FDA approves new gene therapy as first treatment for Sanfilippo A
Infusion therapy Fayuvi to be shipped to treatment centers within 60 days
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The U.S. Food and Drug Administration (FDA) approved the gene therapy Fayuvi (rebisufligene etisparvovec-hopf, formerly known as UX111) as the first treatment for Sanfilippo syndrome type A.
Ultragenyx Pharmaceutical said it expects the drug to be shipped to qualified treatment centers (QTCs) — institutions with expertise and training in gene therapy administration — in 30 to 60 days. The Fayuvi website has a regularly updated list of centers that will administer the treatment.
“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,” Emil D. Kakkis, MD, PhD, CEO and president of Ultragenyx, said in a company press release.
The approval late Thursday came a few days earlier than anticipated; the FDA had been expected to issue a decision by this Saturday. In a press release from the FDA, Kyle Diamantas, the agency’s acting commissioner, said the approval “marks a historic moment for children and families living with [Sanfilippo A], which is a disease that has, until now, offered no approved treatment to alter its devastating course.”
“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,” Kakkis said. “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.”
Treatment aims to slow disease progression
Sanfilippo syndrome type A is caused by mutations in the SGSH gene, which is needed to break down a sugar molecule called heparan sulfate. Without a working version of this gene, heparan sulfate builds to toxic levels in brain cells, causing damage that leads to Sanfilippo symptoms.
Fayuvi aims to deliver a healthy version of the SGSH gene to cells, with the goal of clearing toxic heparan sulfate and slowing disease progression. The therapy delivers its genetic payload using a viral vector, a virus engineered to deliver a therapeutic gene rather than cause infection. The treatment is indicated for use in pediatric patients with preserved neurodevelopmental function.
The one-time gene therapy is administered by infusion into the bloodstream, a process that takes about one hour. One day prior to administration of Fayuvi, patients should start taking corticosteroids, anti-inflammatory medications that can help reduce the risk of adverse immune reactions to the viral vector. Corticosteroids should be continued for at least eight weeks, then tapered off.
According to its prescribing information, Fayuvi’s most common side effects include nausea, vomiting, fever, decreased appetite, elevated liver enzyme levels, low immune cell counts, and low counts of platelets (cell fragments that help blood clot). Following treatment, patients must undergo scheduled monitoring of liver enzymes and platelet counts, as well as monitoring for infusion reactions and allergic reactions.
The FDA’s approval was based on data from the Phase 2/3 TRANSPHER A trial (NCT02716246) and a long-term extension study (NCT04360265). In the TRANSPHER study, 17 children with Sanfilippo A received one-time treatment with Fayuvi at the now-approved dosage of 3.0 × 1013 vector genomes per kg body weight. The average age at treatment was about 22 months, and most patients were followed for more than four years.
Outcomes from these Fayuvi-treated patients were compared against those from 27 patients in a natural history study that tracked outcomes in the absence of treatment. Researchers compared scores on the Bayley-III Cognitive Raw Score, a standardized measure that assesses various cognitive capabilities on a scale from 0 to 91, with higher scores indicating better functioning.
Children treated with Fayuvi in this group had cognitive scores that were 23.5 points higher than those observed in the natural history group. Improvements were generally most pronounced in patients who were treated at younger ages.
Approval is ‘milestone’ for community
“For families living with Sanfilippo syndrome type A, the trajectory of this disease is heartbreaking — children who develop normally in their earliest years facing a relentless regression with no approved treatment to slow it,” said Karim Mikhail, director of the FDA’s Center for Biologics Evaluation and Research. “Parents and clinicians have been waiting far too long for an option.”
Mikhail said FDA approval is a “meaningful step forward — not only for these children and their families, but for the promise of gene therapy to address rare and devastating diseases where the need for safe and effective treatment is the most urgent.”
Advocacy groups cheered the approval. Glenn O’Neill, president and co-founder of the Cure Sanfilippo Foundation, and Terri Klein, president and CEO of the National MPS Society, called it “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.”
“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,” O’Neill and Klein said. “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.”
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