CARMIEL, Israel & BOSTON—As 2020 came to a close, so did the Phase 3 BRIDGE study of pegunigalsidase alfa in Fabry disease, with Protalix BioTherapeutics, Inc. and Chiesi Global Rare Diseases, a business unit of Chiesi Farmaceutici S.p.A., reporting the final study results. The study was a Phase 3 12-month, open-label, single arm switch-over study evaluating the safety and efficacy of pegunigalsidase alfa, 1 mg/kg infused every two weeks, in up to 22 Fabry patients previously treated with agalsidase alfa, marketed by Takeda Pharmaceutical Company Limited (formerly Shire Plc) as Replagal, for at least two years and on a stable dose for at least six months.
Pegunigalsidase alfa (PRX-102) is a plant cell-expressed recombinant, PEGylated, cross-linked α-galactosidase-A product candidate.
"We are excited to have completed the final analysis of our Phase 3 BRIDGE study," said Dror Bashan, Protalix's president and CEO. "We anticipate that the BRIDGE study results will be used to support the filing of a Marketing Authorization Application with the European Medicines Agency, and having completed the analysis, we have taken an important step in the preparations for the application."
Top-line data were announced in May 2020, at which point the mean annualized estimated Glomerular Filtration Rate (eGFR slope) of the study participants 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 patients. Male patients improved from -6.36 mL/min/1.73m2/year to -1.73 mL/min/1.73m2/year, and female patients improved from -5.03 mL/min/1.73m2/year to -0.21 mL/min/1.73m2/year.
All told, 20 of 22 patients completed the full 12-month treatment duration, and 18 of those chose to continue PRX-102 treatment in a long-term extension study. There was substantial improvement in the final results in terms of renal function as measured by mean annualized eGFR slope in patients who switched from agalsidase alfa to PRX-102. After switching, the number of patients with progressing or fast progressing kidney disease decreased, with most patients achieving a stable status.
PRX-102 was well tolerated, and of the 22 patients enrolled, the majority of adverse events were mild or moderate in severity, and only two patients withdrew from the treatment due to hypersensitivity reaction that was resolved.
"These important final results confirm the top-line results announced last May," stated Dr. Einat Brill Almon, senior vice president and chief development officer at Protalix. "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 first quarter of 2021 and interim results from the BALANCE study expected in the first half of 2021."
The Phase 3 clinical development program for PRX-102 consists of a trio of studies: BRIDGE, BALANCE, and BRIGHT. BALANCE is ongoing, and the treatment period for BRIGHT was concluded in July 2020.
"It is clear that many people who are living with Fabry disease are seeking new treatments," added Giacomo Chiesi, head of Chiesi Global Rare Diseases. "We continue to be encouraged by the clinical data generated by this robust Phase 3 program and look forward to advancing through the final stages of the regulatory review process in the U.S."
In addition to releasing top-line data in May, Protalix and Chiesi Global Rare Diseases also announced that they had submitted a Biologics License Application (BLA) to the FDA for pegunigalsidase alfa for the treatment of adults with Fabry disease via the FDA's Accelerated Approval pathway. The BLA was accepted and PLX-102 was granted Priority Review designation, with a PDUFA date of April 27, 2021.