Benzinga | Jan 5, 2022 08:09AM EST

Ultragenyx, GeneTx Provide Preliminary Update On Phase 1/2 Clinical Study Of GTX-102 In Canada And UK Patients With Angelman Syndrome

GeneTx Biotherapeutics LLC and Ultragenyx Pharmaceutical Inc. (NASDAQ:RARE), companies partnered in the development of GTX-102, an investigational treatment for Angelman syndrome, today announced that the first four patients in the Phase 1/2 study have received multiple doses of GTX-102 and regular assessments for safety. To date three have also received a preliminary assessment of clinical response. There have been no treatment-related serious adverse events of any type nor adverse events related to lower extremity weakness observed in these patients, and initial assessments have shown early signs of clinical activity.



The data safety monitoring board (DSMB) met to discuss the assessments for the first two patients in Cohort 4 (ages 4 to <8 years) and recommended that dose escalation may proceed as planned and the study may enroll the remaining four patients in this cohort. Since then, both patients in Cohort 4 met the criteria to increase their doses and have each escalated to the 5 mg dose, and Cohort 4 has been expanded and an additional patient has received their first dose. The DSMB for Cohort 5 (ages 8 to <18 years) is expected to meet soon and confirm whether enrollment for the remaining four patients in that group may commence. Data on full Cohorts 4 and 5 in the Canada/U.K. arm of the study is anticipated in mid 2022 after completing Day 128 of the protocol.

"We are encouraged by the safety, the initial impressions from the investigators and the improvements observed in the clinical global impression scale from early assessments. The changes in multiple functional domains are encouraging and similar to the reported early changes in the original patients from the initial part of the study at these doses," said Scott Stromatt, M.D., Chief Medical Officer of GeneTx. "It is still early in the study and we look forward to the full assessments at the completion of the Day 128 study visit."

The open-label, multiple-dose, dose-escalating Phase 1/2 study is evaluating the safety, tolerability and efficacy of GTX-102 in pediatric patients with Angelman syndrome who have a genetically confirmed diagnosis of full maternal UBE3A gene deletion. The study will evaluate the overall Clinical Global Impression -- Improvement (CGI-I) scale of change at Day 58 and again at Day 128, at which time a panel of other efficacy assessments for the domains impacted in Angelman, including communication, sleep, behavior, gross motor skills, fine motor skills, and seizures will also be measured.

GTX-102 Phase 1/2 Study Design in Canada and the U.K.

Under the protocol approved in Canada and the U.K., 12 patients will be enrolled into two cohorts split by age: patients ages 4 to <8 years will be enrolled into Cohort 4, and patients ages 8 to <18 years will be enrolled into Cohort 5. The starting doses in Cohort 4 and Cohort 5 are 3.3 and 5 mg, respectively. Patients will receive two doses and will be assessed for safety and efficacy, as measured by the CGI-I scale of change at Day 58, before moving to step-increases in dosing. Individual dose titration may continue if safety is sustained, and the clinical response is not scored as "much improved" or better by the CGI-I scale in at least two or more domains. If indicated, patients will increase one step for two more doses with dose increases based on clinical response and safety monitoring. Patients will then transition to a maintenance dose 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 up to a maximum dose of 14 mg based on the same criteria of sustained safety and clinical response.