PRX-102 Shown to Safely Improve Kidney Function in Adults With Fabry

PRX-102 (pegunigalsidase alfa), an experimental enzyme replacement therapy (ERT) for Fabry disease, safely led to significant improvements in kidney function and slowed the progression of kidney disease in men and women previously treated with Replagal (agalsidase alfa).

These are the final results from the open-label Phase 3 BRIDGE trial (NCT03018730), which is expected to support a future marketing authorization application for PRX-102 in Europe.

“We are excited to have completed the final analysis of our Phase III BRIDGE study,” Dror Bashan, president and CEO of Protalix BioTherapeutics, the therapy’s developer, said in a press release.

“We anticipate that the BRIDGE study results will be used to support the filing of a Marketing Authorization Application (MAA) with the European Medicines Agency, and having completed the analysis, we have taken an important step in the preparations for the application,” Bashan added.

PRX-102 is a man-made version of the enzyme alpha-galactosidase A, which is missing in people with Fabry disease. The therapy aims to increase the levels of alpha-galactosidase A to help patients’ cells break down a fatty molecule called globotriosylceramide (Gb3), effectively preventing it from building up in different tissues and organs, and causing damage.

This investigational ERT uses Protalix’s proprietary ProCellEx technology platform, a plant cell-based system that is able to generate man-made enzymes. It was originally developed by Protalix, and then licensed to Chiesi Global Rare Diseases for all global markets.

BRIDGE is one of the three clinical trials making up PRX-102’s Phase 3 development program. It was designed to assess the safety and efficacy of PRX-102 in 22 adults with Fabry disease who were previously treated with Replagal, an approved ERT marketed by Takeda Pharmaceuticals.

To be eligible to participate in BRIDGE, patients must have been treated with Replagal for at least two years, and remain on a stable dose of the medication for a minimum of six months.

During the trial, participants received an intravenous infusion of PRX-102 at a dose of 1 mg/kg, every two weeks, for a total of one year. After completing the trial, participants were given the option to continue treatment with PRX-102 for an additional period of one year in a long-term extension study.

From the 22 patients enrolled in BRIDGE, 20 completed the study, and 18 enrolled in the extension study and are still being treated with PRX-102.

Top-line data from BRIDGE showed that in the overall population of patients in the study, the mean annualized estimated Glomerular Filtration Rate — a measure of kidney function — improved from a yearly loss of 5.90 milliliters per minute per square meter (mL/min/1.73m²) while on Replagal, to 1.19 mL/min/1.73m² after one year of treatment with PRX-102.

Similar improvements in kidney function were observed for male and female participants.

Final data from BRIDGE confirmed all patients who completed the study experienced significant improvements in kidney function, as previously reported. Moreover, study findings showed the number of patients with progressing or fast progressing kidney disease dropped after switching treatment, with the majority attaining a status of stable disease after starting on PRX-102.

Safety assessments indicated PRX-102 was generally well-tolerated. All reported side effects were temporary and did not cause any long-term impacts, and most were either mild or moderate in severity. The most common side effects observed in BRIDGE were nasopharyngitis (common cold), headache, and dyspnea (shortness of breath).

Two patients discontinued treatment after experiencing a hypersensitivity reaction, which was then resolved. Additional analyses also indicated four patients developed persistent antibodies against the therapy, and in two of them, these antibodies were found to block the activity of PRX-102.

“These important final results confirm the topline results announced last May,” Einat Brill-Almon, PhD, senior vice president and chief development officer of Protalix, said.

In addition to BRIDGE, two other clinical trials — BALANCE (NCT02795676) and BRIGHT (NCT03180840) — are part of PRX-102’s Phase 3 development program.

BALANCE is assessing if PRX-102 might be superior to Fabrazyme (agalsidase beta), an approved ERT marketed by Sanofi Genzyme, at improving kidney function when given over the course of two years. Interim results from this study are expected in the coming months.

BRIGHT is evaluating the safety, efficacy, and pharmacological properties of PRX-102, when administered once a month, at a dose of 2 mg/kg, in patients previously treated with Replagal or Fabrazyme. The study’s treatment period concluded in July 2020, and final data is expected to be announced soon.

“We look forward to the continued findings from our other ongoing Phase III studies of PRX-102, with the final results from the BRIGHT study expected in the first quarter of 2021, and interim results from the BALANCE study expected in the first half of 2021,” Almon said.

Last year, Protalix and Chiesi submitted an application requesting the approval of PRX-102 for the treatment of adults with Fabry in the U.S. This request for approval — in the form of a biologics license application — was accepted for review under the Food and Drug Administration’s accelerated approval program and given priority review. At the time, the agency set Jan. 27 as a deadline to announce its final decision, which has now been postponed to April 27.

“We continue to be encouraged by the clinical data generated by this robust Phase III program and look forward to advancing through the final stages of the regulatory review process in the U.S.,” Giacomo Chiesi, head of Chiesi Global Rare Diseases, said.