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Clinical Trial Summary
Study: Intracerebroventricular Tralesinidase Alfa in Children With Mucopolysaccharidosis Type IIIB (TrAnsform)
Trial Listing: Read this clinical trial’s information on ClinicalTrials.gov, for more details including contact information to reach out to the study sites, full inclusion and exclusion criteria. We encourage you to check the Clinicaltrials.gov link frequently for updates on possible new study sites and changes in enrollment status or criteria.
Study status: Not Yet Recruiting
Study Information: MPS3BStudy.com. The website provides information about TA-ERT, the planned Expanded Access Program and the TrAnsform confirmatory study. Families can also register their interest at the MPS3BStudy.com website to receive updates as sites activate and enrollment begins.
Route of administration: intracerebroventricular (ICV) into the fluid space of the brain
Frequency of administration: Infusion once weekly
Length of program: 5 years (roughly 260 weeks)
Anticipated number of participants: TBA
Inclusion criteria:
- A confirmed diagnosis of MPS IIIB;
- Between 1 and 5 years old at the start of the study;
- Have a BSID-II-C score less than 70;
- A parent or legal guardian gives written permission for them to take part; and
- The family or care partner can come to regularly required study visits and follow the study plan
Exclusion criteria:
- A health condition that makes the study’s surgical procedure deemed risky for them;
- Seizures that are not well-controlled;
- Taking part in another research study with an investigational drug; and
- There is another reason the doctor feels the study is not a good fit for them
Trial Information
Tralesinidase Alfa Enzyme Replacement Therapy (TA-ERT), formerly AX250 and BMN 250, is an enzyme replacement therapy for Sanfilippo syndrome type B. This drug product is a fusion protein consisting of NAGLU (Sanfilippo B enzyme) fused with IGF-2. This modification is intended to improve NAGLU enzyme uptake into cells.
Tralesinidase alfa (BMN 250) was originally developed by BioMarin Pharmaceuticals. In 2019, Allievex Corporation obtained an exclusive worldwide license for the therapy, then known as AX250, from BioMarin. In 2024, Spruce Biosciences acquired the program from Allievex, renaming it tralesinidase alfa enzyme replacement therapy (TA-ERT).
This experimental therapy is delivered weekly into the cerebrospinal fluid (CSF) through an intracerebroventricular (ICV) reservoir (i.e. Ommaya reservoir). Based on clinical data, it has been proposed that after CSF-heparan sulfate levels are normalized, treatment may be spaced to every other week.
In an earlier Phase 1/2 clinical trial of tralesinidase alfa, the study’s primary objective was to evaluate safety and tolerability as well as preliminary efficacy on cognitive function. This study consisted of two parts. Part 1 was a dose escalation period involving 3 patients. Part 1 patients rolled over to Part 2 in which the optimal dose (300mg) was then given to all patients. Nineteen additional patients enrolled in a 1 year observational study (study 901) and then transitioned over to Part 2 of the treatment trial. At the time of study closure in October 2023, a handful of patients remained in the study and continued receiving remaining drug product under expanded access until drug supply was exhausted.
Promising study results have been published in a peer reviewed manuscript and in press releases in the Program Updates sections below.
Note: Spruce is also conducting an Early Access Program (EAP) providing a way for some participants with MPS IIIB to receive the investigational treatment outside of the TrAnsform Study. Learn more about the Expanded Access Program.
Program Updates
September 2026
Spruce announces the launch of MPS3BStudy.com, a single website where families and caregivers can learn about the planned EAP and TrAnsform confirmatory study and also register interest in both. Additionally, in the letter, Szwarcberg states, “Spruce expects to initiate both the EAP and the TrAnsform confirmatory study as early as the fourth quarter of 2026.” Read the complete letter.
August 2026
Spruce Biosciences announced on Aug. 26, 2026, that it has completed two pre-BLA (Biologics License Application) meetings with the U.S. Food and Drug Administration (FDA) in support of its plan to submit its BLA in fourth quarter 2026 for tralesinidase alfa enzyme replacement therapy (TA-ERT) for the treatment of Sanfilippo Syndrome Type B. Read statement from Spruce.
June 2026
Spruce Biosciences shared long-term data from its tralesinidase alfa enzyme replacement therapy (TA-ERT), an investigational treatment for Sanfilippo Syndrome type B (MPS IIIB), at the 18th International MPS & Related Lysosomal Diseases Symposium, June 4-7, 2026, in Florence, Italy.Read more.
