PRX-102 Improves Kidney Function in Fabry Patients, Preliminary Phase 3 Results Show

Protalix BioTherapeutics‘ investigational therapy PRX-102 (pegunigalsidase alfa) improved kidney function in Fabry disease patients, according to preliminary Phase 3 clinical results.

The company announced that additional positive preliminary data of its BRIDGE clinical trial will be presented during the Canadian Symposium on Lysosomal Diseases, taking place Oct. 5-6 in Sherbrooke, Quebec.

Michael L. West, MD, principal investigator of the trial in Nova Scotia, Canada, will discuss the results in an oral presentation titled “Pegunigalsidase Alfa-a Novel Enzyme Replacement Therapy for the Treatment of Fabry Disease: Preliminary Results from the Phase III Bridge Study.

PRX-102, developed by Protalix, is an investigational enzyme replacement therapy (ERT) that compensates for the lack of the alpha-galactosidase A (αGAL-A) enzyme in Fabry patients.

The absence of αGAL-A leads to the damaging accumulation of two fat molecules — Gb3 and lysoGb3 — in tissues such as the heart, kidneys, nervous system, eyes, and skin.

According to Protalix, PRX-102 is more stable and active than currently available ERTs — Fabrazyme (agalsidase beta), developed by Sanofi Genzyme, and Replagal (agalsidase alpha), developed by Shire — because it was chemically modified to be an improved version of the enzyme.

Previous data from Phase 1/2 studies showed that PRX-102 is safe and prevented kidney and heart dysfunction in Fabry disease patients. Also, results from the ongoing Phase 3 BALANCE study (NCT02795676) have so far demonstrated that PRX-102 is superior to Fabrazyme in stabilizing kidney function, and is less suppressed by pre-existing neutralizing antibodies than Fabrazyme.

Now the company will present preliminary data of the ongoing open-label, switch-over Phase 3 BRIDGE trial (NCT03018730) evaluating the safety and effectiveness of PRX-102 in Fabry disease patients previously treated with Replagal for at least two years.

After an initial three-month period of observation, the participants are switched from Replagal to 1 mg/kg of PRX-102, administered every two weeks for a year.

The preliminary results concern the first 14 enrolled patients (seven men and seven women) who have completed six months of PRX-102 treatment. The patients’ age range is 27-60 years, and 10 of them showed signs of kidney damage at the beginning of the study.

Preliminary data has shown that PRX-102 treatment greatly improved patients’ kidney function by reverting the decline in the glomerular filtration rate — a measure of how well the kidneys are cleaning the blood.

“The unique pegunigalsidase-alfa [PRX-102] characteristics and these preliminary results further support the potential advantage of pegunigalsidase-alfa over the currently available FD [Fabry disease] therapies,” the researchers wrote.

The trial is still recruiting in Canada, Europe, the U.K., and Australia, and aims to enroll up to 22 patients.

PRX-102 was designated an orphan drug for the treatment of Fabry disease by the European Commission in 2017, and was granted fast-track designation by the U.S. Food and Drug Administration this year.