Aeglea Presents Additional Data from Phase 3 Study of Pegzilarginase in ARG1-D, Shares Rise

Shares of Aeglea BioTherapeutics rose 30 percent after the company shared positive additional data from the PEACE phase 3 study of its lead experimental compound pegzilarginase, including new data on patient-level outcomes, additional secondary endpoints, and previously announced topline results.

Photo: Anthony Quinn, president and CEO of Aeglea

The data was presented in poster presentation at the Society for Inherited Metabolic Disorders Annual Meeting being held in Orlando, Florida.

The additional data buoy the prospects for pegzilarginase after Aeglea reported in December 2021 that it met the primary endpoint in the PEACE study in patients with the rare metabolic disease arginase 1 deficiency, but failed to show statistically significant improvements in the secondary endpoint of improvement 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, even though there was a positive trend in the treatment group.

Pegzilarginase is a novel, recombinant human arginase 1 enzyme that has been shown in clinical trials to normalize the elevated levels of the amino acid arginine in patients with arginase 1 deficiency (ARG1-D), a rare, progressive disease characterized by high levels of arginine. People living with ARG1-D experience severe spasticity-related mobility limitations, seizures, developmental delay, intellectual disability, and early mortality.

“Our clinical development program for pegzilarginase has provided the first quantitative insights into the disease burden of ARG1-D and sheds new light on both the severity of the disease and the devastating effect of uncontrolled arginine levels in these patients,” said Anthony Quinn, president and CEO of Aeglea. “The data from PEACE show the ability of pegzilarginase to markedly improve arginine control and its impact on a broad range of disease-related abnormalities. We are pleased with these results and believe pegzilarginase has the potential to change the lives of the patients and families living with ARG1-D.”

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 versus placebo from baseline through a prespecified 24-week treatment period.

The company previously announced that the study reached the primary endpoint with a highly statistically significant 76.7 percent reduction in mean plasma arginine in pegzilarginase treated patients compared to placebo. Normal plasma arginine levels were achieved in 90.5 percent of pegzilarginase treated patients compared to no patients in the placebo arm. Accompanying improvements in the key secondary mobility assessment in pegzilarginase treated patients compared to patients in the placebo arm, the least squares mean GMFM-E score, was not statistically significant but established a positive trend.

Pegzilarginase was well-tolerated and safety data were consistent with results from previous clinical trials. Adverse events were generally mild to moderate in severity. There were no study discontinuations due to adverse events.

In a post hoc analysis correcting for a missed assessment that was improperly scored as 0 rather than “not assessed,” the least squares mean GMFM-D score of patients treated with pegzilarginase improved from baseline by 2.25 units compared to placebo.

Pegzilarginase treated patients also showed statistically significant biochemical improvements in measures of ornithine and guanidino compounds compared to placebo, consistent with pegzilarginase mechanism of action.

“It is great to see these additional results and the consistency of the effects as we conduct further analysis of the data from the PEACE phase 3 study. The lowering of guanidino compounds, downstream metabolites of arginine, supports the mechanism of action of pegzilarginase in lowering arginine levels, the key driver of disease,” said Eric Bradford, chief development officer at Aeglea. “In rare diseases, and in particular trials conducted in small patient populations, much of the story unfolds in looking at the individual patient responses. We are excited about the results that we see from PEACE with nearly half of the evaluable pegzilarginase treated patients demonstrating clinically meaningful improvement in two or more mobility assessments. This is a remarkable result given that ARG1-D is a progressive disease with a devastating impact on mobility.”

Pegzilarginase has received multiple regulatory designations, including Rare Pediatric Disease, Breakthrough Therapy, Fast Track, and Orphan Drug designations from the U.S. Food and Drug Administration as well as Orphan Drug designation from the European Medicines Agency.

Author: Rare Daily Staff