The Food and Drug Administration approved the first treatment ever cleared for Sanfilippo syndrome type A on Sept. 17, authorizing a one-time gene therapy called Fayuvi for a disease that previously had no approved treatment and typically kills patients in their teens. A Disease Sometimes Called “Childhood Alzheimer’s”
Sanfilippo syndrome type A, also known as MPS IIIA, is an inherited disorder in which the body cannot produce sulfamidase, an enzyme needed to break down a molecule called heparan sulfate. Without it, the molecule accumulates in the brain and body. Children with the disease typically develop normally for their first two years, then regress, losing language, cognition and mobility they had already gained, the pattern behind its informal nickname, reported by STAT News.
Median life expectancy without treatment is 15 years. Between 3,000 and 5,000 patients live with the disease in the regions where Fayuvi will be commercially available, according to Ultragenyx, the therapy’s manufacturer.
Cara O’Neill, chief science officer of the Cure Sanfilippo Foundation, said the approval changes what happens the moment a family gets the diagnosis. “This would just finally mean when patients and families receive this shocking diagnosis, they wouldn’t be told to take their kids home and love them. They would be given hope and an action plan for treatment,” O’Neill said, according to STAT News.
How a Single Infusion Rewires the Missing Gene
Fayuvi, known generically as rebisufligene etisparvovec-hopf, uses a modified, non-infectious virus called AAV9 to carry a working copy of the SGSH gene into a patient’s cells. Once delivered, those cells begin producing the sulfamidase enzyme the body was missing, allowing it to break down the heparan sulfate that had been building up and gradually clear existing buildup in the brain and other tissue, according to the FDA’s approval announcement. It’s given once, through an intravenous infusion.
In the pivotal Transpher A trial, 17 treated children between ages 2 and 5 scored an average of 23.5 points higher on the Bayley-III cognitive assessment than 27 untreated children tracked in a separate natural history study, during the 24- to 60-month age window when the disease’s untreated decline is steepest, a difference the FDA listed as statistically significant.
Common side effects included elevated liver enzymes, nausea, vomiting, fever, reduced appetite and lower blood cell counts, and the drug carries warnings for a blood-clotting disorder called thrombotic microangiopathy and a theoretical long-term cancer risk tied to how gene therapies integrate into the genome. The therapy also carries Orphan Drug, Fast Track and Breakthrough Therapy designations from the agency.
“Gene therapy holds tremendous promise for rare diseases like Sanfilippo syndrome type A, and this milestone reflects the FDA’s commitment to action,” acting FDA Commissioner Kyle Diamantas said in the agency’s announcement.
Eight Years of Follow-Up Already Covers More Than Half a Lifetime
The math behind the Transpher A trial is what separates this approval from most early gene therapy data. With median untreated life expectancy at 15 years, the nearly eight years of follow-up now available on the trial’s earliest patients means researchers have already tracked more than half of what an untreated child’s expected lifespan would be, and the treated children are still gaining ground rather than declining.
At the 24- to 60-month mark, the point when untreated children typically start losing skills they’d already learned, the treated group’s cognitive scores kept climbing instead of falling off. For a gene therapy tested in a patient population this small, multiyear durability data of that length is unusual this early in a drug’s life.
Ultragenyx chief executive Emil Kakkis credited the years of trial work and patient families for getting the therapy across the finish line. “The approval of Fayuvi reflects years of research … and unwavering support from so many families,” Kakkis said in the company’s statement. Glenn O’Neill of the Cure Sanfilippo Foundation and Terri Klein of the National MPS Society, in a joint statement carried in the same release, called it “a historic milestone for a community that has waited far too long.”
Ultragenyx said Fayuvi should reach Qualified Treatment Centers for shipment within 30 to 60 days of approval. The company has not disclosed a list price.
