Chiesi Global Rare Diseases announced the publication of results from the Phase 3 BRIGHT study, evaluating Elfabrio (pegunigalsidase alfa-iwxj) in adult patients with Fabry disease. The study, published in the Journal of Inherited Metabolic Disease, assessed the safety and efficacy of Elfabrio 2 mg/kg administered every four weeks over 52 weeks in patients previously treated with agalsidase alfa or beta. The approved dose of Elfabrio is 1mg/kg every two weeks. The regimen of ELFABRIO 2mg/kg administered every four weeks is investigational and not approved by the FDA.
The BRIGHT study was a Phase 3, open-label, multinational, switchover study involving 29 patients (23 men, 6 women). The primary objective was to evaluate the pharmacokinetics, safety, and efficacy of the investigational regimen. Key findings from the study include:
Safety and Tolerability
The study reported no new safety concerns among patients treated with Elfabrio. Thirty percent (9/30) of patients experienced at least one treatment-related adverse event (TRAE), all of which were mild or moderate. Infusion-related reactions (IARs) occurred in 16.7% (5/30) of patients, also mild or moderate in severity. Notably, no patients developed de novo anti-drug antibodies (ADAs), and there were no treatment-emergent adverse events leading to study discontinuation or mortality.
Kidney Function
Median estimated glomerular filtration rate (eGFR) remained stable in the efficacy population, with a change from baseline of -1.9 mL/min/1.73m2/year (-2.4 in males, -0.7 in females) after 12 months of treatment with Elfabrio. This suggests that the treatment did not significantly impact kidney function during the study period.
Plasma Lyso-Gb3 Concentrations
Plasma globotriaosylsphingosine (lyso-Gb3) concentrations, a key biomarker in Fabry disease, were low and stable in women treated with Elfabrio (0/6 ADA-positive). A slight increase was observed in treated men (9/24 ADA-positive) compared to baseline.
Expert Commentary
John Bernat, M.D., Ph.D., Clinical Associate Professor of Pediatrics-Medical Genetics and Genomics, University of Iowa Health Care, and lead author of the publication, stated, "While the trial enrolled patients with heterogeneous clinical manifestations who were followed for only 12 months, results show that 2 mg/kg pegunigalsidase alfa administered every four weeks is generally well-tolerated in stable adult ERT-experienced patients with Fabry disease and that this schedule deserves further exploration through additional research."
Giacomo Chiesi, executive vice president of Chiesi Global Rare Diseases, added, "Chiesi is committed to evaluating additional evidence to confirm the long-term results of this administration schedule."
Ongoing Research
An open-label extension trial is currently underway to provide additional data on the long-term effects of this investigational treatment regimen.
