Open Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Pegunigalsidase Alfa (PRX-102) in Patients with Fabry Disease

Fabry disease is a progressive lysosomal storage disease that is seriously
debilitating and ultimately life-threatening. It is caused by X-linked
deficiency of the enzyme α-galactosidase A (α-GAL) and affects both males and
females. The disease is characterized by subnormal or absent activity of α-GAL.
Clinical onset of the disease typically occurs during childhood or adolescence
(Schaefer et al., 2009) and will progress to end-stage renal disease (ESRD),
cardiac complications, and cerebrovascular problems in the fourth or fifth
decade of life (Wilcox et al., 2008). Although Fabry disease is a X-linked
disorder, females are also affected and develop manifestations of the disease
due to lack of cross-correction between cells with normal α-GAL activity
(mutated X chromosome is inactivated) and cells with enzyme deficiency
(non-mutated X chromosome is inactivated). The clinical abnormalities in
females are more variable, and of later onset compared to males).
Fabry disease is regarded as a rare disease and it is estimated that 1 in
40,000 males has the disease, whereas the
estimated prevalence in the general population is 1 in 117,000.
Protalix has developed PRX-102, a chemically modified recombinant human
alpha-GAL-A expressed in plant cell
culture. As a result of this modification, PRX-102 exhibits more stabilized
homo dimer with active enzyme over longer
period, extended circulation residence time and enhanced bioavailability of the
enzyme relative to the commercial drug.
Therefore, PRX-102 provides continuous presence of enzyme over the 2 week
dosing interval.

To evaluate the ongoing safety, tolerability, and efficacy parameters of
pegunigalsidase alfa in adult Fabry patients who have successfully completed
studies PB-102-F20 and PB-102-F30, or completed at least 48 months in study
PB-102-F03.

This will be an open-label, multicenter study of 1 mg/kg of pegunigalsidase
alfa intravenous infusion every 2 weeks (±3 days) to evaluate the safety,
tolerability, and efficacy of pegunigalsidase alfa in adult Fabry patients (>=18
years of age).
The duration of treatment will up to 60 months or until pegunigalsidase alfa is
available to the patient, or at the discretion of the Sponsor.
The disease parameters that were evaluated during study PB-102-F20, PB-102-F30
and PB-102-F03 will continue to be assessed in this extension protocol (Study
PB-102-F60).

All patients who completed study PB-102-F20 will be treated in study PB-102-F60
with pegunigalsidase alfa 1 mg/kg every other week. Study PB-102-F20 is an
ongoing double-blind study in which up to 26 patients are treated with
agalsidase beta. To maintain the blinding of study PB-102-F20, the first
infusion in PB-102-F60 of these patients will be administered intravenously
over 3 hours with 2 hours post dosing clinical observation. Subsequent
infusions will be managed according to Appendix 7, primary investigator (PI)
evaluation, and Medical Director approval. Premedication, if used in PB-102-F20
infusions, will be continued with the first infusion in PB-102-F60 and then
tapered down at the PI*s discretion pending the patient tolerability and
according to Appendix 7.
The patient will be able to return to the previous established treatment
format, whether home infusion or through a predefined infusion center, once the
PI and Sponsor Medical Director agree that it is safe to do so.
Patients who completed the PB-102-F30 or PB-102-F03 study can continue the
infusions at the same duration achieved in the previous study but not less than
60 minutes, with post dosing observation time of an additional 60 minutes and
the same premedication if used.
Reduction of the infusion time from 90 minutes to 60 minutes will be done in a
step-wise manner pending tolerability and after medical monitor approval.

Pegunigalsidase alfa has been given to 100 people for a duration of more than a
year, but the specific side effects are not yet well known. The safety profile
of pegunigalsidase alfa however does not seem very different from other Enzyme
Replacement Therapies used to treat Fabry disease.
It is possible that the symptoms will not improve during the study or may even
worsen. Please see the Investigators
Brochure and/or Informed Consent form for an overview of all possible side
effects.