The FDA has approved rebisufligene etisparvovec-hopf (brand name Fayuvi) as the first gene therapy for children with Sanfilippo syndrome type A. This approval introduces the first disease-modifying treatment for this rare, inherited neurodegenerative disorder, marking a significant shift in managing mucopolysaccharidosis type IIIA (MPS IIIA). Previously, care focused solely on symptom management and supportive measures.
Fayuvi is administered as a one-time intravenous (IV) infusion, targeting the root cause of MPS IIIA: an enzyme deficiency. It uses an adeno-associated virus serotype 9 (AAV9) vector to deliver a functional copy of the SGSH gene to patients’ cells, enabling them to produce sulfamidase, the enzyme critical for breaking down heparan sulfate.
A Disease of Accumulation
MPS IIIA is a lysosomal storage disorder caused by pathogenic variants in the SGSH gene, leading to sulfamidase deficiency. The progressive buildup of heparan sulfate in cells, particularly within the central nervous system, drives cognitive decline, behavioral changes, speech loss, motor impairment, and other disease manifestations. Children with MPS IIIA often develop typically initially but then experience a plateau followed by regression, ultimately facing severe neurological deterioration and a shortened lifespan.
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A New Approach
Fayuvi’s systemic delivery is designed to allow the AAV9 vector to reach the central nervous system at therapeutic levels. By enabling cells to produce sulfamidase, the therapy reduces harmful heparan sulfate accumulation in the body and brain, potentially slowing disease progression. The approval was based on a clinical trial demonstrating that treated children maintained or improved cognitive function compared to untreated children, a significant departure from the expected natural history of MPS IIIA.
Safety and Monitoring
Common side effects include nausea, vomiting, fever, and decreased appetite, along with laboratory abnormalities like increased aspartate aminotransferase and amylase levels. A rare but serious risk is thrombotic microangiopathy, a condition affecting small blood vessels. There is also a theoretical long-term risk of tumor development due to potential integration of the gene therapy vector into the patient’s genome. All patients receive corticosteroid therapy starting one day before infusion and continuing for at least 8 weeks to manage potential reactions.
Pharmacists play a critical role in medication management, verifying weight-based corticosteroid regimens, assessing interactions, monitoring adherence, and coordinating laboratory surveillance. They also support families by explaining the infusion process, reinforcing treatment instructions, and reviewing adverse-effect warning signs.
