Pegunigalsidase alfa (PRX-102)
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 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 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 our latest presentation “One-year follow up of Fabry disease patients treated by IV administration of a plant derived alpha-Gal-A enzyme: safety and efficacy“, a presentation by Dr. Derralynn Hughes.
Clinical data from Phase I/II Study
MORE THAN 14 DAYS OF ACTIVE ENZYME
In clinical trials, 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.
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.
POSITIVE IMPACT ON KIDNEY FUNCTION, CARDIAC FUNCTION AND PAIN
Results of our Phase I/II study of pegunigalsidase alfa show a stability in eGFR (estimated glomerular filtration rate) levels of patients from baseline (BL) through 6 months and 12 months of treatment with the drug. eGFR measures level of kidney function and determines a patient’s stage of kidney disease and function. Consistent eGFR levels means that a patient’s kidney function does not deteriorate.
Results of our Phase I/II study of pegunigalsidase alfa also showed stability in key parameters relating to cardiac function.
In addition, results of the Phase I/II study showed that patients experienced less pain while undergoing treatment with pegunigalsidase alfa.
FAVORABLE SAFETY AND TOLERABILITY
Throughout the Phase I/II trial, 417 infusions of pegunigalsidase alfa were administered. This amounts to approximately 16 patient years.
Pegunigalsidase alfa was found to be well tolerated, with 98% of events being mild and moderate.
Pegunigalsidase alfa demonstrated lower immunogenicity: only three patients (19%) tested positive for treatment-induced anti-drug antibodies.
Lower immunogenicity means that the drug provokes a lower immune response. As such, patients may potentially experience less side effects.
FIRST-IN-CLASS; ONCE-MONTHLY ADMINISTRATION
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.
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®.
Enrolment will soon begin for our BRIGHT study. 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®.