ABO-102 gene therapy increases brain volume in Sanfilippo type A: MRI data

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A single high dose of ABO-102, the experimental gene therapy from Abeona Therapeutics, prevented brain shrinkage associated with the disease in three young children with Sanfilippo syndrome type A up to two years old, data shows provisional updates of the Transpher A Phase 1/2 clinical trial.

“Brain volume loss is characteristic in children with MPS IIIA [Sanfilippo type A] and is associated with long-term cognitive and physical disability, ”said Vishwas Seshadri, PhD, head of research and clinical development at Abeona, in a press release.

“The new MRI data show the potential of ABO-102 to increase the volumes of cerebral gray matter, corpus callosum and tonsil and is consistent with previously reported results of preservation of neurocognitive development in these three young patients. in the Transpher A study, “he added.

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“Gray matter is important for cognitive development, the corpus callosum for motor function, and the amygdala for fear learning as well as social / emotional development,” Seshadri said.

These findings were shared in an oral presentation at the 16th International Symposium on MPS and Related Diseases, which was held virtually July 23-25.

Additionally, based on a recent meeting with the U.S. Food and Drug Administration (FDA), if the Transpher A study continues to produce strong, positive results, Abeona will not need to conduct any further research. further trials to support the filing of a regulatory application for the ABO-Approval of 102 for the treatment of Sanfilippo type A.

The meeting also helped define the most appropriate primary objective of the study to support a potential deposit: a neurocognitive assessment based on the Bayley scales for infant and toddler development and the battery assessment of Kauffman for kids. These two measures were already part of the objectives of Transpher A.

“We are grateful to the FDA for its guidance and collaborative exchange regarding the pivotal trial to support the delivery of ABO-102 to patients with MPS IIIA who currently have no approved treatment,” said Michael Amoroso , CEO of Abeona, in a separate press release announcing the results. Of the reunion.

“From 2016 to date, we have treated 21 patients in the Transpher A trial,” Amoroso said, adding that the company was “excited about the safety and the magnitude of the benefits seen” with ABO-102 at the youngest children who received the higher dose.

“We remain hopeful that if the children who most recently received [the highest dose group] show a similar processing effect, we might have an evaluable data set in 2022, ”Amoroso said.

Abeona plans to work closely with the FDA to assemble the most robust critical data package possible for ABO-102’s regulatory filing.

Sanfilippo syndrome type A, also known as mucoplysaccharydosis IIIA (MPS IIIA), is caused by a deficiency in the heparan N-sulfatase enzyme due to mutations in the SGSH uncomfortable.

Heparin N-sulfatase deficiency results in the toxic build-up of a complex sugar molecule called heparan sulfate, resulting in progressive and severe neurodegeneration.

Administered as a single infusion into the bloodstream, ABO-102 uses a modified and harmless adeno-associated virus to deliver a working copy of the SGSH gene to cells. As such, the therapy has the potential to prevent the build-up of heparan sulfate and stop or reduce neurodegeneration in type A Sanfilippo patients.

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ABO-102 has received the Regenerative Medicine Advanced Therapy, Orphan Drug, Rare Pediatric Disease, and Expedited Therapy designations in the United States, as well as Orphan Drug and Priority Drug designations in Europe. These designations are intended to accelerate the clinical development and regulatory review of ABO-102.

The international phase 1/2 study Transpher A (NCT02716246) evaluates the safety and efficacy of three doses of ABO-102 – 5 × 1012, 1 × 1013, and 3 × 1013 vector genomes (vg) / kg – in up to 22 infants and children with Sanfilippo type A.

Eligible patients are those under 2 years of age or those over 2 years of age with a cognitive development quotient of 60% or greater.

The primary objectives of Transpher A are to assess the safety of therapy and the neurological development of children up to two years after dosing.

Secondary goals include changes in heparan N-sulfatase activity in the cerebrospinal fluid (CSF, the fluid that surrounds the brain and spinal cord) and blood; level of heparan sulfate in CSF, blood and urine; brain volume, behavior, quality of life and liver volume.

Previous data from the first 19 patients treated (three in the low and medium dose group each, and 13 in the high dose group) showed that the highest dose ABO-102 led to dose-dependent and significant reductions in several disease biomarkers, such as heparan sulfate and liver volume, for up to two years after treatment.

This high dose also maintained normal cognitive development for up to three years in three young children, aged 3.5 to over 5 years at the time of analysis. At these ages, untreated Sanfilippo type A patients already show cognitive decline.

Newly presented data now shows that these three children also had an increase in brain volume two years after dosing, compared to untreated patients of the same age.

Together, these results highlight the potential of a single dose of ABO-102 to prevent brain shrinkage and cognitive decline in young children with Sanfilippo type A.

To date, treatment has been generally well tolerated at all three doses, with most adverse events being mild to moderate in intensity and easily resolving. No deaths, infusion-related adverse events or clinically significant adverse events were reported.

ABO-101, Abeona’s experimental gene therapy for Sanfilippo type B, also showed promising results in the phase 1/2 Transpher B trial (NCT03315182), which is similar in design to Transpher A.

The trial was in the process of completing its target recruitment of 15 children, according to the company, and two-year data from the first patients treated with the high dose is expected in the first half of 2022.

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