Aeglea BioTherapeutics reports repeat dose data from Phase 1/2 trial of AEB1102
Aeglea BioTherapeutics reported new repeat dose data from its Phase 1/2 open-label trial of pegzilarginase in patients with Arginase 1 Deficiency. Aeglea presented repeat dose data from the Phase 1/2 clinical trial of pegzilarginase for two adult patients and single ascending dose data for one pediatric patient with Arginase 1 Deficiency at the 2018 Society for Inherited Metabolic Disorders Annual Meeting on March 12, 2018. Sustained lowering of plasma arginine was achieved with repeated weekly IV dose of 0.04 mg/kg of pegzilarginase. Arginine-derived metabolites elevated at baseline were rapidly decreased and reductions maintained with repeat doses of pegzilarginase. Pegzilarginase was well tolerated with the exception of a single infusion-associated reaction in one pediatric patient who had anti-drug antibodies and blunting of the expected reduction in plasma arginine after the second dose. The patient transitioned to the repeat dose part of the trial and received three further infusions. Although dosing was well tolerated with premedication and slower infusion rates, the patient withdrew consent due to the burden of balancing school and the clinical trial. No marked or sustained increase in ADA titers were seen in the two adult Arginase 1 Deficiency patients or in the 48 cancer patients tested after dosing with pegzilarginase. Baseline ADA at low titer was detected in one of two adult Arginase 1 Deficiency patients and four of 48 cancer patients. There was no apparent effect of the presence of the ADA on arginine reduction or safety profile. The effects of repeat dosing of pegzilarginase provides an opportunity to evaluate the clinical benefits of sustained reduction of plasma arginine beyond what can be achieved with standard of care therapy. The Company expects to report pediatric and adult repeat dose data in patients with Arginase 1 Deficiency in the third quarter of 2018. The first uveal and cutaneous melanoma patients were dosed with pegzilarginase in Aeglea's open-label Phase 1 cohort expansions, with the intent to confirm the safety profile and Phase 2 dose and identify further signals of clinical activity. The Company expects to report Phase 1 cohort expansion topline data, including safety and clinical activity, in the fourth quarter of 2018.