Pegunigalsidase alfa (PRX-102)

Pegunigalsidase alfa (PRX-102)
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Pegunigalsidase alfa (PRX-102) for the treatment of Fabry Disease

About Fabry Disease

Fabry disease is an X-linked inherited disease that results from abnormal deposits of a fatty substance called globotriaosylceramide 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 globotriaosylceramide. The abnormal storage of globotriaosylceramide increases with time and, accordingly, globotriaosylceramide accumulates, primarily in the blood and in the blood vessel walls. The channels of blood vessels narrow, leading to decreased blood flow and decreased tissue nourishment. The ultimate consequences of globotriaosylceramide 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. Fabry disease is generally treated with enzyme replacement therapy (ERT), meaning the replacement of the missing alpha-Galactosidase-A enzyme with a recombinant form of the protein via intravenous infusion once every two weeks.


About pegunigalsidase alfa

Pegunigalsidase alfa is a plant cell culture expressed, and a chemically modified version of, the recombinant alpha-Galactosidase-A protein. Protein sub-units are covalently bound via chemical cross-linking using PEG chains, resulting in a more active and stable molecule compared to the current available versions of the molecule. Pegunigalsidase alfa has demonstrated enhanced circulatory half-life, with higher enzyme activity in target organs affected by Fabry disease.

We believe that these characteristics of pegunigalsidase alfa may potentially lead to better clinical efficacy and an improved safety profile compared to currently available treatments for Fabry disease. It also may potentially enable a treatment option of once-monthly infusions as opposed to bi-weekly infusions.

We are developing pegunigalsidase alfa in two dosing regimens with the goal of meeting two important, unmet needs:

  • Better efficacy for Fabry patients with declining renal function
  • Lowering the treatment burden of bi-weekly infusions by reducing the number of infusions by half.

Pegunigalsidase alfa1mg/kg/every 2 weeks is being investigated to demonstrate safety and superior efficacy in renal function versus the currently used enzyme replacement therapy, Fabrazyme®, for Fabry patients with declining renal function.  

Pegunigalsidase alfa 2mg/kg/ once in 4 weeks will be investigated to demonstrate safety and that patients maintain clinical stability after being switched to this more convenient and potentially better compliant regimen from currently used enzyme replacement therapy regimens dosed bi-weekly.

See “Enzyme replacement therapies in development – preclinical and clinical data and experience with pegunigalsidase alfa”, a presentation by Prof. Raphael Schiffmann.

See “”Progression of Nephropathy in Fabry Patients Receiving Enzyme Replacement Therapy (ERT); Relation to Anti-Drug Antibody (ADA) Status and Proteinuria” — Poster Presentation by Dr. David Warnock at the at the 55th ERA-EDTA Congress, May 2018.

See  “Pegunigalsidase alfa — Novel Enzyme Replacement Therapy for the Treatment of Patients with Fabry Disease: Preliminary Results from the Phase III Bridge Study” – Presentation by Dr. Michael L. West at the 1st Canadian Symposium on Lysosomal Diseases 2018


In the PhaseI/II study, pegunigalsidase alfa has been shown to be active in the plasma for the entire two-week period between infusions. 

This level of enzyme activity in the blood is substantially higher than that seen in currently available enzyme replacement therapies for the treatment of Fabry disease.

Circulatory Half-Life

In the Phase I/II study, pegunigalsidase alfa has demonstrated a half-life of approximately 80 hours. It is a more stable molecule with a significantly longer circulatory half-life than the currently marketed enzyme replacement therapies for the treatment of Fabry disease.


Pharmacokinetic modeling demonstrates longer activity of a single infusion of 2mg/kg of pegunigalsidase alfa compared to two bi-weekly infusions of Fabrazyme® over a 4-week timeframe. 

This may potentially result in a new treatment option addressing the unmet need of less frequent infusions.


Two-year follow-up results from our Phase I/II long-term open label extension trial of pegunigalsidase alfa are available from the 11 patients that were enrolled and treated in the extension trial. The results demonstrate that over a 24-month period, treatment with pegunigalsidase alfa resulted in a continuous reduction in biomarkers for enzymatic activity, continuous stability of renal function, stable cardiac parameters, improvement in gastrointestinal symptoms and a 40% reduction in the Mainz Severity Score Index (MSSI), a means of monitoring disease progression and response to therapy.


Throughout the 24-month follow-up of our Phase I/II long-term open label extension trial, 906 infusions of pegunigalsidase alfa were administered. This amounts to approximately 35 patient years. 

Pegunigalsidase alfa was found to be well tolerated, with 98.6% of adverse events being mild to moderate. 

Pegunigalsidase alfa demonstrated lower immunogenicity: only three of 16 patients (less than 19%) formed anti-drug antibodies (ADA) of which two of these patients (less than 13%) had neutralizing antibodies.

All ADA positive patients turned negative for ADA after 12 months of treatment. 

Lower immunogenicity means that the drug provokes a lower immune response. As such, patients treated with pegunigalsidase alfa may potentially experience fewer side effects or potentially experience less inactivation of the therapeutic activity of the enzyme in cases where the anti-drug antibodies are neutralizing antibodies.


Preliminary results of our Phase III BRIDGE study show improved kidney function following switch to pegunigalsidase alfa.

Pivotal Studies

Balance logo

The BALANCE Study is a randomized, double blind, active control study of pegunigalsidase alfa, 1mg/kg infused every two weeks, compared to Fabrazyme® in Fabry patients previously treated with Fabrazyme®. The objective of the study is to demonstrate superiority of pegunigalsidase alfa in renal function by comparison of the eGFR slope (mean annualized change) between treatment groups.


The BRIDGE study is an open-label, single arm switch-over study to assess the efficacy and safety of pegunigalsidase alfa, 1 mg/kg infused every two weeks, in Fabry patients currently treated with Replagal®.


The BRIGHT study is an open-label switchover study to assess the safety, efficacy and pharmacokinetics of pegunigalsidase alfa 2 mg/kg administered every 4 weeks in Fabry patients previously treated with an enzyme replacement therapy: Fabrazyme® or Replagal®.

Clinical Studies

You may be eligible to enter one of our clinical studies with our new enzyme replacement therapy for Fabry disease.

Learn more