Ultragenyx Pharmaceutical has revealed that its Phase III Aspire study for apazunersen (GTX-102) in Angelman syndrome did not achieve its primary endpoint of change from Baseline in Bayley-4 cognitive raw score. 

The trial also failed to achieve the key secondary endpoint of net response in Multidomain Responder Index (MDRI). 

“Based on everything we observed in the robust Phase I/II clinical development programme and long-term extension study, we are disappointed by the Aspire result,” said Dr Emil Kakkis, Chief Executive Officer and President of Ultragenyx. “We will maintain focus on our growing commercial business, which continues to create meaningful value, including new sources of revenue from the recent approval of Genglycos for glycogen storage disease type Ia, the potential approval of UX111 for Sanfillipo syndrome, and the expansion of existing products to new territories.” 

In Aspire, the randomised groups were comparable at baseline and consistent with the patients studied in Phase II. There were no differences between the treated and control groups that could support efficacy in the Bayley Cognition raw scores nor in the MDRI when looking at net response or mean changes of the individual five endpoints included in the MDRI. 

Apazunersen (GTX-102) is an investigational antisense oligonucleotide (ASO) therapy designed to target and inhibit expression of the UBE3A-AS to prevent silencing of the paternally inherited allele of the UBE3A gene and reactivate expression of the deficient protein.  

It has been granted Breakthrough Therapy Designation, Orphan Drug Designation, Rare Pediatric Disease Designation, and Fast Track Designation from the FDA and Orphan Designation and PRIME designation from the EMA. 

Angelman syndrome is a rare, neurogenetic disorder caused by loss-of-function of the maternally inherited allele of the UBE3A gene. It is a lifelong neurodevelopmental disorder that causes cognitive impairment, motor impairment, balance issues and debilitating seizures.