CARMIEL, Israel—A new contender for the treatment of Fabry disease is moving closer to the finish line, as Protalix BioTherapeutics Inc. recently announced top-line results from its Phase 3 BRIDGE trial of pegunigalsidase alfa (PRX-102).
BRIDGE was a 12-month open-label, single-arm switch-over study to assess the safety and efficacy of pegunigalsidase alfa (PRX-102) 1 mg/kg infused every two weeks. The trial consisted of up to 22 patients with Fabry disease who had previously been treated with agalsidase alfa for at least two years and who had been on a stable dose for at least six months. Twenty-two patients enrolled in the study, two of whom withdrew early due to hypersensitivity reaction to treatment, and of the 20 patients who completed the 12-month treatment regimen, 18 opted to roll over to a long-term extension study for ongoing treatment.
Top-line results demonstrated significant improvement in renal function, as measured by mean annualized estimated Glomerular Filtration Rate (eGFR slope), in male and female patients. The mean slope improved from -5.90 mL/min/1.73m2/year while on agalsidase alfa to -1.19 mL/min/1.73m2/year on PRX-102 in all participants. PRX-102 was well tolerated, with transient adverse events.
Protalix tells DDN that the company, along with its commercialization partner Chiesi Farmaceutici S.p.A., submitted a BLA for PRX-102 on the Accelerated Approval pathway on May 27. BLA approval will trigger a milestone payment from Chiesi to Protalix. In addition, Protalix adds, “Protalix and Chiesi also received an Initial Pediatric Study Plan agreement letter from the FDA for PRX-102, outlining an agreed-upon approach to address the needs of pediatric Fabry patients.”
“Our BRIDGE study, together with our other two ongoing fully enrolled Phase 3 clinical trials—the BALANCE study and the BRIGHT study—represents what we believe to be the most comprehensive and robust Phase 3 clinical program for Fabry disease currently in progress,” said Dror Bashan, Protalix’s president and CEO. “As the first of our three studies to complete Phase 3, we believe the BRIDGE study findings support that PRX-102 has the potential to be an important enzyme replacement therapy for the treatment of Fabry disease.”
BALANCE is a randomized, double-blind, head-to-head, active control study that Protalix hopes will demonstrate PRX-102’s superiority in renal function compared to Sanofi Genzyme’s agalsidase beta, also known as Fabrazyme. The BRIGHT study is an open-label, switch-over study assessing the safety, efficacy and pharmacokinetics of PRX-102 2 mg/kg dosed once every four weeks. It also will evaluate if patients can maintain clinical stability after switching to this dosing regimen from an enzyme replacement therapy, agalsidase alfa or agalsidase beta, dosed every two weeks.
“We previously announced positive interim results from 16 Fabry patients after six 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 alfa on renal function for Fabry patients,” noted Dr. Einat Brill Almon, Protalix’s senior vice president of 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.”
Fabry disease is an X-linked inherited disease characterized by deficient activity of the lysosomal α-Galactosidase-A enzyme, which results in progressive accumulation of abnormal deposits of globotriaosylceramide (Gb3) in blood vessel walls. The body normally breaks down Gb3 with α-Galactosidase-A enzyme, but in Fabry disease Gb3 continues to accumulate, eventually resulting in organ failure. The kidneys, heart and cerebrovascular system are particularly affected by this disease.
Pegunigalsidase alfa (PRX-102) is a plant cell culture-expressed, chemically modified stabilized version of the recombinant α-Galactosidase-A enzyme, and was generated by Protalix’s ProCellEx plant cell-based protein expression system.
“ProCellEx overcomes many of the weaknesses of conventional recombinant protein production while offering significant production, regulatory and cost benefits,” Protalix explains. Those benefits include no risk of “infection by human or animal pathogens,” which in turn means lower investment and maintenance costs.
“ProCellEx has a very broad range of expression capabilities. This technology is uniquely able to produce a broad array of complex glycosylated proteins, some of which are difficult to produce in mammalian, bacterial and yeast cell-based systems. And through this technology, it is possible in certain cases to develop and commercialize recombinant proteins without infringing upon the method-based patents or other intellectual property rights of third parties,” the company adds.