Tralesinidase alfa ERT for Sanfilippo type B children put on fast track
FDA's breakthrough therapy designation aimed at speeding up development
Tralesinidase alfa, also known as TA-ERT, Spruce Biosciences’ investigational enzyme replacement therapy (ERT) for children with Sanfilippo syndrome type B, has received breakthrough therapy designation from the U.S. Food and Drug Administration (FDA).
The designation is intended to speed up the development and review of treatments that show early evidence of meaningful improvements over existing treatments for serious or life-threatening diseases. It provides enhanced FDA guidance and support throughout development, allows for the rolling submission of application materials, and makes therapy eligible for priority review — all measures aimed at bringing promising treatments to patients sooner.
The company plans to file a biologics license application (BLA) — a formal request for FDA approval to market a biologic therapy — in the first months of next year. It will seek accelerated approval based on existing clinical data, while confirmatory evidence for full approval will come from a planned Phase 3 trial.
“We are pleased to receive U.S. FDA Breakthrough Therapy Designation as we prepare to submit the Biologics License Application of TA-ERT for the treatment of [Sanfilippo syndrome type B] in the first quarter of 2026,” Javier Szwarcberg, MD, Spruce’s CEO, said in a company press release. “This designation highlights TA-ERT’s potentially transformative clinical impact as the first disease-modifying therapy to treat [Sanfilippo syndrome type B] in children impacted by this devastating condition.”
Tralesinidase alfa designed to deliver lab-made version of missing enzyme
Sanfilippo syndrome type B is caused by the absence or reduced activity of the alpha-N-acetylglucosaminidase (NAGLU) enzyme due to mutations in the NAGLU gene. Without it, the body cannot properly break down a complex sugar molecule called heparan sulfate.
As heparan sulfate accumulates to toxic levels inside cells, it causes progressive damage — particularly in the central nervous system, or the brain and spinal cord — leading to the hallmark Sanfilippo symptoms. These typically begin in early childhood and include developmental delays, behavioral issues, sleep disturbances, and progressive loss of cognitive and motor abilities, which worsen over time. Currently, there are no approved therapies for Sanfilippo syndrome type B.
Tralesinidase alfa is designed to deliver a lab-made, or recombinant, version of the missing enzyme, thereby restoring the body’s ability to break down heparan sulfate. The therapy is infused directly into the cerebrospinal fluid (CSF), the liquid that surrounds the brain and spinal cord, through an injection into one of the brain’s four CSF-filled cavities using a small device implanted in the skull.
Originally developed by BioMarin Pharmaceutical, the experimental ERT was later licensed to Allievex, which ended its Sanfilippo syndrome type B clinical program before Spruce acquired the rights to tralesinidase alfa.
Trials showed treatment lowered accumulation of heparan sulfate
Building on promising preclinical studies in animal models, tralesinidase alfa has been tested in a Phase 1/2 clinical study (NCT02754076), called BMN 250-201, and two open-label extension studies, NCT03784287 and NCT05492799.
These trials enrolled a total of 22 children, ages 2 to 9, with Sanfilippo syndrome type B who received 300 mg of tralesinidase alfa every week or every other week, for up to five years.
Results from the Phase 1/2 trials showed that treatment lowered the accumulation of heparan sulfate and heparan sulfate non-reducing end (HS-NRE) — the portion of the molecule normally targeted by the NAGLU enzyme — in the CSF. This was accompanied by stabilization of cortical gray matter volume — the outer layer of the brain that contains most neuron cell bodies — and by maintenance or slower decline in cognitive function compared with the progressive decline typically seen in untreated children.
The integrated group-level clinical data demonstrates a rapid, profound, and durable effect of TA-ERT in normalizing CSF HS-NRE, the pathogenic [disease-causing] factor leading to neurodegeneration, and stabilizing cortical grey matter volume and cognitive function in children with [Sanfilippo syndrome type B].
In the long-term extension studies, where children continued therapy for up to five years, these benefits were maintained over time. According to integrated long-term clinical data, the results confirmed and extended earlier findings, showing a durable lowering of HS-NRE, as well as sustained stabilization of brain volume and cognitive function.
“The integrated group-level clinical data demonstrates a rapid, profound, and durable effect of TA-ERT in normalizing CSF HS-NRE, the pathogenic [disease-causing] factor leading to neurodegeneration, and stabilizing cortical grey matter volume and cognitive function in children with [Sanfilippo syndrome type B],” Szwarcberg said.
These data will form the basis of Spruce’s BLA filing to the FDA. In a meeting last year, the agency agreed that HS-NRE could serve as a biomarker reasonably likely to predict clinical benefit, supporting a submission under the accelerated approval pathway.
As part of the company’s plan to confirm the therapy’s benefit for full approval, a five-year Phase 3 clinical trial is expected to begin in the first half of next year and enroll about 14 children with Sanfilippo syndrome type B. The study will evaluate tralesinidase alfa against a placebo and will primarily measure changes in the Bayley’s Cognition Raw Score, which assesses early cognitive development in young children.
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