The FDA requested more data on effectiveness, particularly evidence that shows plasma arginine and metabolic reduction can predict clinical benefit in patients living with ARG1-D.
Sarah Silbiger/Getty Images
The U.S. Food and Drug Administration issued a Refusal to File (RTF) letter to Aeglea Biotherapeutics regarding the latter’s proposed drug for Arginase 1 Deficiency.
The RTF, revealed by the company Thursday, is in response to Aeglea’s Biologics License Application for pegzilarginase, which it filed in mid-April 2022. It is the firm’s first-ever BLA, which it was hoping would receive a more positive regulatory reception.
Pegzilarginase is a recombinant human arginase 1 enzyme that works by degrading arginine amino acids and normalizing the elevated levels. People living with ARG1-D experience mobility limitations due to severe spasticity, development delays, intellectual disability, seizures and early mortality. Aeglea’s BLA was based on positive results from its Phase III PEACE trial, presented at the Society of Inherited Metabolic Disorders annual meeting in April.
To make the long story short, the company and even its shareholders were hopeful of an approval.
However, the outcome was the opposite. In the FDA’s RTF letter, the regulator requested more data to support claims of effectiveness, particularly evidence that shows plasma arginine and metabolic reduction can predict clinical benefit in patients living with ARG1-D. The FDA also sought additional data demonstrating a “treatment effect on clinically meaningful outcomes.” In addition, the regulator asked for more details on Chemistry Manufacturing and Controls (CMC).
No safety concerns were raised in the RTF. Aeglea said it will schedule a Type A meeting to clarify the concerns and respond accordingly to help move the proposed drug forward.
“We believe the requests identified in the RTF letter related to CMC can be readily addressed and we intend to work collaboratively with the FDA to identify a viable path forward to demonstrate that lowering plasma arginine confers clinical benefit,” Anthony G. Quinn, president and chief executive officer of Aeglea said in a statement.
“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. We believe pegzilarginase has the potential to help fulfill this unmet medical need. We remain committed to supporting the ARG1-D community and will continue our work to bring this potentially life-changing medicine to patients,” Quinn added.
ARG1-D currently has no FDA-approved treatment.
Perzilarginase already has multiple regulatory designations from the FDA, including Rare Pediatric Disease, Breakthrough Therapy, Fast Track and Orphan Drug Designations. It also has an Orphan Drug Designation from the European Medicines Agency. Aeglea plans to submit a Marketing Authority Application to the EMA this year.
