Spruce Biosciences Receives Positive FDA Feedback on TA-ERT for Sanfilippo Syndrome Type B

Spruce Biosciences, Inc. announced the successful completion of Type B meetings with the U.S. Food and Drug Administration regarding its planned biologics license application submission for tralesinidase alfa enzyme replacement therapy (TA-ERT) for the treatment of Sanfilippo syndrome type B (MPS IIIB). The company now anticipates submitting the BLA in the fourth quarter of 2026 to accommodate drug product process performance qualification requirements.

The company held two Type B meetings with the FDA ahead of its anticipated BLA submission for TA-ERT; the first in December 2025 to discuss the company's clinical data and regulatory strategy, and the second in January 2026 to discuss chemistry, manufacturing, and controls (CMC) requirements.

During the December 2025 meeting, the Agency confirmed that the integrated study data from interventional clinical studies of TA-ERT and the available natural history data could potentially serve as an adequate and well-controlled study for purposes of the Agency's review of the effects of TA-ERT on cerebral spinal fluid heparan sulfate non-reducing end (CSF HS-NRE), which could serve as a reasonably likely surrogate endpoint (RLSE) to support an accelerated approval. The Agency also provided recommendations to further support CSF HS-NRE as a RLSE, which the company is incorporating into its planned BLA submission. In addition, Spruce and the Agency discussed the timing and design of a required confirmatory study of TA-ERT, including an agreement to initiate the confirmatory study during BLA review.

Following the January 2026 CMC meeting, the Agency considered the company's plan to address drug product (DP) process performance qualification (PPQ) batch requirements for the BLA submission. In the official meeting minutes, which were received on February 12, 2026, the Agency shared its requirement for one DP PPQ batch at the time of BLA submission and data from a second DP PPQ batch prior to midcycle of BLA review. To accommodate this requirement, the timing of the BLA submission for TA-ERT is now anticipated in the fourth quarter of 2026.

The Chief Executive Officer highlighted the constructive engagement with the agency and noted that the reauthorization of the Rare Pediatric Disease Priority Review Voucher (PRV) program through September 2029 restores a key incentive to develop therapies for rare pediatric diseases, potentially benefiting TA-ERT if approved. The company emphasized that long-term clinical data show reductions in CSF HS-NRE associated with meaningful benefits across cognition, communication, and motor skill acquisition in patients with MPS IIIB, a fatal pediatric neurodegenerative disorder with no approved therapies.

Sanfilippo Syndrome Type B (MPS IIIB) is an ultra-rare, serious, and fatal genetic disease characterized by deficiency in N-Acetyl-Alpha-Glycosaminidase (NAGLU), an enzyme required for the catabolism of heparan sulfate (HS) in lysosomes. It is estimated that MPS IIIB affects fewer than one in 200,000 people in the United States, but the true incidence and prevalence are difficult to ascertain because MPS IIIB is a disease currently not included in newborn screening. The accumulation of toxic levels of cerebral spinal fluid heparan sulfate in the brain is the underlying pathophysiology of MPS IIIB. Although signs and symptoms of MPS IIIB can vary amongst affected individuals, progressive neurodegeneration typically follows a predictable path to brain atrophy, cognitive and developmental impairment, hyperactivity with aggressive and destructive behavior, delayed speech, hearing loss, and motor skill deficits.

The company had a 1-for-75 reverse stock split on July 8, 2025. Stock of Spruce Biosciences, Inc. (SPRB) closed at $58.25 on Tuesday, and traded at $54.79 during Wednesday morning trading, down 5.93 percent over the previous close of $58.24 on the Nasdaq.