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Protalix BioTherapeutics and Chiesi Global Rare Diseases Announce Final Results of BRIDGE Phase III Open-Label, Switch-Over Clinical Trial Evaluating Pegunigalsidase Alfa for the Treatment of Fabry Disease
The BRIDGE study was a Phase III 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.
Final results of the data generated in the study showed substantial improvement in renal function as measured by mean annualized estimated Glomerular Filtration Rate (eGFR slope) in both male and female patients who were switched from agalsidase alfa to PRX-102.
Twenty of twenty-two patients completed the 12-month treatment duration. Eighteen of the patients who completed the study opted to roll over to a long-term extension study and continue to be treated with PRX-102.
As announced in
Following the switch to PRX-102, there was a decrease in patients with progressing or fast progressing kidney disease, and most patients achieved a stable status post-switch.
PRX-102 was well-tolerated in the study, with all adverse events being transient in nature without sequelae. Of the 22 patients enrolled in the BRIDGE study, the majority of treatment emergent adverse events were mild or moderate in severity, with two patients (9.1%) withdrawing from the therapy due to hypersensitivity reaction that was resolved. The most common moderate treatment emergent adverse events were nasopharyngitis, headache and dyspnea.
An immunogenicity assessment indicated that four out of 20 patients (20%) developed persistent antidrug antibodies over the course of the study, of which two had neutralizing activity.
Baseline characteristics of the 20 patients that completed the study, ranging from ages 28 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.
"We are excited to have completed the final analysis of our Phase III BRIDGE study," said
The Phase III clinical development program consists of three studies, the BRIDGE study, the BALANCE study and the BRIGHT study. The ongoing BALANCE study is a fully enrolled, randomized, double blind, head-to-head, active control study which aims to demonstrate PRX-102's superiority in renal function as measured by the comparison of the mean annualized change (slope) in estimated glomerular filtration rate (eGFRCKD-EPI) between treatment groups over 24 months of treatment as compared to agalsidase beta, marketed by Sanofi Genzyme as Fabrazyme®. The BRIGHT study is a fully enrolled open-label, switch-over study designed to evaluate the safety, efficacy and pharmacokinetics of PRX-102, 2 mg/kg dosed once every 4 weeks, and to assess whether patients maintain clinical stability as measured by certain Fabry disease parameters after being switched to this regimen from an enzyme replacement therapy (ERT), agalsidase alfa or agalsidase beta, dosed every two weeks. The treatment period of the BRIGHT study was completed in
"These important final results confirm the topline results announced last May," said
"It is clear that many people who are living with Fabry disease are seeking new treatments," said
Additional Details about the BRIDGE Study
Patients in the BRIDGE study were screened and evaluated over three months while continuing agalsidase alfa treatment. Following the screening period, each patient was enrolled and switched from agalsidase alfa treatment to receive intravenous infusions of PRX-102, 1 mg/kg every two weeks, for 12 months. Patients had the option to receive PRX-102 infusions in a home care setting based on infusion tolerability and country regulation.
About Fabry Disease
Fabry disease is an X-linked inherited disease that results from deficient activity of the lysosomal α-Galactosidase-A enzyme resulting in progressive accumulation of abnormal deposits of a fatty substance called globotriaosylceramide (Gb3) in blood vessel walls throughout a person's body. Fabry disease occurs in one person per 40,000 to 60,000. Fabry patients inherit a deficiency of the α-Galactosidase-A enzyme, which is normally responsible for the breakdown of Gb3. The abnormal storage of Gb3 increases with time and, accordingly, Gb3 accumulates, primarily in the blood and in the blood vessel walls. The ultimate consequences of Gb3 deposition range from episodes of pain and impaired peripheral sensation to end-organ failure – particularly of the kidneys, but also of the heart and the cerebrovascular system.
About Pegunigalsidase Alfa
Pegunigalsidase alfa (PRX-102) is an investigational, plant cell culture-expressed, and chemically modified stabilized version of the recombinant α-Galactosidase-A enzyme. Protein sub-units are covalently bound via chemical cross-linking using short PEG moieties, resulting in a molecule with unique pharmacokinetic parameters. In clinical studies, PRX-102 has been observed to have a circulatory half-life of approximately 80 hours. The Company designed PRX-102 to potentially address the continued unmet clinical need in Fabry patients.
About Protalix BioTherapeutics, Inc.
About Chiesi Global Rare Diseases
Chiesi Global Rare Diseases is a business unit of the
About Chiesi Group
To the extent that statements in this press release are not strictly historical, all such statements are forward-looking, and are made pursuant to the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. The terms "expect," "anticipate," "believe," "estimate," "project," "plan," "should" and "intend," and other words or phrases of similar import are intended to identify forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual future experience and results to differ materially from the statements made. These statements are based on our current beliefs and expectations as to such future outcomes. Drug discovery and development involve a high degree of risk and the final results of a clinical trial may be different than the preliminary findings for the clinical trial. Factors that might cause material differences include, among others: failure or delay in the commencement or completion of our preclinical and clinical trials which may be caused by several factors, including: risks that the FDA will not accept an application for accelerated approval of PRX-102 with the data generated to date or will request additional data or other conditions of our submission of any application for accelerated approval of PRX-102; unforeseen safety issues; determination of dosing issues; lack of effectiveness during clinical trials; inability to monitor patients adequately during or after treatment; inability or unwillingness of medical investigators and institutional review boards to follow our clinical protocols; and slower than expected rates of patient recruitment; risks associated with the novel coronavirus disease (COVID-19) outbreak, which may adversely impact our business, preclinical studies and clinical trials; the risk that the results of the clinical trials of our product candidates will not support our claims of safety or efficacy, that our product candidates will not have the desired effects or will be associated with undesirable side effects or other unexpected characteristics; risks related to our ability to maintain and manage our relationship with
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