Spruce to move tralesinidase alfa into Phase 3 clinical study
Company to file biologics license application in 2026 1st half
Spruce Biosciences said it plans to launch a Phase 3 clinical study of tralesinidase alfa as an enzyme replacement therapy for children with Sanfilippo syndrome type B, a move toward seeking accelerated approval of the treatment.
The company said it plans to file a biologics license application (BLA) in the first half of next year.
Spruce acquired the rights to tralesinidase alfa, also known as TA-ERT or AX 250, after the previous developer, Allievex, ended its clinical program for Sanfilippo syndrome type B. Allievex had originally licensed the experimental enzyme replacement therapy from Biomarin Pharmaceutical.
“This is truly a transformative moment for Spruce as we focus our expertise in rare disease on a potential near-term commercial opportunity with TA-ERT in [Sanfilippo syndrome type B],” Javier Szwarcberg, MD, Spruce’s CEO, said in a company press release.
Because there are no approved therapies for Sanfilippo syndrome type B, “this new strategy opens a new chapter in our mission to provide transformative and life-changing therapies to patients affected by serious conditions with significant unmet medical need,” Szwarcberg said.
Lab-made version of enzyme
In Sanfilippo syndrome type B, genetic mutations lead to little or no activity of an enzyme called alpha-N-acetylglucosaminidase, or NAGLU. This enzyme helps break down a complex molecule called heparan sulfate. Without it, partially broken-down heparan sulfate builds up to toxic levels in the body.
As with other types of Sanfilippo syndrome, this buildup mainly damages the brain and spinal cord. Sanfilippo symptoms usually begin in early childhood and become more severe over time. Children may have delays in development, challenges in behavior, and difficulties with learning and everyday activities.
Tralesinidase alfa is designed to supply the body with a lab-made, functional version of the NAGLU enzyme. It’s delivered directly into the fluid around the brain and spinal cord, called the cerebrospinal fluid (CSF), through an infusion into the brain’s fluid-filled cavities using a small device implanted in the skull.
Preclinical studies in non-human primates showed that tralesinidase alfa was evenly distributed throughout the brain and well tolerated regardless of the dose infused. In an animal model of Sanfilippo syndrome type B, dogs treated with tralesinidase alfa performed better on cognitive tests than those on a placebo.
In a completed Phase 1/2 clinical study (NCT02754076) with 22 children, ages 2–9, diagnosed with Sanfilippo syndrome type B, 300 mg of tralesinidase alfa — infused weekly for nearly one year, and weekly or every other week thereafter for up to five years — normalized the levels of heparan sulfate and heparan sulfate with a non-reducing end (NRE) in the CSF. The NRE is the end of the molecule that is free to interact with other molecules, and the target of the NAGLU enzyme.
Treatment also slowed the loss of brain volume and cognitive function.
“In clinical studies, TA-ERT has been shown to significantly and durably normalize [heparan sulfate-NRE levels in the CSF] over a five-year period,” Szwarcberg said. “Based on the existing clinical and non-clinical data, we anticipate submitting a BLA for TA-ERT to the [U.S. Food and Drug Administration (FDA)] in the first half of 2026.”
In a meeting last year, the FDA agreed with the use of HS-NRE as a biomarker that could support an accelerated approval. The regulator also agreed with the company’s design for a five-year, confirmatory Phase 3 clinical study that plans to enroll an estimated 14 children with Sanfilippo syndrome type B.
“[HS-NRE] can be used as a biomarker that may reasonably predict clinical benefit and as the primary endpoint for the BLA accelerated approval submission,” Kirk Ways, MD, PhD, Spruce’s chief medical officer, said during an April webcast announcing the company’s plans for tralesinidase alfa.
Confirmatory data would be needed for full approval. The main goal of the Phase 3 clinical study, planned to launch in the first half of next year, will be to watch for differences in the Bayley’s Cognition Raw Score, a measure of early delays in development, between children on tralesinidase alfa and those on a placebo.
If the BLA is approved, Spruce said, it will build a targeted team to support the launch of tralesinidase alfa. Since most patients are treated by a small group of specialists, the company believes it can serve this market with a focused team and personalized patient support programs.
“The vision of the Spruce leadership team and their unrelenting commitment to serving patient communities with meaningful unmet need is on full display with the acquisition of TA-ERT,” said Mike Grey, Spruce’s executive chairman.
About the Author
