Arcturus announces ‘positive’ interim Phase 2 multiple dose data for ARCT-810

Arcturus Therapeutics (ARCT) announces “positive” Phase 2 interim results in people with OTC deficiency treated with ARCT-810, an mRNA therapeutic candidate designed to replace the OTC enzyme and restore urea cycle activity preventing hyperammonemia crises. Multiple dosing data are available from two Phase 2 studies; a completed placebo-controlled study in Europe that randomized six participants to ARCT-810 doses and an open-label multiple ascending dose study with interim data from the initial three completed participants. The ongoing U.S. Phase 2 open-label study uses a modified and improved 15N-ureagenesis assay. The assay measures relative ureagenesis function against a normal range established from healthy controls. In the combined analysis of both Phase 2 studies, significantly decreased glutamine levels were observed following multiple ARCT-810 administrations to patients who remained on their standard of care therapy. “These results provide statistical evidence that glutamine levels decrease over time in both Phase 2 studies, suggesting a robust effect across the patient cohorts,” the company stated. In the Phase 2 randomized European study, glutamine levels in patients who received multiple doses of ARCT-810 significantly decreased during the dosing period. In the Phase 2 open-label U.S. study, all three participants had a sustained and significant decrease in glutamine from baseline reaching normal levels after the first three doses. “We are very pleased with these new ARCT-810 clinical results, where we have achieved strong biological effects in both Phase 2 studies, including significant and consistent reduction and normalization of abnormally elevated glutamine, an important biomarker to monitor urea cycle function,” said Dr. Juergen Froehlich, Chief Medical Officer of Arcturus. “Furthermore, in our ongoing U.S. Phase 2 study, we are excited to report the first significant relative ureagenesis function improvements using a new and optimized 15N-ureagenesis assay. Along with the observation of stable ammonia levels in all patients during treatment, these data add a level of robustness to this new interim dataset. I am also very pleased to see that our LUNAR delivery technology continues to be generally safe and well tolerated. The combined biomarker data is unprecedented for an mRNA rare disease therapeutic and, importantly, provides a potentially accelerated path forward to a multi-biomarker driven pivotal study.”