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 the body. It occurs in one person per 40,000. Patients with Fabry disease 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 so it 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 cerebrovascular system.
Fabry Disease is generally treated by enzyme replacement therapy (ERT), meaning replacing the missing alpha-Galactosidase-A enzyme with a recombinant 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 than the current available versions. PRX 102 demonstrated enhanced circulatory half-life, with higher enzyme activity in target organs affected by Fabry disease.
Protalix believes that this may potentially lead to a better clinical efficacy and an improved safety profile compared to currently available treatments.
Clinical data from Phase I/II Study
14 days of active enzyme
In clinical trials, pegunigalsidase alfa has been shown to be active in the plasma for the entire two weeks between infusions
This level of enzyme activity in the blood is substantially higher than that of currently available enzyme replacement therapies.
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.
Positive Impact on Kidney Function
Results of the Phase I/II study with pegunigalsidase alfa showed a stability in eGFR levels of the patients from baseline (BL) through 6 months and 12 months of treatment with the drug. eGFR (estimated glomerular filtration rate) measures level of kidney function and determines stage of kidney disease and function. Consistent eGFR levels means that the kidney function does not deteriorate.
*Germaine et al; 2015
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
*Fabrazyme prescribing information
POSITIVE IMPACT ON Cardiac FUNCTION
Results of the Phase I/II study with pegunigalsidase alfa showed stability in key parameters relating to cardiac function.
MEANINGFUL REDUCTION IN Pain
Results of the Phase I/II study showed that patients experienced less pain while being treated with pegunigalsidase alfa.
In 2016, we have commenced two pivotal trials to support registration of pegunigalsidase alfa.
The BALANCE Study is a randomized, double blind, active control study of pegunigalsidase alfa (PRX-102) compared to Fabrazyme® in Fabry patients previously treated with Fabrazyme®. The objective of the study is to demonstrate superiority of pegunigalsidase alfa (PRX-102) 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 (PRX-102) in Fabry patients currently treated with Replagal®.