FDA Issues Refusal to File Letter to Aeglea BioTherapeutics for Arginase 1 Deficiency

The U.S. Food and Drug Administration issued Aeglea BioTherapeutics a Refusal to File letter saying it would not review the company’s Biologics License Application for pegzilarginase for the treatment of Arginase 1 Deficiency.

Photo: Anthony Quinn, president and CEO of Aeglea

Aegela shares fell 50 percent on the news to 76 cents on the Nasdaq GM.

The agency requested additional data to support effectiveness, such as evidence showing that plasma arginine and metabolite reduction predicts clinical benefit in patients with ARG1-D or clinical data demonstrating a treatment effect on clinically meaningful outcomes. The FDA also requested additional information relating to Chemistry Manufacturing and Controls. There were no issues related to safety raised in the letter.

Arginase 1 Deficiency is a rare, progressive and debilitating 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. There are currently no FDA-approved treatments for this indication. Pegzilarginase is a novel, recombinant human arginase 1 enzyme that in clinical trials has been shown to normalize the elevated levels of the amino acid arginine in patients with ARG1-D.

Pegzilarginase is a novel recombinant human enzyme engineered to degrade the amino acid arginine and has been shown to rapidly and sustainably lower levels of the amino acid arginine in plasma. Aeglea is developing pegzilarginase for the treatment of people with Arginase 1 Deficiency (ARG1-D), a rare debilitating and progressive disease characterized by the accumulation of arginine. ARG1-D presents in early childhood and patients experience spasticity, seizures, developmental delay, intellectual disability and early mortality.

Aeglea’s application submission included positive results from its double-blind, placebo-controlled PEACE phase 3 study and its ongoing long-term extension study as well as a phase 1/2 clinical trial and its open-label extension study. The totality of data demonstrates that pegzilarginase is able to rapidly and sustainably lower arginine levels and is accompanied by improvements in mobility. In the PEACE study, most treatment-emergent adverse events were mild or moderate in severity and there were no discontinuations due to treatment-emergent adverse events. The FDA has granted pegzilarginase multiple regulatory designations, including Rare Pediatric Disease, Breakthrough Therapy, Fast Track and Orphan Drug designations.

Immedica Pharma AB, Aeglea’s commercialization partner for pegzilarginase in Europe and the Middle East, has recently met with the European Medicines Agency regarding the Marketing Authorization Application for pegzilarginase, which is planned to be submitted in 2022.

Aeglea said it intends to request a meeting with the FDA to clarify and respond to the items identified in the Refusal to File letter.

Anthony Quinn, president and CEO of Aeglea, said he believes the CMC issue raised by the FDA can be readily addressed and that the company will work collaboratively with the agency to identify a viable path forward.

“While we are disappointed in the outcome of the FDA’s initial review of our BLA, we continue to believe in the potential of pegzilarginase and thank the FDA for their constructive comments and ongoing collaboration,” he said. “Without access to any approved therapies for ARG1-D, patients and their families face worsening outcomes and increasing challenges—every day matters to them. We believe pegzilarginase has the potential to help fulfill this unmet medical need.”

Author: Rare Daily Staff