Fabrazyme (agalsidase beta), developed by Sanofi Genzyme, has been used as an enzyme replacement therapy (ERT) in Fabry disease to compensate for the lack of α-galactosidase A (αGAL-A) in these patients.
Patients’ immune systems often “attack” Fabrazyme by producing antibodies against it, leading to therapeutic inefficiencies and a progressive loss of kidney function.
The BALANCE study is a double-blind Phase 3 clinical trial (NCT02795676) comparing PRX-102 with Fabrazyme in terms of kidney function and other clinical outcomes.
The study, which is currently recruiting, has enrolled 37 patients (27 men, 10 women) as of January 2018 who were receiving standard ERT but continued to lose kidney function.
The results were presented in a poster titled “Progression of nephropathy in Fabry patients receiving enzyme replacement therapy (ERT); relation to anti-drug antibodies (ADA) status and proteinuria,” by David Warnock, MD, professor of medicine and physiology at the University of Alabama, during the 55th ERA-EDTA Congress (European Renal Association – European Dialysis and Transplant Association).
Of the 27 male patients, 15 had neutralizing antibodies against Fabrazyme; 14 of those 15 had neutralizing antibodies against PRX-102.
These neutralizing antibodies inhibited the activity of Fabrazyme by 83.6% with only 16.4% of effective enzyme left.
However, only 61.6% of PRX-102 was inhibited, leaving 34.8% of effective enzyme activity. This means more than double the amount of effective enzyme was present in the case of PRX-102 than Fabrazyme.
“There is an unmet medical need in patients with Fabry disease who continue to show progressive loss of renal function despite years of treatment with agalsidase beta [Fabrazyme],” Warnock said in a press release. “The progressive loss of kidney function and proteinuria seen in patients suffering from Fabry disease may be the result of neutralizing antibodies.”
Warnock added that given that PRX-102 (pegunigalsidase alfa) “is less inhibited by pre-existing neutralizing antibodies than Fabrazyme, coupled with its significantly longer half-life, there is the potential for pegunigalsidase alfa to control proteinuria and/or stabilize renal function in patients who have not had an optimal clinical response to agalsidase beta [Fabrazyme].”