Spideyboy, thanks for the detailed explanation. I realized a long time ago that cc is a lier with an agenda. But the fact that the SA allows her to spread any lie says a lot about this shitty site. The company could hold a CC and explain, as the PR numbers are hard to understand for most investors.
Protalix BioTherapeutics and Chiesi Global Rare Diseases Announce Topline Results from the 24-Month Phase III BALANCE Clinical Trial of PRX-102 for the Treatment of Fabry Disease
PRX-102 successfully met the primary endpoint on kidney function in active control, non-inferiority study vs. agalsidase beta
Topline results demonstrated a favorable tolerability and immunogenicity profile for PRX-102
BLA resubmission planned for the second half of 2022
CARMIEL, Israel and BOSTON, April 4, 2022 /PRNewswire/ -- Protalix BioTherapeutics, Inc. (NYSE American: PLX) (TASE: PLX), a biopharmaceutical company focused on the development, production and commercialization of recombinant therapeutic proteins produced by its proprietary ProCellEx® plant cell–based protein expression system, and Chiesi Global Rare Diseases, a business unit of Chiesi Farmaceutici S.p.A., an international research focused healthcare Group (Chiesi Group), today announced topline results from the BALANCE pivotal Phase III clinical trial evaluating pegunigalsidase alfa (PRX–102), 1 mg/kg, administered every two weeks, compared to agalsidase beta (Fabrazyme®) for the treatment of Fabry disease. PRX–102 is a novel, PEGylated enzyme replacement therapy (ERT) under development for the treatment of Fabry disease.
Protalix Biotherapeutics Logo Protalix Biotherapeutics Logo "We are pleased to announce positive topline results from the BALANCE Phase III clinical trial and would like to thank the Fabry disease patients and their families, as well as the study investigators and their teams. Our robust clinical development program, from the Phase I\II clinical trial, through the three Phase III clinical trials and the related extension studies, required substantial time and effort from study participants who showed a strong level of commitment allowing our clinical development program to move forward," said Dror Bashan, Protalix's President and Chief Executive Officer. "Based on results from our clinical program, we believe that PRX–102, as a PEGylated enzyme replacement therapy with potentially two different dosing regimens, may be a valuable new treatment option for individuals suffering from Fabry disease."
The pivotal Phase III BALANCE clinical trial has been completed and topline results from the final analysis are now available. This is a 24–month, randomized, double-blind, active control study of PRX–102 in adult Fabry patients with deteriorating renal function that was designed to evaluate the safety and efficacy of 1 mg/kg of PRX–102 administered every two weeks compared to agalsidase beta. The study enrolled 78 patients who were previously treated with agalsidase beta for at least one year with an estimated glomerular filtration rate (eGFR) slope at screening worse than –2 mL/min/1.73 m2/year. Patients were randomized on a 2:1 ratio for switching to PRX–102 or continuing on agalsidase beta. A total of 77 patients were treated; 52 with PRX–102 and 25 with agalsidase beta.
"This is an important milestone both for the Fabry community and Protalix in a long and productive journey. We thank all of our collaborators for their contributions and support throughout this journey," said Einat Brill Almon, Ph.D., Protalix's Sr. Vice President and Chief Development Officer. "We believe that this multi-year study demonstrates the potential for switching from agalsidase beta to PRX–102 in the treatment of patients with Fabry disease. The study met our pre–defined criteria for non-inferiority of the primary endpoint of kidney function in a head–to–head active comparison on both the Intent–to–Treat (ITT) and Per Protocol (PP) analysis sets. These topline results show that PRX–102 was comparable to agalsidase beta in controlling eGFR decline, which is a key measure of Fabry disease progression, and continue to demonstrate a favorable tolerability profile for PRX–102. Combined with previous Phase III results from our BRIGHT and BRIDGE studies, as well as the results from our Phase I/II study and its long-term extension, we believe we have a compelling and consistent dataset from both treatment–naïve and ERT–experienced patients. Given these results, we plan, together with Chiesi, our commercialization partner, to work with regulatory agencies on the applicable submissions, hopefully bringing PRX–102 to approval as a new PEGylated enzyme replacement therapy for all adult Fabry patients."
As first announced in October 2021, as part of a Type A End–of–Review meeting, the U.S. Food and Drug Administration (FDA), in principle, agreed that the proposed analysis of the BALANCE study demonstrating non-inferiority to agalsidase beta included in the data package for the PRX–102 biologics license application (BLA) resubmission has the potential to support the approval of PRX–102 for the treatment of Fabry disease. Given the changed regulatory landscape in the United States with the full approval of agalsidase beta in March 2021, the primary analysis of the BALANCE study was changed from superiority to non-inferiority, as demonstrating superiority is no longer required under FDA guidelines. The primary endpoint of the BALANCE study compared the eGFR annualized changes (slope) between the two treatment arms in the ITT analysis set (77 patients). The study met its pre-specified primary endpoint and demonstrated that PRX-102 was statistically non-inferior to agalsidase beta.
