Four years after the FDA issued its most heavy-handed form of a rejection to the prior company behind pegzilarginase, the U.S. regulator has now given the treatment a thumbs-up.
Scoring the accelerated nod is Immedica Pharma for Loargys as a therapy for hyperargininemia in the ultrarare genetic disorder Arginase 1 deficiency (ARG1-D). The approval covers patients age 2 and older, with the therapy to be used in conjunction with a protein-restricted diet.
Loargys, which is also known as pegzilarginase, is a recombinant human enzyme designed to lower levels of arginine in patients who are unable to break down the amino acid. It is the first treatment to address the elevated levels of plasma arginine associated with the disorder.
The approval also comes after the FDA issued a complete response letter (CRL) to the company in August of last year citing major deficiencies across efficacy, dosing/administration, safety and labeling.
ARG1-D affects an estimated 250 people in the U.S., with the current standard of care relying on symptom management including diet restrictions, arginine-free amino acid supplementation and nitrogen scavenging agents.
Patients are often diagnosed in late infancy or early childhood, and the symptoms include spasticity, seizures and intellectual disability.
“The accelerated approval of Loargys offers a fundamentally new approach that addresses the enzyme deficiency itself,” Stephen Cederbaum, M.D., a professor of human and medical genetics at the University of California, Los Angeles, said in a release. “Since persistently elevated arginine and its metabolites have been reported to be the proximal or direct driver of disease progression, this is a major advancement in metabolic medicine.”
The company expects to make Loargys—which is infused or injected weekly—available in the U.S. in April.
The green light comes after the FDA dismissed a marketing application for pegzilarginase in 2022 from Texas-based Aeglea BioTherapeutics, handing down a refusal-to-file (RTF) letter. An RTF is issued when the agency determines an application cannot be reviewed due to deficiencies that cannot be quickly resolved.
A year after the rejection, Aeglea sold pegzilarginase to its European partner Immedica for $15 million upfront and $100 million in potential milestones.
While a clinical trial of pegzilarginase linked it to an 80% reduction in mean plasma arginine compared to placebo, there were questions about whether it improved the health of patients. While mobility scores for patients improved in the treatment arm and worsened in the placebo group, the difference fell short of statistical significance.
To ultimately gain FDA approval of Loargys, Immedica relied on results from the same trial, while also submitting additional "long-term data," it said in an email.
"The application was resubmitted with additional data, analyses and clarifications addressing each of the FDA’s objections in the refusal to file and advice in regulatory interactions, which ultimately supported the agency’s decision to accept the filing for review," the company added.
Additionally, in the August CRL, the FDA suggested the possibility of an accelerated-approval pathway "only with a postmarketing confirmatory trial designed to validate surrogate endpoints and demonstrate clinical benefit."
In December 2023, Sweden-based Immedica earned marketing approval of Loargys from the European Medicines Agency. The private company, which was established in 2018 by Nordic investment firm Impilo, does not report sales of its products.
At the end of 2024, Immedica acquired troubled Marinus Pharmaceuticals and its seizure medicine Ztalmy, which was approved in 2022.
Editor's note: Immedica's responses to questions about how it ultimately gained FDA approval of Loargys were added to the story after it was initially published.