The US Food and Drug Administration approved rebisufligene etisparvovec-hopf (Fayuvi), the first treatment for pediatric patients with mucopolysaccharidosis type IIIA.
The rare inherited disease, also known as Sanfilippo syndrome type A, causes progressive damage to the brain and nervous system as well as loss of cognitive, language, and other developmental abilities in pediatric patients. Prior to the approval, treatment was limited to symptom management, with no US Food and Drug Administration (FDA)-approved therapy designed to alter the underlying disease course.
Rebisufligene etisparvovec is administered as a single intravenous infusion and uses modified, noninfectious adeno-associated virus serotype 9 to introduce a functional copy of the SGSH gene into patients’ cells. Delivery of the functional gene permits cells to produce sulfamidase, which is deficient or absent in the disease. The enzyme is involved in lysosomal degradation of heparan sulfate, reducing its accumulation in the brain and body.
The FDA evaluated the safety and effectiveness of rebisufligene etisparvovec in an open-label, single-arm, multicenter study of pediatric patients with mucopolysaccharidosis type IIIA (MPS IIIA). Cognitive outcomes were assessed using mean score changes in patients aged 2 to 5 years. According to the FDA, cognitive function remained stable or improved following treatment relative to an untreated historical control cohort.
Safety data were derived from clinical studies in which pediatric patients received 1 intravenous infusion. Adverse reactions reported in more than 5% of patients included increased liver enzymes and amylase, nausea and vomiting, fever, decreased appetite, and reductions in white blood cell and platelet counts. Thrombotic microangiopathy is among the treatment's safety warnings. The FDA also noted that genomic integration of the introduced genetic material may pose a long-term risk of tumor development.
Administration occurs in a health care setting where infusion reactions can be managed. Patients receive corticosteroids beginning 1 day prior to infusion and continuing for at least 8 weeks following treatment.
Rebisufligene etisparvovec received Orphan Drug, Fast Track, and Breakthrough Therapy designations. Ultragenyx Pharmaceutical, Inc, received FDA approval for the therapy.
Source: FDA