The median (95% confidence interval) of the eGFR slope in the PRX-102 arm was –2.514 mL/min/1.73 m2/year (–3.788, –1.240) and –2.155 mL/min/1.73 m2/year (–3.805, –0.505) in the agalsidase beta arm, demonstrating a large overlap in the confidence intervals of the two arms. The difference in medians (95% confidence interval) is –0.359 mL/min/1.73 m2/year (–2.444, 1.726). The prespecified non-inferiority margin was met. Topline results in the PP analysis set (72 patients) are consistent with the ITT results.
The study population (ITT analysis set) was composed of 47 males (61.0%) and 30 females (39.0%), with a mean (range) age of 44.3 (18-60) years. The mean duration of prior treatment with agalsidase beta was approximately six years. At baseline, mean (SD) eGFR was 73.33 ml/min/1.73m2 (19.82) and median eGFR was 74.51 ml/min/1.73m2; mean (SD) eGFR slope was –8.21 mL/min/1.73 m2/year (5.88) and median eGFR slope was –7.32 ml/min/1.73m2/year.
Forty-seven (90.4%) patients in the PRX–102 arm experienced at least one adverse event compared to 24 (96.0%) in the agalsidase beta arm. The number of events adjusted to 100 years of exposure is 572.36 events for the PRX–102 arm and 816.85 events for the agalsidase beta arm.
Treatment-related adverse events were reported for 21 (40.4%) patients in the PRX–102 arm compared to 11 (44.0%) in the agalsidase beta arm. The number of treatment-related events adjusted to 100 years of exposure is 42.85 events for the PRX-102 arm and 152.91 events for the agalsidase beta arm.
Usage of infusion pre-medication was tapered down during the study, if possible, for all patients. At baseline, 21 (40.4%) patients in the PRX–102 arm used infusion premedication compared to 16 (64.0%) in the agalsidase beta arm. At the end of the study, only three out of 47 (6.4%) patients in the PRX–102 arm used infusion premedication compared to three out of 24 (12.5%) in the agalsidase beta arm. Even with this reduction in use of premedication, there were fewer reported infusion-related reactions with PRX–102: 11 (21.2%) patients in the PRX–102 arm experienced a total of 13 events compared to six (24.0%) patients experiencing a total of 51 events in the agalsidase beta arm. The number of infusion-related reactions adjusted to 100 infusions is 0.5 for the PRX–102 arm and 3.9 for agalsidase beta arm.
Assessment of anti–PRX–102 antibodies or anti-agalsidase beta antibodies, respectively, in the study indicated that, for the PRX–102 arm, 18 (34.6%) patients were anti-drug antibody– (ADA–) positive at baseline, of which 17 (94.4%) had neutralizing antibody activity. For the agalsidase beta arm, eight (32.0%) patients were ADA–positive at baseline, of which seven (87.5%) had neutralizing antibody activity. At the end of the two-year study, 11 (23.4%) patients receiving PRX–102 were ADA–positive, of which seven (63.6%) had neutralizing antibody activity, while in the agalsidase beta arm six (26.1%) were ADA-positive and all six (100%) had neutralizing antibody activity.
Out of the 78 randomized patients, six patients discontinued the study: out of the five (9.4%) from the PRX–102 arm, one patient withdrew consent prior to the first infusion, two discontinued due to personal reasons, and two due to adverse events (one due to an unrelated adverse event and one due to a treatment–related adverse event); one (4%) patient from the agalsidase beta arm discontinued for personal reasons. There were no deaths.
Considering that in the trial, patients in the PRX-102 arm were exposed for the first time to the novel enzyme tolerability data appear favorable for PRX–102 and in line with what was observed in the previous clinical studies of PRX–102.
"The completion of the BALANCE study (NCT02795676), which represents the key pivotal study of the clinical PRX–102 program, is an important event for people with Fabry disease," said David Warnock, M.D., Professor of Medicine (Emeritus) at the University of Alabama at Birmingham. "As a physician and researcher who participated in the design of this trial, I want to emphasize that the development of this new enzyme replacement therapy (ERT) for Fabry disease has required the engagement and contribution of the patients and physicians who participated in the BALANCE study. This effort is the first randomized, head-to-head comparison in Fabry disease of a new ERT to an established, approved form of ERT. The topline results of the BALANCE study and the entire PRX–102 clinical program indicate that this novel PEGylated ERT has the potential for a long-term clinical benefit for adult Fabry patients. These topline results also indicate that PRX-102 was well-tolerated and support the potential to switch to this novel, investigational ERT from a currently approved ERT. As a physician, I believe having an alternative therapeutic option would be an important landmark, and, pending regulatory approval, will potentially improve access of Fabry patients to ERT."
Of the patients that completed the trial, 69 have opted, with the advice of the treating physician, to continue receiving PRX–102 1 mg/kg every other week in a long-term open-label extension study.
"We are pleased to share these positive topline results from the pivotal Phase III BALANCE study, which represent a significant milestone for our PRX-102 development program and the Fabry disease community," said Giacomo Chiesi, head of Chiesi Global Rare Diseases. "These data are especially encouraging following our recent announcement of the positive final results from our Phase III BRIGHT study of PRX-102 in Fabry disease and bring us one step closer towards potential approval of PRX-102 and launch in several countries as a much needed treatment option for patients. We believe the totality of the data observed suggests a favorable benefit-risk profile for the treatment of adult patients with a confirmed diagnosis of Fabry disease and the data will be included in our planned PRX–102 BLA resubmission to the FDA."
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