Ultragenyx Acquires ABO-102, Potential Sanfilippo Type A Gene Therapy

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Ultragenyx Pharmaceutical has closed an agreement giving it global licensing, manufacturing, and commercialization rights to UX111 (formerly ABO-102), an experimental gene therapy for Sanfilippo syndrome type A being tested in the pivotal Phase 1/2 Transpher A trial.

Ultragenyx will assume responsibility for UX111’s clinical program, while the therapy’s developer, Abeona Therapeutics, will be eligible to receive royalty payments of up to 10% on net sales and up to $30 million if certain commercial milestones are met.

“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, Ultragenyx’s CEO and president, said in a press release.

Based on a meeting last year between Abeona and the U.S. Food and Drug Administration (FDA), the trial’s results, should they be positive, will be enough to support a regulatory filing seeking the therapy’s approval in the U.S. for Sanfilippo type A, also known as mucopolysaccharidosis IIIA (MPS IIIA).

Notably, the latest interim findings, recently presented at the American Society of Gene & Cell Therapy annual meeting, held May 16–19 in Washington, D.C., showed that UX111’s therapeutic dose was generally safe and defied Sanfilippo type A’s natural course in children with early-stage disease.

The oral presentation was titled “Updated Interim Results of Transpher A, a Multicenter, Single-Dose, Pivotal Clinical Trial of ABO-102 Gene Therapy for Sanfilippo Syndrome Type A (Mucopolysaccharidosis IIIA).”

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“Based on promising data from Abeona’s clinical program, regulatory feedback to date, and our experience developing treatments for other MPS diseases, we believe ABO-102 has the potential to be a transformative therapy for patients with MPS IIIA,” Kakkis said.

Ultragenyx also developed, and currently markets, 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 gene therapy clinical 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, Abeona’s CEO, said that “data from the ongoing Transpher A trial demonstrate ABO-102 holds significant potential to improve outcomes for patients with MPS IIIA who experience relentlessly progressing neurodevelopmental and physical decline that is life-threatening at a very young age.”

Seshadri added, “We believe that Ultragenyx, with deep expertise in rare, genetic, metabolic lysosomal storage disorders and a demonstrated commitment towards 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 result in toxic GAG accumulation within 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 deficient heparan N-sulfatase enzyme — which breaks down a GAG called heparan sulfate — due to mutations in the SGSH gene.

Administered through a single infusion into the bloodstream, UX111 uses a modified and harmless adeno-associated virus (AAV) to deliver a working copy of the SGSH gene to cells. As such, it has the potential to prevent heparan sulfate buildup and halt or lessen neurodegeneration in Sanfilippo type A patients.

The therapy has received orphan drug, regenerative medicine advanced therapy, rare pediatric disease, and fast track designations in the U.S. and orphan drug and priority medicines designations in Europe for Sanfilippo type A. These designations are meant to accelerate its clinical development and regulatory review.

The international, Phase 1/2 Transpher A study (NCT02716246) is evaluating the two-year safety and effectiveness of three doses of UX111  — 0.5×1013, 1×1013, and 3×1013 vector genomes (vg)/kg — in up to 22 infants and children with early-stage Sanfilippo type A.

The trial may still be recruiting at sites in the U.S., Australia, and Spain; more information can be found here.

Eligible participants include those aged 6 months to 2 years, or those older than 2 with a cognitive developmental quotient (DQ) of 60 or above, indicating mild impairment (normal scores, 85 or higher). DQ is a measure of developmental ability compared to what’s normal for a specific age, similar to intelligence quotient for cognitive ability.

Transpher A’s main goals are to assess the therapy’s safety and the children’s neurodevelopment, while secondary goals include changes in behavior, brain and liver volume, quality of life, heparan N-sulfatase activity, and the levels of biomarkers, such as heparan sulfate, in bodily fluids.

After completing the two-year trial, participants may enter a long-term study (NCT04360265), in which they will be followed for an additional three years.

Consistent with previously reported interim data, newly presented findings, with follow-up data up to nearly 5.5 years, showed that the therapy was generally well tolerated across all doses and that the highest dose, deemed 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 tracked along the normal development range of a nonaffected child.

They also exhibited behavioral improvements, overall stabilization of brain and liver volumes, and sustained and significant reductions in disease-specific biomarkers, compared with untreated patients of the same age and those given the lowest, subtherapeutic, doses.

These findings are in sharp contrast with the disease’s natural course.

“The promising results to date suggest a single [into-the-vein] dose of ABO-102 AAV-based gene therapy has the potential to help children with MPS IIIA sustain neurocognitive development when they are treated during early stages of their disease,” said Kevin Flanigan, MD, Transpher A’s principal investigator and the director of the Center for Gene Therapy at Nationwide Children’s Hospital in Columbus, Ohio.

Earlier this year, Abeona discontinued a trial (NCT04088734) that was testing ABO-102 in children, ages 2 to 17, with relatively advanced Sanfilippo A — DQ lower than 60 — due to lack of neurocognitive improvements.