Elfabrio Shows Comparable Efficacy to Agalsidase Beta at 2 Years as Treatment for Fabry Disease

New results from the phase 3 BALANCE clinical trial (NCT02795676), published in the Journal of Medical Genetics, demonstrated that Elfabrio (pegunigalsidase alfa-iwxj; Chiesi Global Rare Diseases, Boston, MA; Portalix BioTherapeutics, Carmiel, Israel) was well-tolerated and has comparable efficacy to agalsidase beta. Elfabrio and agalsidase beta are both enzyme replacement therapies (ERTs) approved by the Food and Drug Administration to treat Fabry disease.

BALANCE was a randomized, double-blind, active control study assessing the safety and efficacy of Elfabrio in 77 adult participants (aged 18 to 60 years) with Fabry disease and deteriorating renal function who previously received treatment with agalsidase beta for ≥1 year. Participants were randomized 2:1 to receive either 1 mg/kg of Elfabrio or agalsidase beta every 2 weeks for 2 years. Researchers assessed annualized change in estimated glomerular filtration rate (eGFR) for 2 years as a primary endpoint.

• At the end of the study, 15% of participants who received Elfabrio, and 26% of participants who received agalsidase beta, were found to be antidrug antibody (ADA)positive.
• For participants who were ADApositive, the median eGFR slopes were -2.51 mL/min/1.73m2/year for Elfabrio and 2.16 mL/min/1.73m2/year for agalsidase beta.
• For participants who were ADAnegative, the median eGFR slopes were -2.22 mL/min/1.73m2/year for Elfabrio and 2.16 mL/min/1.73m2/year for agalsidase beta.
• After adjusting for exposure, rates of treatment emergent adverse events and mild or moderate infusion-related reactions were 3.6-fold and 7.8-fold higher, respectively, for the agalsidase beta group compared to the Elfabrio group.

Overall, these findings suggest comparable efficacy between the 2 ERTs with potentially improved tolerability for Elfabrio. Elfabrio’s label contains a Boxed Warning for hypersensitivity reactions including anaphylaxis.

"ERTs can lead to clinically relevant improvements in the natural course of Fabry disease, although disease progression occurs in some cases," said Eric Wallace, MD, Co-Director of the University of Alabama at Birmingham Fabry Disease Clinic and lead author of the publication. "In the BALANCE study, we evaluated patients with deteriorating renal function. The data demonstrate comparable renal efficacy and the potential for improved tolerability with pegunigalsidase alfa-iwxj compared with agalsidase beta."