From The Editor | May 14, 2020

Inside Protalix BioTherapeutics' Phase 3 BRIDGE Study


By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1

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Protalix BioTherapeutics is 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 Phase III BRIDGE open-label, switch-over clinical trial met main objectives for safety and efficacy. The company recently released topline analysis indicates substantial improvement in renal function as measured by mean annualized estimated Glomerular Filtration Rate (eGFR slope) in patients switched from agalsidase alfa to pegunigalsidase alfa (PRX-102). A decline trend in patients’ renal function on agalsidase alfa was attenuated and improved to be like normal renal function decline when switched to PRX-102. Protalix’s CEO and President, Dror Bashan and Senior VP, Product Development, Einat Brill-Almon answered my questions about the significance of the positive topline results, the role ProCellEx plays in the study, and more.

What is the significance of the positive topline results from the Phase III BRIDGE open-label switch-over study of pegunigalsidase alfa for the treatment of Fabry disease?

The importance of the result is that substantial improvement in annualized eGFR slope from pre-switch to post-switch after 12 months of treatment was observed with a clinically relevant mean change. This switch from Replagal® to pegunigalsidase alfa indicates that pegunigalsidase alfa is well tolerated, with all adverse events being transient in nature without sequelae.

The data was generated from patients who showed a continuous deterioration in kidney function while treated with Replagal measured by the negative eGFR slope over 2 years of treatment before switching to pegunigalsidase alfa, and showed an improved and/or attenuated kidney function and the eGFR overall slope became positive. This change in kidney function was demonstrate in both male and females.  Moreover, Lyso Gb3, an acceptable Fabry disease biomarker, continues to decline after the switch from Replagal to pegunigalsidase alfa further indicating the positive treatment effect of pegunigalsidase alfa. Last, but not least, the safety profile observed in the study indicate good tolerability of pegunigalsidase alfa. These results provide strong support for the potential use of pegunigalsidase alfa to address the still unmet clinical need of Fabry patients and the potential to experience positive potential benefits in relation to renal function in general and in “progressors” in particular. The results further support the design of the BALANCE study and its potential to improve/attenuate deterioration of the kidney functions in Fabry patients with progressing kidney deterioration.

The results of this interim analysis showed that pegunigalsidase alfa is an effective and well tolerated treatment in adult Fabry patients, and is in line with the previous Phase 1/2 study in treatment-naïve Fabry patient population. The BRIDGE study successfully met its main objectives for efficacy and safety with respect to the switch-over from Replagal to pegunigalsidase alfa, as demonstrated by kidney function and evaluation biomarkers follow up.

What is the ProCellEx plant cell-based protein expression system, and what role does it play in the study?

Pegunigalsidase alfa is produced in plant cells in suspension which support a controlled glycosylation profile and a mammalian virus-free production system. In its post-purification form, the plant cell, pegunigalsidase alfa is PEGylated which meets our objective of generating a novel ERT for treating Fabry disease to address the still unmet clinical needs for having a more efficacious and safer Fabry disease therapy. Our design of the enzyme results in greater enzyme stability, an extended bioavailability profile, enhanced uptake in disease relevant tissues, lower immunogenicity, and is applicable for the treatment of the entire Fabry patient population, male sand females, and carrying all mutations. These results further support the intended treatment pattern providing continuous functional enzyme throughout treatment intervals.

From a business perspective, what is significant about the topline results?

The results indicate that switching from the Replagal ERT to the pegunigalsidase alfa ERT demonstrate an improvement in kidney function, representing a potentially significant delay in reaching ESRD in this patient population across genders. The magnitude of the observed treatment effect exceeds the threshold of clinically relevant changes recently recommended in the European Expert Consensus Statement consolidating the therapeutic goals in Fabry disease. We believe that although the trial was designed as an open-label study aiming to show safety, the clinical results will serve as evidence and assist in our penetration campaign vis-à-vis physicians and third-party payers. This is another important piece of the broader clinical program which eventually aims to show superiority in renal function over existing treatments.

What can North American biotechs extrapolate from this news?

The results of the BRIDGE study are an important piece of both our upcoming BLA submission and our MAA submission, supporting the safety and efficacy of pegunigalsidase alfa in the whole spectrum of adult Fabry patient populations.