May 14, 2026
Spruce announced continued progress toward BLA submission for TA-ERT for the treatment of MPS IIIB, detailing the following in a press release:
- Spruce continues to advance manufacturing readiness, regulatory interactions, and commercial planning to support an anticipated BLA submission in the fourth quarter of 2026.
- Spruce continues to advance plans for a confirmatory study in patients with MPS IIIB and expanded access program to support continued patient access prior to and following potential approval.
- To prepare for a potential U.S. commercial launch of TA-ERT, if approved, Spruce has built out its rare disease commercial organization with three senior appointments.
May 1, 2026
Spruce Biosciences has announced that it is currently planning for an Expanded Access Program (EAP) in the United States to its investigational product, TA-ERT, for a limited number of MPS IIIB patients through an EAP protocol. More information may be found at ClinicalTrials.gov when available and by contacting us at EA@sprucebio.com.
February 18, 2026
Spruce Biosciences announced the successful completion of Type B meetings with the U.S. Food and Drug Administration (FDA or the Agency) regarding its planned upcoming biologics license application (BLA) submission for tralesinidase alfa enzyme replacement therapy (TA-ERT).
The company held two Type B meetings with the FDA ahead of its anticipated BLA submission for TA-ERT; the first in December 2025 to discuss the company’s clinical data and regulatory strategy, and the second in January 2026 to discuss chemistry, manufacturing, and controls (CMC) requirements. Read more.
February 5, 2026
Spruce Biosciences announced at the 22nd Annual WORLDSymposium™ that data from two different analyses presented today demonstrate that the long-term administration of tralesinidase alfa enzyme replacement therapy (TA-ERT) resulted in rapid and durable reduction of heparan sulfate and preserved cognitive and non-cognitive outcomes in patients with Sanfilippo Syndrome Type B (MPS IIIB) relative to natural history patients. Read the statement from Spruce.
In an analysis of 22 patients who enrolled in interventional studies of TA-ERT and followed up to six years, Spruce shared that TA-ERT treatment:
- Rapidly and durably normalized levels of cerebral spinal fluid heparan sulfate non-reducing end (CSF HS-NRE), a surrogate endpoint reasonably likely to predict clinical benefit in patients with MPS IIIB;
- Stabilized cognitive function as assessed by Bayley-III Cognitive Raw Score (BSID-C), the cognitive subscale of the validated Bayley Scales of Infant and Toddler Development – Third Edition (Bayley-III) scale relative to declines seen in untreated natural history patients;
- Stabilized cortical gray matter volume, which declined in untreated natural history patients, and normalized liver and spleen volume; and
- Was generally consistent with the safety profile of intracerebroventricular (ICV) administration; over the six-year study, approximately 6,000 doses were administered to 22 patients.
January 2026
Spruce Biosciences announced that as of January 7, 2026, it has entered into a loan facility with Avenue Venture Opportunities Fund II, L.P., a fund of Avenue Capital Group (Avenue Capital), for up to $50 million in growth capital. “The loan facility has a 42-month term and includes an initial tranche of $15 million, which will be fully funded on or around January 9, 2026, and three additional tranches totaling up to $35 million, the funding of which is subject to the satisfaction of certain terms and conditions of the loan and security agreement, including the achievement of key regulatory and commercial milestones related to the company’s development and planned commercial launch of tralesinidase alfa enzyme replacement therapy (TA-ERT) for the treatment of Sanfillipo Syndrome Type B (MPS IIIB),” per Spruce’s press release. Read the entire press release.
November 2025
Spruce Biosciences reported financial results for the third quarter ended September 30, 2025, and provided the following corporate updates. Read the press release.
- Syndication of a $50 million private placement financing backed by an impressive group of healthcare investors
- Significant progress this year with the receipt of Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for TA-ERT
- Biologics license application (BLA) submission to FDA expected in first quarter 2026
October 2025
U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to Spruce’s tralesinidase alfa enzyme replacement therapy (TA-ERT) for the treatment of Sanfilippo Syndrome Type B (MPS IIIB). In a press statement, Spruce said it plans to submit the Biologics License Application of TA-ERT for the treatment of MPS IIIB to FDA for approval in first quarter 2026. Read the press release.
