Benzinga | Jun 10, 2021 08:40AM EDT

GeneTx and Ultragenyx Receive Approval From UK MHRA To Begin Clinical Study Of GTX-102 For The Treatment Of Angelman Syndrome

GeneTx Biotherapeutics LLC and Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE), companies partnered in the development of intrathecally administered GTX-102, an investigational treatment for Angelman syndrome, today announced that the U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) has approved the Clinical Trial Application (CTA) for the Phase 1/2 study of GTX-102 in pediatric patients with Angelman syndrome in the U.K. The companies previously received clearance to enroll patients in the Phase 1/2 study in Canada. The first patients from these regions are expected to be enrolled in the study early in the second half of 2021, with clinical data from some patients in the study expected before the end of the year.

Additionally, GeneTx and Ultragenyx recently met with the U.S. Food and Drug Administration (FDA) and had a productive discussion regarding the Phase 1/2 study. Based on the outcome of the meeting, GeneTx will submit an amended protocol to FDA that addresses key FDA issues.

"We've made significant progress on the regulatory front over the past few weeks with the Phase 1/2 study cleared to begin enrollment in two countries. Based on our recent discussions, we are encouraged about our proposal to begin redosing patients in the U.S. pending FDA agreement," said Scott Stromatt, M.D., Chief Medical Officer of GeneTx. "GTX-102 has demonstrated clinical activity in the first five patients dosed in the study, and the modified trial design approved by the MHRA and Health Canada intends to explore the benefit of repeat doses at the lower end of the dosing range previously tested in order to help mitigate the risk for serious adverse events caused by localized inflammation."

Phase 1/2 study design in U.K. and Canada

The Phase 1/2, open-label, multiple-dose, dose-escalating study evaluates the safety, tolerability, and plasma and cerebrospinal fluid concentrations of GTX-102 in pediatric patients with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion. Under the amended protocol approved in the U.K. and Canada, approximately 12 patients will be enrolled into two cohorts split by age: patients ages 4 to 7 years will be enrolled into Cohort 4, and patients ages 8 to 17 years will be enrolled into Cohort 5.

The starting doses in Cohorts 4 (<8 years old) and 5 (>8 years old) will be 3.3 and 5 mg, respectively. Patients will receive 3 to 4 monthly doses, titrated individually through smaller steps than the first three cohorts in the original study with dose increases based on response and enhanced safety monitoring. Patients will then move to a maintenance phase during which they will receive GTX-102 every three months and continue to be monitored for response and safety. In this phase, individual dose titration may continue if the clinical response is not much improved in at least 2 domains up to a maximum dose of 14 mg.