Enzyme therapy protects kids’ brain function for up to 6 years

Long-term treatment with the investigational enzyme replacement therapy tralesinidase alfa stabilized cognitive function for up to six years in children with Sanfilippo syndrome type B, clinical trial data showed.

Spruce Biosciences, the therapy’s developer, plans to use the data to support an application seeking accelerated approval of the therapy for Sanfilippo B, with an anticipated submission to U.S. regulators by year’s end.

Trial investigator Nicole Muschol, MD, of the University Medical Center Hamburg-Eppendorf in Germany, presented the findings at the 18th International MPS & Related Lysosomal Diseases Symposium, held June 4-7 in Florence, Italy.

“These long-term findings support the potential of tralesinidase alfa enzyme replacement therapy as the first disease-modifying treatment option for a fatal condition that currently has no approved therapies,” Muschol said in a company press release.

Meanwhile, Spruce is gearing up for a Phase 3 trial (NCT07579910) called TrAnsform, which will evaluate the therapy in 14 children with Sanfilippo type B, ages 1-5.

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Also known as mucopolysaccharidosis type 3 (MPS III), Sanfilippo syndrome is a rare childhood form of dementia in which the body lacks enzymes needed to break down the sugar molecule heparan sulfate. The sugar accumulates in cells and causes damage, especially in the brain. Patients experience progressive neurodegeneration and a range of developmental and behavioral problems that worsen over time.

There are no approved treatments for Sanfilippo type B, a form of the disease in which the affected enzyme is alpha-N-acetylglucosaminidase (NAGLU).

Tralesinidase alfa is an enzyme replacement therapy designed to provide the body with a version of the deficient NAGLU enzyme to help break down heparan sulfate and slow disease progression. It is administered directly into the fluid-filled cavities of the brain in a procedure called intracerebroventricular (ICV) infusion.

A Phase 1/2 clinical trial (NCT02754076) and its extension studies (NCT03784287 and NCT05492799) tested the therapy in 22 children with Sanfilippo type B, ages 2-9, who received infusions every week or every other week. Previous data showed that the therapy helped normalize heparan sulfate levels and slowed declines in cognitive function and brain tissue loss.

The recent presentation covered up to six years of follow-up for the trial participants. Data were compared with findings from external natural history studies that followed outcomes in untreated Sanfilippo B patients.

Tralesinidase alfa led to rapid and sustained normalization of heparan sulfate levels in the spinal fluid. Levels of heparan sulfate non-reducing end, the part of the sugar molecule targeted by NAGLU, were similarly normalized, which is known to correlate with clinical benefits in patients, according to Spruce.

A battery of assessments showed that tralesinidase alfa was associated with stabilization of cognitive function, communication, and motor skills. In the external group of untreated patients, performance on these measures declined over time.

“In a progressive neurodegenerative disease like MPS IIIB, stability itself is a clinically meaningful outcome,” Muschol said.

The volume of cortical gray matter — a type of brain tissue that governs complex cognitive functions, sensory processing, and movement — was also stabilized, compared with an expected decline in the natural course of the disease.

The volumes of the liver and spleen, which can be enlarged in Sanfilippo due to the buildup of sugar molecules, were normalized.

With about 6,000 total doses administered, the treatment’s safety profile was generally consistent with expectations for ICV administration. The most common treatment-emergent side effects were vomiting, fever, and upper respiratory infection.

Data from the study will form the basis of Spruce’s application for accelerated approval of tralesinidase alfa. Accelerated approval allows a therapy to be conditionally marketed based on preliminary evidence that it will be of clinical benefit to patients, in this case, based on the observed normalization of heparan sulfate non-reducing end.

Conversion to full approval requires additional data to establish that benefit. Such confirmatory evidence could be provided by the planned Phase 3 study, which will measure changes in cognition over about five years.