FDA approves first gene therapy for Sanfilippo syndrome type A, marking a new milestone for rare disease

The US Food and Drug Administration (FDA) has approved the first gene therapy for Sanfilippo syndrome type A (MPS IIIA), a rare neurodegenerative disease.

According to Fierce Pharma on the 17th local time, the FDA approved Ultragenyx’s gene therapy Fayuvi as the first treatment for children with MPS IIIA.

MPS IIIA is caused by a deficiency of the sulfatase enzyme resulting from mutations in the SGSH gene. Without this enzyme, heparan sulfate accumulates in cells, damaging the brain and gradually causing children to lose developmental abilities, including cognition and language.

Ultragenyx estimated that approximately 3,000 to 5,000 patients in developed countries have the disease.

Fayuvi uses an adeno-associated virus (AAV) vector to deliver a normal SGSH gene to patients’ cells. Unlike existing treatments, which are limited to managing symptoms, it is the first FDA-approved treatment to target the underlying cause of the disease.

Acting FDA Commissioner Kyle Diamantas said, “Fayuvi’s approval is a historic moment for children with MPS IIIA and their families, who until now have had no approved treatment capable of changing the devastating course of the disease.”

Ultragenyx was previously denied FDA approval last year because of manufacturing-related issues at its own gene therapy manufacturing facility and a third-party contract manufacturing organization. The company said it currently manufactures Fayuvi at its own facility in Bedford, Massachusetts, and through Andelyn Biosciences in Columbus, Ohio.

The FDA accepted the resubmission in April and granted it priority review.

Clinical data showed that a single intravenous infusion of Fayuvi in 17 children who were younger than 2 years or in the early stages of the disease at the time of treatment resulted in a positive treatment effect of 23.2 points on cognitive scores measured by the Bayley-III, compared with natural history data.

Eight of these children reached a cognitive developmental age of 36 months, while no patients in the natural history group reached this threshold.

Among 10 older children or those in later stages of the disease, functional maintenance was observed in at least one of three domains at the last assessment. This exceeded the typical pattern of decline in untreated patients.

Ultragenyx CEO Emil Kakkis said, “We understand the urgency of making this treatment available to families,” adding, “We will focus on working closely with treatment centers and insurers to support timely access in the United States.”

Fayuvi is Ultragenyx’s second FDA approval in less than a month. Earlier, the FDA granted accelerated approval to the company’s glycogen storage disease type Ia (GSDIa) treatment, Zenglicos.

However, the company has faced clinical setbacks, including the phase 3 failure of apazunersen, a candidate treatment for Angelman syndrome, earlier this month. According to Fierce Pharma, the fallout sent the company’s stock to an all-time low this month, and the company is considering significant cost reductions.

The approval comes after a period in which the FDA applied stringent standards to rare disease approvals. Since then, the FDA has approved Denali Therapeutics’ enzyme replacement therapy Ablaya as a treatment for Hunter syndrome (MPS II).