On Friday, July 11, 2025, Ultragenyx Pharmaceutical announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for its Biologics License Application (BLA) for UX111 (ABO-102) AAV gene therapy as a treatment for patients with Sanfilippo syndrome type A (MPS IIIA).
In a letter to the Sanfilippo community co-signed by Ultragenyx Executive Director Heather Lau and Senior Director, Global Patient Advocacy & Engagement, Kristin Voorhees, they stated, “A CRL is a communication from the FDA, indicating that an application cannot be approved in its current form, and is the method that the FDA uses to provide sponsors with the specific observations that need to be addressed for potential approval in the future.”
The letter continued, “In the CRL for UX111, the FDA requested that Ultragenyx provide additional information and improvements related to specific aspects of chemistry, manufacturing and controls (CMC) and observations from the recently completed manufacturing inspections. It’s important to know that we believe that the FDA observations are readily addressable and we have already addressed many of them. The FDA observations are related to facilities and processes and are not directly related to the quality of the product [UX111]. The CRL did not note any review issues related to the clinical data package nor clinical inspections.”
“Our goal is to get UX111 to patients as quickly as possible knowing how critical this first therapy is to the Sanfilippo community. We have been diligently responding to the recent CMC observations and our priority is to resolve them so that we can resubmit the BLA as soon as possible,” said Ultragenyx Chief Executive Officer and President Emil D. Kakkis, MD, PhD, in a July 11 press release. “We believe the CMC observations are readily addressable and many have already been addressed. While the CRL will delay the potential approval of UX111 to 2026, we are working with urgency to respond and resubmit.”
The press release also stated, Ultragenyx “will be working with the FDA over the next few months to resolve the observations. Once resolution is achieved, the company expects to resubmit the BLA and anticipates up to a 6-month review period to follow the resubmission.”
Cure Sanfilippo Foundation understand that these requests by the FDA are not directly related to the quality of the gene therapy product. They also do not affect the ongoing screening, enrollment and delivery of gene therapy to children who are or will be participating in cohort 4 of the current clinical trial. This provides further confidence that the gene therapy drug is safe for use in patients in clinical trial.
It is also important to recognize that FDA’s requests are NOT centered around inspections of the clinical study sites or how children are responding to treatment in the trial, including the vast amount of safety and efficacy data gathered from children who have received UX111 in clinical trial over the past 9 years.
The team at Ultragenyx has been and continues to work urgently to address all requests by the FDA. They will next be working to prepare the resubmission of its biologics license application (BLA ) for approval. Because UX111 has received a priority review designation, when the BLA is resubmitted, FDA would aim to complete its review within a 6 month timeframe from the date of resubmission.
Cure Sanfilippo Foundation intimately understand the critical nature of time in this disease process and how any delay in treatment causes direct harm to children with Sanfilippo. Cure Sanfilippo Foundation remains in active communication with Ultragenyx and is working with our community advocacy partners, families and you, our community of supporters, to ensure that the FDA has a clear understanding of the negative impact of such a delay upon children’s lives and the need for a swift and efficient review when Ultragenyx resubmits its application.
Read more about the UX111 gene therapy, including its history and clinical trial information.