Elfabrio slows kidney decline in adults in BRIDGE Phase 3 trial
Most participants opted to enter ongoing open-label extension study
A year of treatment with Elfabrio (pegunigalsidase alfa) is well tolerated and slows the progression of kidney disease in men and women with Fabry disease, according to final published data from the BRIDGE Phase 3 clinical trial.
The enzyme replacement therapy (ERT) from Protalix BioTherapeutics and Chiesi Global Rare Diseases was approved in the U.S. last year for adults with Fabry disease, backed in part by data from this trial.
“The findings from the BRIDGE study indicate that [Elfabrio] is an effective treatment in adults with [Fabry disease] with a favorable safety profile,” researchers wrote.
The study, “Safety and efficacy of pegunigalsidase alfa in patients with Fabry disease who were previously treated with agalsidase alfa: results from BRIDGE, a phase 3 open-label study,” was published in the Orphanet Journal of Rare Diseases. The study was supported by Protalix and Chiesi.
In Fabry disease, a lack of the alpha-galactosidase A (Gal A) enzyme leads to the toxic accumulation of certain fatty molecules, namely globotriaosylceramide (Gb3) and lyso-Gb3, in the body’s organs.
Elfabrio designed to deliver functional version of Gal A enzyme
Formerly known as PRX-102, Elfabrio is designed to deliver a functional version of the Gal A enzyme to Fabry disease patients. It was developed using Protalix’s plant-based platform and is expected to last longer in the bloodstream than other enzyme replacement therapies.
The open-label BRIDGE clinical trial (NCT03018730) set out to evaluate the safety and efficacy of Elfabrio, delivered via into-the-vein infusions (1 mg/kg) once every two weeks, over a year in 22 adults with Fabry disease who had been previously treated with Replagal (agalsidase alfa; 0.2 mg/kg) for at least 2 years.
Patients, including 15 men and seven women, were a mean age of 44, and had first started on ERT at a mean age of 34.8.
For most patients, lyso-Gb3 concentrations continuously decreased over the first nine months on Elfabrio, to levels that were then sustained for up to a year, with a mean decrease of 31%. Likewise, Gb3 concentrations were reduced by about 10%.
While starting concentrations of both molecules were greater in men than in women — as expected based on the known biological effects of Fabry disease — the relative observed decreases were similar.
Before starting on Elfabrio, most participants (65%) were showing significant signs of kidney function deterioration, and 45% were categorized as having fast-progressing kidney disease.
As previously reported, annual losses in the mean estimated glomerular filtration rate (eGFR), which is an indicator of kidney function, were slower after a year on Elfabrio than before the study, reflecting a positive effect of the treatment on kidney function. Specifically, Elfabrio was associated with a relative eGFR improvement of 4.70 mL/min/1.73 m2 / year.
All but two patients experienced a stabilization or improvement in eGFR, with similar changes observed in male and female patients.
45% moved to less severe kidney disease category after year of treatment
After a year of treatment, nine patients (45%) experienced a sufficient change in eGFR to enable them to move to a less severe kidney disease category, three were classified into a more severe category, and the rest experienced no change.
The treatment was found to be well tolerated, with the most common side effects being cold-like symptoms, headache, and breathlessness. Two patients had severe allergic reactions to the treatment, which resolved within one day but required them to discontinue the study. Five people experienced infusion-related reactions.
Five people developed antibodies against Elfabrio after starting the treatment. Moreover, two people had pre-existing antibodies against the enzyme, which were found to have neutralizing activity against the treatment.
Altogether, the findings indicate “some patients may experience clinically meaningful benefit from switching from [Replagal] to [Elfabrio] although a treatment period longer than 12 months would be required to confirm this,” the researchers wrote.
After completing the main trial, most BRIDGE participants opted to receive Elfabrio in an open-label extension trial (NCT03566017) that’s still ongoing. It is expected to finish in 2025.