Immedica Gains Accelerated OK for Arginase 1 Deficiency Therapy
FDA has granted Immedica Pharma an accelerated approval for its BLA for Loargys (pegzilarginase-nbln), the first therapy specifically designed to lower plasma arginine in patients with Arginase 1 Deficiency, a rare and progressive metabolic disorder. The action allows Loargys to be used to treat hyperargininemia in adults and children aged two years and older with Arginase 1 Deficiency (ARG1-D), in conjunction with dietary protein restriction. The accelerated approval was granted based on the therapy’s ability to reduce plasma arginine levels — a surrogate endpoint reasonably likely to predict clinical benefit, according to the company. Continued approval will depend on verification of clinical benefit in a confirmatory trial.
ARG1-D is an ultra-rare inherited disorder affecting an estimated 250 people in the U.S., according to the company. It is caused by deficiency of the arginase-1 enzyme, leading to persistent elevation of plasma arginine and toxic metabolites. Patients are typically diagnosed in late infancy or early childhood and can develop progressive spasticity, seizures, developmental delay, intellectual disability and reduced life expectancy.
ARG1-D’s path to approval was a rocky road. Initial developer Aeglea received a refusal-to-file letter in 2022 on its original BLA. FDA 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 agency also requested additional information relating to chemistry, manufacturing, and controls.
Immedica, which acquired global rights mid-2023, resubmitted the BLA in 2024. However, that submission was met with a complete response letter last year, stating the application cannot be approved in its present form and outlining several major deficiencies across efficacy, dosing/administration, safety, and labeling. The agency recommended that it “conduct a trial that assesses clinical outcomes to validate that plasma arginine and/or its metabolites are predictive of clinical benefit. Conceivably, because plasma arginine alone or in combination with specific metabolites may be considered a reasonably likely surrogate endpoint to predict clinical benefit, it may be acceptable that such a trial would be conducted as a postmarketing confirmatory trial if your application was resubmitted via the accelerated approval pathway.”