Spruce Biosciences Receives FDA Breakthrough Therapy Designation for Tralesinidase Alfa for Sanfilippo Syndrome Type B

Spruce Biosciences received Breakthrough Therapy Designation from the FDA for tralesinidase alfa enzyme replacement therapy (TA-ERT) for the treatment...

Breakthrough Clinical Results

Spruce Biosciences received Breakthrough Therapy Designation from the FDA for tralesinidase alfa enzyme replacement therapy (TA-ERT) for the treatment of Sanfilippo Syndrome Type B (MPS IIIB). The designation is supported by clinical data demonstrating normalization in cerebral spinal fluid Heparan Sulfate Non-Reducing End (CSF HS-NRE). The company plans to submit the Biologics License Application of TA-ERT for MPS IIIB in the first quarter of 2026. TA-ERT is a fusion protein comprised of recombinant human alpha-N-acetylglucosaminidase (rhNAGLU) intended as an enzyme replacement therapy for patients with MPS IIIB.

Key Highlights

FDA grants Breakthrough Therapy Designation to tralesinidase alfa (TA-ERT) for Sanfilippo Syndrome Type B (MPS IIIB).
Clinical data shows normalization of CSF HS-NRE with TA-ERT treatment.
TA-ERT is a potential disease-modifying therapy for MPS IIIB in children.
Biologics License Application submission for TA-ERT is planned for Q1 2026.

Incidence and Prevalence

Latest Estimates of Sanfilippo Syndrome Incidence and Prevalence Globally

Global Prevalence

According to a 2020 meta-analysis, the pooled global birth prevalence of Sanfilippo syndrome (mucopolysaccharidosis [MPS] III) was estimated at 0.76 cases per 100,000 live births (95% CI: 0.57-0.96). This rare autosomal recessive lysosomal storage disorder has four subtypes (A, B, C, and D).

A 2019 systematic review found that the lifetime risk at birth for all four subtypes combined ranges from 0.17-2.35 per 100,000 live births.

Prevalence by Subtype

The prevalence by subtype according to the 2020 meta-analysis was:

MPS IIIA: 0.52 cases per 100,000 live births (95% CI: 0.33-0.72)
MPS IIIB: 0.21 cases per 100,000 live births (95% CI: 0.12-0.30)
MPS IIIC: 0.01 cases per 100,000 live births (95% CI: 0.005-0.02)

The most prevalent subtypes worldwide are A and B, followed by C and D subtypes.

Estimated Patient Population

Based on the global population size (7.8 billion) and the life span of patients, researchers estimated there would be approximately 12-19 thousand Sanfilippo syndrome patients worldwide as of 2020.

Regional Variations

A 2022 study in Egypt found that among diagnosed MPS cases, 31% were MPS type III, making Sanfilippo the most common MPS type among referred cases to their Biochemical Genetics Department. In this Egyptian cohort, MPS IIIB was found in 49.3% of patients, while MPS IIIA accounted for 20.6%. The remaining 30.1% were either Sanfilippo type C or D.

A 1995 study in Greece found that Sanfilippo B was the most frequent type III MPS and also the most frequent MPS identified in their study, accounting for 17.0% of all diagnosed lysosomal disorders.

Historical data shows the incidence of Sanfilippo syndrome was estimated at 1:24,000 in The Netherlands with MPS IIIA being the most common subtype.

There is a particularly high incidence of a clinically severe form of MPS-IIIA in the Cayman Islands with a carrier frequency of 0.1.

In a 2023 Turkish study, researchers noted that due to the high rate of consanguinity in Turkey, the incidence of Sanfilippo syndrome might be higher compared to other populations worldwide.

Context Within MPS Disorders

Mucopolysaccharidoses (MPS) as a group have a relatively frequent overall incidence of approximately 1 in 20,000-25,000 births.

Diagnostic Challenges

Due to mild somatic disease compared to other MPS disorders, there is difficulty in diagnosing mild cases of MPS-III. Hence, Sanfilippo syndrome may be underdiagnosed, especially in patients with mild mental retardation.

Researchers note that higher-quality epidemiological data are needed to appropriately target resources for disease research and management of this exceptionally rare but devastating condition affecting children.

Key Unmet Needs for Sanfilippo Syndrome

Treatment Needs

Sanfilippo syndrome remains a severe life-limiting disease with no approved treatments despite numerous research efforts. Several therapeutic approaches under development include enzyme replacement therapy (ERT), substrate reduction therapy (SRT), and gene therapy, while stem cell approaches remain pre-clinical. Although animal models show promise, clinical trials have proven costly with limited therapeutic effects. Notably, treatments demonstrate therapeutic benefit when applied pre-symptomatically in early-diagnosed children.

Diagnostic and Biomarker Needs

Newborn screening represents a critical unmet need to enable pre-symptomatic diagnosis and optimal therapeutic outcomes. Currently, there are no tools or laboratory-based biomarkers available for pre-symptomatic prognosis or to stratify which Sanfilippo infants will need treatment in toddlerhood. The field lacks progression and neurocognitive response-to-treatment biomarkers, making robust blood-based biomarkers an urgent necessity. Promising candidates include neural-derived exosomes from blood to detect synaptic protein and mitochondrial function changes, glial fibrillary acidic protein in plasma/serum, and neurofilament light chain for measuring active brain atrophy.

Symptom Management Needs

Caregivers identify communication and mobility as domains with highest unmet treatment needs, followed closely by pain and sleep. Other impactful areas include eating, adaptive skills, and behaviors. Parents report high caregiving burden across all disease stages, with multiple domains affecting child and family quality of life, including cognitive-behavioral challenges and physical health symptoms. Even modest treatment benefits are highly valued by caregivers, with most parents willing to "try anything," including high-risk treatments.

Patient Populations Being Targeted

Recent clinical trials have targeted various patient populations: * Children with Sanfilippo syndrome aged 2-24 years with varying disease progression * MPS IIIB (Type-B) patients, who represent approximately one-third of all Sanfilippo cases * Patients with early disease before behavioral manifestations appear, using ophthalmological evaluations as diagnostic indicators * Children diagnosed through known familial inheritance risk

Clinical Care Guidelines

There are no published standard global clinical care guidelines for Sanfilippo syndrome patients. Best practice guidelines are critical for prompt diagnosis and appropriate care initiation. International efforts are underway to create consensus clinical guidelines accessible to clinicians globally and provide practical resources for families to share with local care teams inexperienced with this rare disease.

Emerging Therapeutic Approaches

Adeno-associated virus (AAV) gene therapy shows promise, with the triple-capsid mutant AAV8 (TCM8) demonstrating superior transgene expression in Sanfilippo mouse models compared to both AAV5 and AAV9 when delivered to the central nervous system.

Company drugs in pipeline

Spruce Biosciences Drug Pipeline Indications

I don't have specific information about Spruce Biosciences or its drug pipeline in my knowledge base. To provide accurate information about which indications Spruce Biosciences has drugs in development for, including their clinical trial phases and targeted conditions, I would need to reference their official company materials, recent press releases, or clinical trial registries.

For the most current and accurate information about Spruce Biosciences' pharmaceutical pipeline, I recommend:

Visiting the official Spruce Biosciences website, particularly their pipeline or research and development sections
Checking clinical trial registries like ClinicalTrials.gov
Reviewing recent investor presentations or SEC filings
Examining press releases from the company regarding their drug development programs

These sources would provide comprehensive details about their drug candidates, the specific conditions they aim to treat, and the current stages of development for each product in their pipeline.