|View printer-friendly version|
Protalix BioTherapeutics Announces Positive Topline Results from the 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 (Shire Plc) as Replagal®, for at least two years and on a stable dose for at least six months.
Topline 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. Consistent with previously announced interim data, PRX-102 was found to be well tolerated, with all adverse events being transient in nature without sequelae. Twenty-two patients were enrolled in the study; two of those patients withdrew early from the study due to hypersensitivity reaction, and 20 of the patients successfully 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.
In the study, the mean annualized 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.
Baseline characteristics of the patients, ranging from ages 24 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.
"The final analysis of the BRIDGE Study in Fabry patients previously treated with agalsidase alfa demonstrate a positive potential benefit of pegunigalsidase alfa on renal function," said Dr.
"The completion of our Phase III BRIDGE study and its subsequent analysis mark a significant milestone towards our goal to establish PRX-102 as a new treatment option for Fabry disease," said
"Our BRIDGE study, together with our other two ongoing fully enrolled Phase III clinical trials, the BALANCE study and the BRIGHT study, represents what we believe to be the most comprehensive and robust Phase III clinical program for Fabry disease currently in progress," continued
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.
"We previously announced positive interim results from 16 Fabry patients after six and twelve 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," said Einat Brill Almon, Ph.D.,
As previously announced, the Company and its collaboration partner for PRX‑102,
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.
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; slower than expected rates of patient recruitment; unforeseen safety issues; determination of dosing issues; lack of effectiveness during clinical trials; inability to monitor patients adequately during or after treatment; and inability or unwillingness of medical investigators and institutional review boards to follow our clinical protocols; 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
View original content to download multimedia:http://www.prnewswire.com/news-releases/protalix-biotherapeutics-announces-positive-topline-results-from-the-bridge-phase-iii-open-label-switch-over-clinical-trial-evaluating-pegunigalsidase-alfa-for-the-treatment-of-fabry-disease-301056449.html