Ultragenyx Pharmaceutical Inc. announced the successful completion of an end-of-Phase 2 (EoP2) meeting with the U.S. Food and Drug Administration (FDA), supporting its Phase 3 study plans for GTX-102, an antisense oligonucleotide for Angelman syndrome. The EoP2 meeting focused on discussion of the Company?s interim Phase 1/2 data and resulted in alignment with the FDA on the Phase 3 study design and endpoints. The pivotal Phase 3, will be a global, randomized, double-blind, sham-controlled trial and will include a 48-week primary efficacy analysis period enrolling approximately 120 patients with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion.

The primary endpoint will be improvement in cognition assessed by Bayley-4 cognitive raw score. Control patients completing the study will be eligible to roll over onto treatment after the double-blind period is over. Previously disclosed results from the Phase 1/2 study showed that UBE3A gene deletion patients treated with GTX-102 experienced rapid, progressive and clinically significant improvement in cognition, as assessed by Bayley-4, that was far greater than the minimal change observed in Natural History data1 in deletion patients.

UBE3A gene deletion patients are at the severe end of the clinical spectrum, with lower Bayley scores at baseline, and demonstrate a much slower rate of skill attainment compared to, for example, UBE3A missense mutation patients, who demonstrate higher Bayley cognition improvement in Natural History data.2 In the Phase 1/2 study, GTX-102 treated patients also demonstrated meaningful improvements in other domains of communication, motor function, sleep problems, and behavior. The Phase 3 study will include the key secondary endpoint of the Multi-domain Responder Index (MDRI) across all five domains of cognition, receptive communication, behavior, gross motor function, and sleep. Individual secondary endpoints were also discussed and aligned on with the FDA for the domains of communication, behavior, motor function and sleep.

Additional feedback on the conduct and analysis of these endpoints may be received from the FDA?s Division of Clinical Outcomes Assessment. The company has also participated in a PRIME meeting with the European Medicines Agency, receiving acceptance of the overall Phase 3 study design, dosing and evaluations. The company expects to meet with Japan?s Pharmaceuticals and Medical Devices Agency in the coming weeks to inform and discuss the Phase 3 study design.

The company has also participated in a PRIME meeting with the European Medicines Agency, receiving acceptance of the overall Phase 3 study design, dosing and evaluations. The company expects to meet with Japan?s Pharmaceuticals and Medical Devices Agency in the coming weeks to inform and discuss the Phase 3 study design.