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Protalix BioTherapeutics Announces Positive 12-Month Interim Data From the BRIDGE Phase III Open Label Switch-over Study of Pegunigalsidase Alfa for the Treatment of Fabry Disease
"We previously announced positive preliminary results from 16 patients after six months in the BRIDGE study in
The BRIDGE study is an open label switch-over study evaluating the safety and efficacy of pegunigalsidase alfa (PRX-102), 1 mg/kg infused every two weeks, in up to 22 Fabry patients currently treated with agalsidase alfa (Replagal®) for at least two years and on a stable dose for at least six months. Patients are screened and evaluated over three months while continuing agalsidase alfa treatment. Following the screening period, each patient was enrolled and switched from Replagal treatment to receive intravenous (IV) infusions of pegunigalsidase alfa 1 mg/kg every two weeks for 12 months. Patients have the option to receive pegunigalsidase alfa infusions in a home care setting based on infusion tolerability and country regulation.
The 12-month interim data from the first 16 of 22 adult patients enrolled (9 males and 7 females) demonstrate a mean improvement in kidney function, in both male and female patients, when switched from agalsidase alfa to pegunigalsidase alfa.
One hundred percent of the progressing patients, those with an estimated Glomerular Filtration Rate (eGFR) slope between -5 and -3 mL/min/1.73 m2/year, and 66.7% in the fast progressing group, with an eGFR slope < -5 mL/min/1.73 m2/year, achieved the proposed therapeutic goals goals (eGFR slope ≥ -3 mL/min/1.73 m2/year for progressing patients, and ≥ -5 mL/min/1.73m2/year or more than 50% decrease in progression for fast progressing patients) after switching to pegunigalsidase alfa. The majority of the patients who completed the study rolled over to a long-term extension study, continuing to be treated with pegunigalsidase alfa.
In the study, after one year, the mean annualized eGFR slope improved from -5.10 mL/min/1.73m2/year while on agalsidase alfa to -0.23 mL/min/1.73m2/year on pegunigalsidase alfa. Baseline characteristics of these patients, ages 27 to 60 years, were: mean eGFR 75.45 in males and 85.78 mL/min/1.73m2 in females, annualized pre-switching eGFR slope was -5.04 and -5.18 mL/min/1.73m2/year, in males and females respectively, mean residual leucocytes enzymatic activity 5.9% of lab normal mean in males and 27.9% in females, and plasma lyso-Gb3 mean levels 53.6 and 13.8 nM, in males and females, respectively.
Pegunigalsidase alfa was found to be well tolerated in the study, with all adverse events being transient in nature without sequelae. Most of the patients who were eligible for home care therapy per country regulation were treated under a home care arrangement in which certain of the scheduled infusions were performed at the patients' home.
About Fabry Disease
Fabry disease is an X-linked inherited disease that results from deficient activity of the lysosomal enzyme alpha galactosidase A 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. Fabry patients inherit a deficiency of the enzyme alpha-galactosidase-A, 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 (PRX‑102)
The Company's proprietary pegunigalsidase alfa is an investigational, plant cell culture expressed enzyme, and a chemically modified stabilized version of, the recombinant alpha-Galactosidase-A protein. Protein sub-units are covalently bound via chemical cross-linking using short PEG moeity, resulting in a more stable molecule with different pharmacokinetic parameters compared to the current available versions of the enzyme. In clinical studies, pegunigalsidase alfa has been observed to have a favorable circulatory half-life of approximately 80 hours. In addition, in a Fabry mouse model, pegunigalsidase alfa was observed to have favorable levels of enzyme activity in target organs affected by Fabry disease. The Company designed pegunigalsidase alfa to potentially address the continued unmet clinical need in Fabry patients of continuous disease progression, infusion reaction and immunogenicity.
Protalix is a biopharmaceutical company focused on the development and commercialization of recombinant therapeutic proteins expressed through its proprietary plant cell-based expression system, ProCellEx®. Protalix was the first company to gain
Protalix's first product manufactured by ProCellEx, taliglucerase alfa, was approved for marketing by the
Protalix's development pipeline includes the following product candidates: pegunigalsidase alfa, a modified version of the recombinant human alpha-GAL-A protein for the treatment of Fabry disease, in Phase III clinical trials (BALANCE, BRIDGE and BRIGHT studies); and OPRX‑106, an orally delivered anti-inflammatory treatment, and alidornase alfa for the treatment of Cystic Fibrosis, both in Phase II clinical trials. Protalix has partnered with Chiesi Farmaceutici S.p.A., both in
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: risks related to our ability to identify and complete strategic alternatives on attractive terms or at all within the time period required to regain compliance with the continued listing standards of the NYSE American; risks related to our ability to continue as a going concern absent a refinancing or restructuring; risks related to any transactions we may effect in the public or private equity markets to raise capital to finance future activities; 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
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