Ultragenyx Pharmaceutical has received a complete response letter (CRL) from the US Food and Drug Administration (FDA) concerning its biologics licence application (BLA) for UX111 (ABO-102), an adeno-associated virus (AAV) gene therapy aimed at treating Sanfilippo syndrome type A (MPS IIIA).

MPS IIIA is a rare and fatal lysosomal storage disorder that primarily impacts the brain and currently has no approved treatments.

This decision requires the company to submit further details, particularly in areas related to chemistry, manufacturing and controls (CMC).

The FDA's request stems from observations during recent inspections of Ultragenyx's manufacturing facilities.

The company is confident that these concerns, which pertain to facilities and processes rather than product quality, can be promptly addressed. Efforts are underway to work with the FDA to resolve them.

Once this is done, Ultragenyx plans to resubmit the BLA and then anticipates a review period of up to six months. Despite this setback in manufacturing-related aspects, clinical reviews have been positive.

Ultragenyx CEO and president Emil Kakkis stated: “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.

“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 FDA has recognised that the neurodevelopmental outcome data presented so far are robust. Biomarker data have also been acknowledged as providing supportive evidence.

Notably absent from the CRL were any concerns about clinical data or inspection outcomes. Updated clinical data from ongoing patient treatments will need inclusion in the revised submission.