Spruce Biosciences Reports Six-Year Data Showing Tralesinidase Alfa Preserves Cognitive Function in Sanfilippo Syndrome Type B
核心洞察
Spruce Biosciences presented six-year data at the 22nd Annual WORLDSymposium demonstrating that tralesinidase alfa enzyme replacement therapy (TA-ERT (搜索)) rapidly normalized cerebrospinal fluid heparan sulfate levels and preserved cognitive function in 22 patients with Sanfilippo Syndrome Type B (搜索).
The treatment stabilized cognitive, communication, and motor skills over six years compared to natural history patients, with approximately 6,000 doses administered showing a consistent safety profile.
A sibling comparison study revealed that the treated child maintained higher cognitive and functional abilities at age 12.1 years compared to an untreated sibling at age 11.7 years.
Spruce Biosciences announced compelling six-year data for tralesinidase alfa enzyme replacement therapy (TA-ERT (搜索)) in patients with Sanfilippo Syndrome Type B (搜索) (MPS IIIB (搜索)), positioning the treatment as a potential first disease-modifying therapy for this fatal genetic disorder. The data, presented at the 22nd Annual WORLDSymposium, demonstrated sustained preservation of cognitive and functional abilities in treated patients compared to natural history controls.
Long-Term Efficacy Demonstrates Disease Modification
In an analysis of 22 patients enrolled in interventional studies and followed for up to six years, TA-ERT (搜索) treatment achieved rapid and durable normalization of cerebrospinal fluid heparan sulfate non-reducing end (CSF HS-NRE), a surrogate endpoint reasonably likely to predict clinical benefit in patients with MPS IIIB (搜索). The treatment stabilized cognitive function as assessed by the Bayley-III Cognitive Raw Score relative to declines observed in untreated natural history patients.
"This long-term data supports tralesinidase alfa enzyme replacement therapy as potentially the first disease-modifying treatment option for individuals living with Sanfilippo Syndrome Type B (搜索), a fatal condition for which no approved therapies currently exist," said Nicole Muschol, M.D., from the International Center for Lysosomal Disorders at the University Medical Center Hamburg-Eppendorf in Germany and Principal Investigator.
The treatment also stabilized cortical gray matter volume, which declined in untreated natural history patients, and normalized liver and spleen volume. Analysis using the validated Vineland Adaptive Behavior Scales showed that TA-ERT (搜索) stabilized receptive and expressive communication, as well as fine and gross motor skills, compared to decline in these outcomes in untreated patients.
Sibling Comparison Reveals Functional Preservation
A second analysis examined two siblings diagnosed with non-attenuated, severe MPS IIIB (搜索), with one receiving TA-ERT (搜索) treatment and the other remaining untreated. The age-matched comparison revealed striking differences in functional outcomes. At 12.1 years of age and one month after cessation of treatment, the sibling treated with TA-ERT could speak a few words, was toilet trained, and could feed himself finger foods. In contrast, the untreated sibling at age 11.7 years was nonverbal, no longer toilet trained, and dependent on caregivers for feeding.
"When we compare clinical observations at a similar age range between the treated and untreated siblings, we see a clear divergence in cognitive and functional ability, demonstrating the potential of TA-ERT (搜索) to be a novel and clinically meaningful treatment option for children and families impacted by MPS IIIB (搜索)," said Irene Chang, M.D., Associate Professor at the University of California, San Francisco.
Safety Profile Supports Long-Term Administration
Over the six-year study period, approximately 6,000 doses were administered to 22 patients with a safety profile consistent with intracerebroventricular administration. The treatment was generally well-tolerated across the extended treatment duration.
"Seeing sustained normalization of CSF HS-NRE alongside long-term stabilization of cognitive function, communication, and motor skills strengthens our confidence in the potential of TA-ERT (搜索)," said Kirk Ways, M.D., Ph.D., Chief Medical Officer of Spruce Biosciences.
Addressing Critical Unmet Medical Need
Sanfilippo Syndrome Type B (搜索) is an ultra-rare, fatal genetic disease affecting fewer than one in 200,000 people in the United States. The condition is characterized by deficiency in N-Acetyl-Alpha-Glycosaminidase (搜索) (NAGLU (搜索)), leading to toxic accumulation of heparan sulfate in the brain. Progressive neurodegeneration typically results in cognitive impairment, behavioral changes, motor skill deficits, and ultimately death, with estimated life expectancy ranging from 15 to 19 years of age.
TA-ERT (搜索) is a fusion protein comprised of recombinant human alpha-N-acetylglucosaminidase fused to an insulin-like growth factor 2 peptide, enabling cellular uptake and lysosomal delivery. The therapy is administered via intracerebroventricular injection to restore enzyme activity in the central nervous system.
The company plans to advance the program through a biologics license application submission and potential FDA approval, representing hope for families affected by this devastating disorder where currently no approved therapies exist.