Ultragenyx Announces Approval of Fayuvi Gene Therapy for Sanfilippo Syndrome Type A

Key Points

• FDA approved FAYUVI (rebisufligene etisparvovec-hopf) for pediatric patients with Sanfilippo syndrome Type A, marking the first approved treatment for the disease.
• The approval was supported by data comparing 17 treated children with 27 untreated patients from a natural history cohort, with follow-up extending to nearly eight years.
• Ultragenyx expects commercial product to be available for shipment to Qualified Treatment Centers within 30 to 60 days.

Ultragenyx announced that the FDA granted standard full approval of FAYUVI (rebisufligene etisparvovec-hopf), also known as UX111, for the treatment of pediatric patients with mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo syndrome Type A). FAYUVI is the first FDA-approved treatment for Sanfilippo syndrome Type A. The company also received a Priority Review Voucher upon approval.

“The approval of FAYUVI reflects years of research from scientists and developers, as well as unwavering support from so many families and patient organizations in the face of a devastating, universally fatal disease with no treatment options. This is a historic milestone for a community that has waited far too long, but has never given up hope,” said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. “We recognize the profound urgency of making this therapy available to families, and our focus now is on supporting timely access in the U.S. as we work closely with treatment centers and payers to support families on the gene therapy treatment journey. FDA approval is an important first step toward our long-term goal to bring this treatment option to families of children with Sanfilippo syndrome Type A around the world.”

“The U.S. FDA approval of FAYUVI is a milestone that the Sanfilippo syndrome Type A community spent decades fighting to achieve: the first-ever treatment for a disease that relentlessly steals a child’s abilities, independence, and future,” said Glenn O’Neill, president and co-founder of the Cure Sanfilippo Foundation, and Terri Klein, CNPM, MPA, president and chief executive officer of the National MPS Society. “This remarkable scientific achievement is the culmination of decades of advocacy, fundraising, collaboration, and perseverance across the Sanfilippo community along with researchers, clinicians, and industry partners who never lost faith that progress was possible. We celebrate by honoring every family who contributed and remembering the children we lost while waiting for this day. Together, we look ahead with renewed hope knowing that this treatment is now approved for children and families affected by this heartbreaking disease.”

About the therapy and disease

Sanfilippo syndrome Type A is an ultra-rare, fatal lysosomal storage disease that primarily affects the brain and is marked by rapid, progressive neurodegeneration beginning in early childhood. Children with Sanfilippo syndrome Type A typically experience progressive global developmental delay, followed by the loss of cognitive, language, and motor function, ultimately leading to early death. The disease is caused by a deficiency of the sulfamidase (SGSH) enzyme, which results in the accumulation of heparan sulfate substrate in cells and progressive damage to the central nervous system.

FAYUVI is a single-dose intravenous AAV9 gene therapy designed to deliver a functional copy of the deficient enzyme gene that can express and replace the SGSH enzyme.

“This gene therapy addresses a pressing unmet clinical need and offers families a promising therapeutic option,” said Kevin M. Flanigan, M.D., director of the Center for Gene Therapy at Nationwide Children’s Hospital and principal investigator on the study that led to its approval. “It is additionally gratifying in that this vector was first developed at Nationwide Children’s more than a decade ago, and its approval highlights our commitment to developing therapies that meaningfully impact children’s health.”

Clinical data supporting approval

The approval was supported by data from the pivotal Transpher A trial and long-term follow-up studies. Clinical data now extend to up to nearly 8 years of follow-up.

• Biochemical efficacy was shown by reduction in cerebrospinal fluid heparan sulfate levels throughout the study and across all age groups.
• Clinical efficacy was assessed based on mean change in Bayley-III Cognitive raw score from 24 to 60 months of age.
• FAYUVI-treated patients from the modified intention-to-treat population (N=17) were compared with untreated patients from an external natural history cohort (N=27).
• FAYUVI-treated patients demonstrated a 23.5 point higher cognitive score over natural history during the study period (p<0.0001).

Access and safety information

Ultragenyx said enrolled patients and caregivers will be able to access support through its UltraCare program. FAYUVI will be available through a network of Qualified Treatment Centers in the U.S., and the company expects commercial product will be available for shipment to those centers within 30 to 60 days. Additional information is expected to be available at fayuvi.com and ultracaresupport.com.

FAYUVI is indicated for the treatment of neurologic manifestations of mucopolysaccharidosis type IIIA in pediatric patients with preserved neurodevelopmental function.

• Warnings and precautions include hepatotoxicity, thrombocytopenia, thrombotic microangiopathy, hypersensitivity and infusion reactions, and risk of malignancy.
• The most common adverse reactions reported at 5% or greater were increased liver enzymes, vomiting, abnormal behavior, diarrhea, pyrexia, decreased white cell count, Cushingoid features, decreased appetite, decreased platelet count, anemia, constipation, nausea, increased amylase, increased alkaline phosphatase, seizure, hepatomegaly, muscle spasticity, hypokalemia, gait disturbance, and adrenal insufficiency.
• Temporary vector shedding occurs primarily through bodily fluids and waste for 3 months after infusion.
• Vaccines should be avoided 30 days prior to treatment and while on corticosteroid therapy.

Please see the full Prescribing Information for FAYUVI.

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