Pegunigalsidase Improved Renal Function in Fabry Disease in Phase 3 Clinical Trial

In the phase 3 Bridge clinical trial (NCT04050137), pegunigalsidase (PRX-102, Protalix BioTherapeutics, Carmiel, Israel) treatment improved renal function in participants with Fabry disease. Pegunigalsidase is a plant cell-expressed recombinant PEGylated crosslinked α-galactosidase-A investigational treatment  for Fabry disease (GLA).

Participants switched from treatment agalsidase to pegunigalsidase had substantially improved renal function. Mean annualized estimated Glomerular Filtration Rate (eGFR slope) was used as the measure of renal function. Consistent with previously announced interim data, pegunigalsidase was well tolerated, with all adverse events being transient in nature without sequelae. Of 22 male and female participants enrolled in the study; 2 withdrew early because of hypersensitivity reactions. The other  participants completed the 12-month treatment and 18 enrolled in a long-term extension study and continue to be treated with pegunigalsidase.

Baseline characteristics of the participants, ranging from ages 24 to 60 years, were as follows: mean eGFR 75.87 mL/min/1.73m2 in males and 86.14 mL/min/1.73m2 in females and plasma lyso-Gb3 mean levels were 51.81 nM and 13.81 nM in males and females, respectively. While lyso-Gb3 levels remain slightly high, particularly within the male cohort, continuous reduction in lyso-Gb3 levels was observed of 19.55nM (32.35%) in males and 4.57nM (29.81%) in females.

"The final analysis of the Bridge study in individuals with GLA previously treated with agalsidase demonstrate a positive potential benefit of pegunigalsidase on renal function," said Dr. Ales Linhart of Charles University in Prague, Czech Republic, a principal investigator in the Bridge study.

"The completion of our phase 3 Bridge study and its subsequent analysis mark a significant milestone towards our goal to establish PRX-102 as a new treatment option for GLA," said Dror Bashan, Protalix's president and chief executive officer. "We are encouraged that the Bridge study successfully met its main objectives for safety and efficacy, and we are further motivated to continue our work in progressing pegunigalsidase."

"We previously announced positive interim results from 16 individuals with GLA after 6 and 12 months in the Bridge study. These final results not only indicate that our findings are durable and consistent with previous analyses, but also demonstrate the important potential benefit of pegunigalsidase on renal function for GLA patients," said Einat Brill Almon, PhD, Protalix's senior vice president, Product Development. "We look forward to the continued findings from our other ongoing phase 3 studies of PRX 102, with the final results from the Bright study expected in the fourth quarter of 2020, and interim results from the Balance study expected in the first half of 2021." 

The Bridge study was a phase 3, 12 month open-label, single arm switch-over study evaluating the safety and efficacy of pegunigalsidase, 1 mg/kg infused every 2 weeks. Up to 22 individuals with GLA previously treated with agalsidase for at least 2 years and on a stable dose for at least 6 months