Aeglea BioTherapeutics, Inc. announced that the pivotal Phase 3 study, PEACE (Pegzilarginase Effect on Arginase 1 Deficiency Clinical Endpoints), met the primary endpoint with a statistically significant reduction in plasma arginine from baseline after 24 weeks of treatment with pegzilarginase (p <0.0001). Importantly, pronounced and sustained plasma arginine reduction was accompanied by a positive trend in Gross Motor Function Measure Part E (GMFM-E), a key clinical assessment of a patient's mobility, including the ability to walk, run and jump. PEACE is the first placebo-controlled clinical trial ever conducted in Arginase 1 Deficiency (ARG1-D) and pegzilarginase is the first potential therapy to normalize the markedly elevated plasma arginine levels in these patients. Based on the results of this trial, Aeglea plans to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) in the first half of 2022. Additionally, Aeglea will work with Immedica Pharma AB, its commercial partner in Europe and certain countries in the Middle East, to submit marketing authorization applications in those territories. ARG1-D is a rare, progressive and debilitating disease characterized by high levels of the amino acid arginine. The disease manifestations include spasticity, developmental delay, intellectual disability and seizures. The functional disability and impact on daily life creates a significant burden for patients and caregivers. There are currently no FDA-approved treatments that address elevated arginine, the key driver of ARG1-D. Current standard of care includes severe dietary protein restriction and essential amino acid supplementation, which does not effectively or sustainably reduce high arginine levels. PEACE is a global, randomized, double-blind, placebo-controlled trial that enrolled 32 patients with ARG1-D aged two years and older. The study was designed to assess the effects of treatment with pegzilarginase (n=21) versus placebo (n=11) from baseline through a prespecified 24-week treatment period. The primary endpoint assessed plasma arginine reduction from baseline levels. The key secondary endpoint evaluated mobility using GMFM-E, which consists of 24 tasks involving walking forward/backward, running, jumping and ascending/descending stairs, and the 2-Minute Walk Test (2MWT), a measure of the distance a patient walks in two minutes. Other secondary endpoints included additional outcome assessments, safety and pharmacokinetics. Topline results are summarized as follows: PEACE demonstrated a highly statistically significant 80% reduction in mean plasma arginine in pegzilarginase treated patients (p<0.0001), the primary endpoint of the trial. Importantly, normal plasma arginine levels (40-115µM) were achieved in 90.5% of pegzilarginase treated patients compared to none of the patients in the placebo arm. The least squares mean GMFM-E score improved by 4.2 units for pegzilarginase treated patients and worsened by 0.4 units in the placebo arm (p=0.1087; 95% CI [-1.1, 10.2]), establishing a positive trend in this mobility assessment. The least squares mean 2MWT distance increased 7.4 meters in pegzilarginase treated patients and 1.9 meters in the placebo arm (p=0.5961; 95% CI [-15.6, 26.7]). Pegzilarginase was well-tolerated and safety data were consistent with results from previous clinical trials. There were no study discontinuations due to adverse events. All 31 patients who completed the 24-week double-blind study period continued into the Long-Term Extension (LTE) portion of the PEACE trial. In addition, 13 of the 14 patients in the ongoing Phase 1/2 Open Label Extension (OLE) trial have continued pegzilarginase therapy ranging from 2 to 4 years. The previously presented 56-week data from the Phase 1/2 OLE trial supports the long-term clinical benefit of pegzilarginase treatment. The company believes that the entirety of data from the pegzilarginase program supports the long-term clinical benefit of pegzilarginase in ARG1-D. Additional data from the pegzilarginase program are expected to be presented at upcoming medical meetings and submitted to peer-reviewed medical journals.