, followed by a steady loss of cognitive, language, and motor skills. Median life expectancy is just 15 years, a characteristic that has led the condition to be described as a form of childhood dementia.
How the Gene Therapy Works
Rebisufligene etisparvovec is a one-time, intravenous gene therapy. It uses an adeno-associated virus serotype 9 (AAV9) vector to deliver a functional copy of the SGSH gene into the body. This enables the production of the sulfamidase enzyme, allowing heparan sulfate to be properly broken down and reducing its harmful buildup in the brain and body.
Dr. Megha Kaushal, acting deputy director of the FDA's Office of Therapeutic Products, highlighted the significance of the approach. "Achieving meaningful neurodevelopmental benefit through a single intravenous administration represents a significant scientific milestone," Kaushal said. She noted it demonstrates that systemic AAV9-mediated gene delivery can reach the central nervous system at therapeutic levels in pediatric patients.
Clinical Trial Data and Safety
The FDA's approval was based on data from an open-label, single-arm, multicenter clinical trial. The study measured mean changes in cognitive scores in patients aged 2 to 5 years. According to the agency, those who received the gene therapy maintained or improved cognitive function compared with an untreated historical control group.
The therapy's safety profile includes several common adverse reactions and significant warnings. The most frequently reported side effects across clinical studies were:
Safety warnings include the risk of thrombotic microangiopathy. The FDA also issued a specific caution regarding the long-term risks associated with AAV-based gene therapies. As with other AAV-based gene therapies, there is a potential long-term risk that the inserted genetic material could integrate into the genome and potentially lead to tumor development, the agency warned.
This approval follows a previous rejection by the FDA just over a year ago, which was related to manufacturing concerns. Ultragenyx has set the U.S. List price for the one-time treatment at $3.95 million.