August 2025
Spruce Biosciences announced that integrated long-term clinical data of TA-ERT demonstrated profound and durable efficacy and safety in patients with Sanfilippo Syndrome Type B (MPS IIIB). Spruce reported that TA-ERT “profoundly and durably lowered cerebral spinal fluid heparan sulfate non-reducing end, the factor responsible for neurodegeneration in MPS IIIB.” Additionally, cognition and cortical grey matter volume were stabilized in patients treated with TA-ERT relative to declines observed in untreated patients. Press release from Spruce.
April 2025
Spruce Biosciences, Inc. announced its acquisition of Allievex’s AX 250 tralesinidase alfa enzyme replacement therapy for the treatment of Sanfilippo Syndrome Type B (MPS IIIB). The product will now be called TA-ERT. Spruce plans to submit a Biologics License Application (BLA) for TA-ERT to the FDA in the first half of 2026. Read Spruce’s statement.
November 2024
Allievex released the following statement …
We are pleased to announce that the acquisition of the AX 250 (tralesinidase alfa) program for the treatment of MPS IIIB has been completed. The program will be transitioned to a new team that brings not only deep expertise but also the funding and resources necessary to advance this important therapy with urgency and care. While a formal public announcement will be made in mid-December, we want to assure you that work is already underway to reinitiate the program.
To ensure a smooth transition and preservation of the many years of know-how associated with the program, the Allievex team will be working closely with the new team in the coming months. Our initial focus will be on restarting manufacturing, as there is currently no drug product available. Completing this critical step will allow us to move forward and restart the clinical program.
We understand there may be many questions:
- When will the next confirmatory clinical trial begin?
- Will patients who were previously treated with AX 250 have access to the drug soon?
- Will there be an Expanded Access Program?
- When will you submit for approval of AX 250?
While we do not have answers to these questions now, we ask for your patience as both teams work closely to formulate a plan to get AX 250 to patients as quickly and safely as possible. Please feel free to share this information with your families and network.
July 2024
Allievex terminated its business operations in October 2023, including all clinical studies treating children with Sanfilippo syndrome type B with our enzyme replacement therapy, tralesinidase alfa (AX 250). Simultaneously, Allievex sought a buyer for its program, while also working to initiate investigator-sponsored treatments of some children who were previously receiving AX 250. In July 2024, Allievex announced that it was unable to find a path forward for a potential acquirer and has filed for formal liquidation of assets to pay creditors. Read the statement from Allievex
Comments from Cure Sanfilippo Foundation: It is with very heavy hearts that we share this update from Allievex. Cure Sanfilippo Foundation has worked alongside the Allievex team and patient families to share the real world impact of AX 250 with FDA regulators over the years. This spring we were so encouraged by FDA’s agreement to accept spinal fluid heparan sulfate levels as a surrogate biomarker in a future accelerated approval application. Sadly, in the business lifecycle of this drug development program, time was not on our side. Our community will continue to press forward to support the development of treatments for those who are losing access to this treatment and all individuals affected by Sanfilippo type B.
November 2022
Researchers publish 1-year study findings from the trial. Results demonstrate normalization of cerebrospinal fluid (CSF) levels of heparan sulfate, significant reduction of blood plasma levels of heparan sulfate and liver size. Brain MRIs showed initial loss of brain volume at 6 months but then stabilization in rate of brain atrophy compared to untreated patients, with 9 patients regaining some brain volume by 1 year of treatment. “Tralesinidase Alfa ERT Found to Benefit Sanfilippo Type B Children” is published in The Journal of Clinical Investigation.
March 2020
The clinical trial is now listed as “active, but not recruiting” on ClinicalTrials.gov, meaning the trial is ongoing but no longer accepting participants.
October 2019
Allievex obtains an exclusive worldwide license for tralesinidase alfa from BioMarin. It has assumed all financial obligations associated with the therapy’s development and commercialization and will manage all studies in the clinical program, which it declares will continue uninterrupted.
February 2018
Biomarin presents interim data at the WORLDSymposium 2018. Read the press release.
May 2016
A clinical trial delivering the experimental enzyme replacement therapy (ERT) tralesinidase alfa (BMN 250), sponsored by Biomarin, is now listed as “recruiting” on ClinicalTrials.gov. This is a global study including sites in the United States (California), Columbia, Germany, Spain, Taiwan, Turkey, and the United Kingdom.