Ultragenyx Pharmaceutical has entered into an agreement granting it worldwide licensing, manufacturing and commercialization rights to UX111 (formerly ABO-102), an investigational gene therapy for Sanfilippo syndrome type A being tested in the pivotal trial of phase 1/2 Transpher A.
Ultragenyx will assume responsibility for the clinical program of UX111, while therapy developer Abeona Therapeutics will be eligible to receive royalties of up to 10% on net sales and up to $30 million upon certain commercial milestones. are reached.
“The Sanfilippo community has been waiting too long for a first treatment and we believe we can help accelerate this program,” Emil D. Kakkis, MD, PhD, CEO and President of Ultragenyx, said in a press release.
Based on a meeting last year between Abeona and the U.S. Food and Drug Administration (FDA), the results of the trial, if positive, will be sufficient to support a regulatory filing requesting the US therapy approval for Sanfilippo type A, also known as mucopolysaccharidosis IIIA (MPS IIIA).
Notably, the latest interim findings, recently presented at the annual meeting of the American Society of Gene & Cell Therapy, held May 16-19 in Washington, DC, showed that the therapeutic dose of UX111 was generally safe and challenged the natural history of Sanfilippo type A in children with -stage of the disease.
The oral presentation was titled “Updated interim results from Transpher A, a single-dose, multicenter pivotal clinical trial of ABO-102 gene therapy for Sanfilippo syndrome type A (mucopolysaccharidosis IIIA).”
“Based on promising data from Abeona’s clinical program, regulatory feedback to date, and our experience in developing treatments for other MPS diseases, we believe that ABO-102 has the potential to be a transformative therapy for patients with MPS IIIA,” Kakkis said.
Ultragenyx has also developed and is currently marketing Mepsevii (vestronidase alfa-vjbk), an approved therapy for people with MPS type VII, also known as Sly syndrome.
“Our team’s expertise in MPS and clinical gene therapy development makes this program a seamless integration, and it has the potential to be our first gene therapy to market,” Kakkis added.
Vish Seshadri, PhD, CEO of Abeona, said, “Data from the ongoing Transpher A trial demonstrates that ABO-102 has significant potential to improve outcomes for patients with MPS IIIA who are experiencing neurodevelopmental decline and constantly progressing physique that puts their lives at risk at a very young age”. age.”
Seshadri added, “We believe Ultragenyx, with deep expertise in rare, genetic and metabolic lysosomal storage disorders and a demonstrated commitment to MPS diseases, is the ideal partner to eventually bring ABO-102 to patients.
MPS is a group of inherited lysosomal storage disorders caused by deficiencies in enzymes responsible for breaking down complex sugar molecules called glycosaminoglycans (GAGs). Such deficiencies lead to a buildup of toxic GAGs in cells, particularly their recycling centers, or lysosomes, leading to progressive damage.
Sanfilippo syndrome type A, characterized by progressive and severe neurodegeneration, is caused by a deficiency in the enzyme heparan N-sulfatase – which breaks down a GAG called heparan sulfate – due to mutations in the SGSH embarrassed.
Administered by a single infusion into the bloodstream, UX111 uses a harmless modified adeno-associated virus (AAV) to provide a working copy of the SGSH gene to cells. As such, it has the potential to prevent heparan sulfate buildup and arrest or reduce neurodegeneration in Sanfilippo A type patients.
The therapy has received Orphan Drug, Advanced Regenerative Medicine Therapy, Rare Pediatric Disease, and Fast Track designations in the United States and Orphan Drug and Priority Drug designations in Europe for Sanfilippo Type A. These designations aim to accelerate its clinical development and regulatory review.
The international Phase 1/2 Transpher A study (NCT02716246) evaluates the safety and efficacy over two years of three doses of UX111 – 0.5 × 10131×1013and 3×1013 vector genomes (vg)/kg — in up to 22 infants and children with early-stage Sanfilippo type A.
The trial can still recruit at sites in the US, Australia and Spain; More information can be found here.
Eligible participants include those aged 6 months to 2 years, or those older than 2 years with a cognitive development quotient (DQ) of 60 or greater, indicating mild impairment (normal scores, 85 or greater). DQ is a measure of developmental ability relative to what is normal for a specific age, similar to intelligence quotient for cognitive ability.
The primary goals of Transpher A are to assess safety of therapy and neurodevelopment in children, while secondary goals include behavioral changes, brain and liver volume, quality of life, activity of heparan N-sulfatase and levels of biomarkers, such as heparan sulfate, in body fluids.
After completing the two-year trial, participants can enter a long-term study (NCT04360265), in which they will be followed for an additional three years.
Consistent with previously reported interim data, the newly presented results, with follow-up data up to nearly 5.5 years, showed that the therapy was generally well tolerated at all doses and that the highest dose, found to be therapeutic , led to significant improvements in several measures.
Most of the 10 children given the highest dose – followed for a median of 28.2 months (nearly 2.5 years) – showed neurocognitive improvement, and six of them followed the normal developmental range. of an unaffected child.
They also showed behavioral improvements, overall stabilization of brain and liver volumes, and sustained and significant reductions in disease-specific biomarkers, compared to age-matched untreated patients and those who received the lowest doses. , subtherapeutic.
These results contrast sharply with the natural course of the disease.
“The promising results to date suggest only one [into-the-vein] gene therapy dose based on ABO-102 AAV has the potential to help children with MPS IIIA maintain their neurocognitive development when treated during the early stages of their disease,” said Kevin Flanigan, MD, researcher principal of Transpher A and director of the Center for Gene Therapy at Nationwide Children’s Hospital in Columbus, Ohio.
Earlier this year, Abeona halted a trial (NCT04088734) that tested ABO-102 in children aged 2 to 17 with relatively advanced Sanfilippo A – DQ less than 60 – due to lack of neurocognitive improvements.