Ultragenyx’s Angelman Drug Misses Goals in Late-Stage Study

Rare Daily Staff

Ultragenyx Pharmaceutical said its experimental Angelman syndrome therapy, apazunersen, failed to show a benefit over a comparison group in a phase 3 study in children with the rare neurodevelopmental condition.

The drug missed the study’s primary endpoint: improvement from baseline on a standardized measure of cognitive development. It also missed a key secondary endpoint assessing whether participants improved across several areas important to families, including cognition, receptive language, behavior, gross motor skills, and sleep.

The company said it will review the results and decide whether to continue developing the drug.

Angelman syndrome is a rare genetic neurodevelopmental condition that can cause significant challenges with learning, speech, movement, balance, sleep, and seizures. There are no FDA-approved treatments that address its underlying cause.

Apazunersen, also known as GTX-102, is an experimental antisense oligonucleotide therapy administered by intrathecal injection. It is designed to inhibit -AS, a genetic transcript that silences the paternally inherited copy of the gene in neurons. The goal is to reactivate expression of the paternal gene copy and increase production of the deficient UBE3A protein.

The FDA has granted apazunersen Breakthrough Therapy, Orphan Drug, Rare Pediatric Disease, and Fast Track designations. The European Medicines Agency has granted the therapy Orphan Drug and PRIME designations.

The company’s Aspire study tested apazunersen in children ages 4 to 17 with a common genetic form of Angelman syndrome. The study enrolled about 129 participants and compared the therapy, delivered by spinal injection, with a sham procedure over 48 weeks.

Ultragenyx said children assigned to apazunersen did not show differences from those in the comparison group that supported the treatment’s effectiveness on either the cognitive assessment or the broader multidomain measure. The treatment’s safety findings were generally consistent with those observed in earlier studies.

Ultragenyx said it will determine the future of the apazunersen program after evaluating the phase 3 data. The company also plans significant cost reductions while continuing to invest in its commercial rare-disease products and other pipeline programs.