What the Ultragenyx plans for Accelerated Approval filing announcement mean for Sanfilippo

June 19, 2024

On June 12, the milestone news was announced that Ultragenyx Pharmaceutical Inc. held a successful meeting with the U.S. Food and Drug Administration (FDA), during which they reached an agreement that cerebral spinal fluid heparan sulfate is a reasonable surrogate endpoint that could support submission of a biologics license application (BLA) seeking accelerated approval for UX111 (ABO-102) AAV gene therapy for the treatment of Sanfilippo syndrome (MPS IIIA).

Ultragenyx also announced its plans to file for Accelerated Approval of UX 111 in late 2024 or early 2025, after further discussion with the FDA. In the announcement, Ultragenyx said that it believes, “the door is now open for cerebral spinal fluid heparan sulfate to be used as a relevant biomarker to support new treatments for all fatal neuronopathic types of MPS.”

This major milestone in FDA decision-making comes on the heels of the February 2024 workshop hosted by the Reagan Udall Foundation regarding “Developing Biomarkers to Support Accelerated Approval in Rare Diseases.” The Foundation was among the organizations and industry experts urging the FDA to recognize the scientific relevance and utility of cerebrospinal fluid heparan sulfate, as a primary biomarker to support accelerated approval in the neuronopathic MPS disorders. Cure Sanfilippo was honored to be able to give the 10-minute closing remarks on this topic during this meeting, sharing the patient perspective.

Cure Sanfilippo Foundation’s donors provided a significant early investment in the development of this treatment, through the initial sponsor Abeona Therapeutics and academic study site in the US, along with many other co-funding organizations in the community. While drug development never moves as fast as this disease necessitates, we celebrate the important progress that has been made over the past decade and this ‘interim win’ for our community. Since this press release mentions only the FDA, this is applicable for the United States. However, other countries and regions have their own regulatory agencies and we will be watching closely for updates from Ultragenyx regarding other areas around the world.

Frequently-Asked Questions

The following are some questions that many in the Sanfilippo community have following the Ultragenyx announcement.

What does Accelerated Approval mean?

Accelerated approval refers to a regulatory pathway of the FDA that allows drugs for serious conditions, which are intended to fill an unmet medical need, to be approved based on a surrogate endpoint (in our case, measurement of heparan sulfate levels in the cerebrospinal fluid). This pathway is typically faster in obtaining the necessary data from clinical trials than the traditional approval pathway based on clinical endpoints (how a person feels, functions or survives). Read more about Accelerated Approval on the FDA website.

What does this mean for individuals living with Sanfilippo type A today?

While this is a milestone step forward in the path to developing treatments for Sanfilippo, there is still much work to be done for a treatment to be approved and reach those in need. Ultragenyx will continue to be in discussion with the FDA around its planned BLA submission, which it says they hope to submit in late 2024 or early 2025. After submission of the BLA, typical timelines for the FDA to consider whether they will approve a drug or not are around 10 months (however, we do not know the exact timelines). Even after approval of a drug, it can take time for the treatment to be accessed by patients. These timelines are not clear at this time. However, Cure Sanfilippo Foundation continues to be in close collaboration and communication with Ultragenyx around the need for the broadest access to this potential treatment for the community as quickly as possible.

What does this mean for individuals living with other forms of Sanfilippo (types B, C, or D)?

FDA acceptance of cerebral spinal fluid heparan sulfate as a surrogate biomarker for the UX 111 gene therapy is an important first step. While the FDA considers every treatment under development on an individual basis, the most up-to-date science supports the usefulness of cerebral spinal fluid heparan sulfate as a surrogate biomarker across the many forms of MPS that have neurological damage [MPS I, MPS II, MPS III (all forms of Sanfilippo), and MPS VII]. The use of cerebral spinal fluid heparan sulfate as a biomarker is most relevant to therapies that are designed to restore enzyme function and/or reduce heparan sulfate accumulation in the central nervous system. We hope that FDA recognition of this biomarker will pave the way for more efficient drug development for all Sanfilippo subtypes and most urgently for those treatments that are also in clinical trial both in the US and beyond.

While hopeful progress is being made, there is still a great deal of work ahead to help all of the children in need. Cure Sanfilippo Foundation will continue to support advances in research for all forms of Sanfilippo syndrome by providing funding support for scientific discovery and clinical trials, collaboration and design support of clinical programs, advocacy to ensure the perspectives and needs of the community are integrated into drug development, and the convening of experts and families.

To read the complete announcement and next steps, read the letter from Ultragenyx.

This is a very exciting time for the Sanfilippo and the wider MPS community. We will continue to keep you updated as additional information becomes available. If you have any questions, please reach out and we will do our best to get answers. Email us anytime at Contact@CureSanfilippoFoundation.org

Learn more about the UX111 (ABO-102) AAV gene therapy program for the treatment of Sanfilippo syndrome.

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