Aeglea BioTherapeutics has submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for its lead drug candidate pegzilarginase, requesting Priority Review for the treatment of Arginase 1 Deficiency (ARG1-D). If approved, pegzilarginase would become the first FDA-authorized therapy addressing this rare genetic disorder.
The company's stock rose over 5% following the announcement, trading at $2.56 on Nasdaq, reflecting investor optimism about the potential commercial opportunity.
Strong Phase III Results Support Regulatory Filing
The BLA submission is supported by compelling data from the successfully completed Phase III PEACE trial, which evaluated pegzilarginase in patients aged two years and older with ARG1-D. The study met its primary endpoint with a statistically significant 80% reduction in mean plasma arginine levels in treated patients compared to placebo.
Notably, 90.5% of subjects receiving pegzilarginase achieved normalization of plasma arginine to levels between 40-115μM, while no patients in the placebo group reached this benchmark. These results demonstrate the drug's ability to address the fundamental biochemical abnormality in ARG1-D.
Additional data released from the PEACE study showed that pegzilarginase-treated patients exhibited statistically significant biochemical improvements in ornithine and guanidino compounds compared to placebo, consistent with the drug's mechanism of action as a recombinant human arginase 1 enzyme.
Understanding Arginase 1 Deficiency
ARG1-D is a progressive rare disease characterized by abnormally high levels of the amino acid arginine. The condition manifests with severe clinical symptoms including spasticity-related mobility limitations, seizures, developmental delay, intellectual disability, and early mortality.
Currently, there are no FDA-approved treatments specifically targeting the underlying cause of ARG1-D, representing a significant unmet medical need for affected patients and their families.
Global Regulatory Strategy
While pursuing FDA approval in the United States, Aeglea is simultaneously advancing international regulatory efforts. The company's commercialization partner, Immedica Pharma AB, plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency later this year for certain countries in Europe and the Middle East.
Commercial Potential
If approved, pegzilarginase could achieve peak annual sales between $300 million and $400 million, according to analyst projections. This revenue potential highlights the significant commercial opportunity despite the relatively small patient population typical of rare diseases.
The drug's novel mechanism as a recombinant human arginase 1 enzyme has been shown to effectively normalize elevated arginine levels in clinical trials, potentially addressing the fundamental cause of ARG1-D rather than just managing symptoms.
Next Steps
The FDA will now review the BLA submission and determine whether to grant Priority Review status, which could expedite the regulatory timeline. Aeglea's request for Priority Review reflects the serious nature of ARG1-D and the lack of approved treatment options.
Industry observers will be watching closely for the FDA's acceptance of the application and subsequent review timeline, which will provide further insight into the potential market entry date for this first-in-class therapy.
