PRX-102 (pegunigalsidase alfa) is an investigational enzyme replacement therapy for Fabry disease that was developed by Protalix BioTherapeutics.

How PRX-102 works

Fabry disease is a genetic condition where patients lack the enzyme called alpha-galactosidase A, which is responsible for breaking down a fat molecule called globotriaosylceramide (Gb3 or Gl-3). Patients with Fabry disease have widespread blood vessel damage due to accumulated Gb3. This can lead to kidney, heart, brain, and nerve problems, and increase the risk of stroke.

PRX-102 consists of recombinant alpha-galactosidase A enzyme administered as an infusion directly into the bloodstream. It aims to replenish levels of this enzyme in people with Fabry disease. PRX-102 is made with Protalix’s plant-based ProCellEx platform.

The treatment is currently being investigated as a therapy that may reduce the number of required enzyme infusions to once a month, compared to existing enzyme replacement therapies that need to be administered every two weeks.

PRX-102 in clinical trials

An open-label, Phase 1/2 clinical trial (NCT01678898) found that 0.2 mg/kg, 1 mg/kg, and 2 mg/kg doses of PRX-102 given every two weeks was able to maintain consistent alpha-galactosidase A enzyme levels in the blood. Patients were given PRX-102 for three months and were also monitored for side effects, kidney function, Gb3 levels, and pain.

An extension study (NCT01769001) where patients continued their allocated dose of PRX-102 for another nine months, produced the same results. Both the Phase 1/2 trial and its first extension ended in 2016.

Another open-label extension trial (NCT01981720) is still ongoing where patients who have completed the Phase 1/2 trial and its first extension trial receive 1 mg/kg of PRX-102 every two weeks for up to five years. The trial is enrolling participants by invitation only and is expected to be completed in 2021.

Two-year interim data that included 16 patients from the first two completed trials and 11 from the ongoing extension trial revealed that PRX-102 was well-tolerated, with most side effects being mild to moderate.

Patients had stable kidney and heart functions, improved gastrointestinal symptoms, and a 40% reduction in disease severity. Only 19% of the Fabry patients developed antibodies against PRX-102, but these disappeared after one year of treatment. Antibody formation is a problem while receiving enzyme replacement therapy and may hamper the effectiveness of the treatment.

Three Phase 3 clinical trials are currently underway to compare PRX-102 with existing enzyme replacement therapies for Fabry disease. Investigators are assessing various aspects of Fabry disease and PRX-102 in these trials.

The open-label Phase 3 BRIDGE study (NCT03018730) is recruiting up to 22 patients with Fabry disease have been taking Replagal (agalsidase alfa) for at least two years and had a stable dose for the last six months. After an initial three months of observation, patients will be switched to 1 mg/kg of PRX-102, which will be administered every two weeks for a year. The trial is currently recruiting in Australia, Canada, Europe, and the U.K.

The Phase 3 BALANCE trial (NCT02795676) will compare 1 mg/kg of Fabrazyme (agalsidase beta) with 1 mg/kg of PRX-102 taken twice a month for two years. Enrolled patients had to be already taking Fabrazyme for a year and on a stable dose for the last six months and will be randomized to one of the two medications. The trial is recruiting participants in various countries.

The open-label BRIGHT trial (NCT03180840) is another switchover study for patients who have been taking either Frabrazyme or Replagal for three years. It will switch them to 2 mg/kg of PRX-102 given once a month for one year. The trial is recruiting Fabry disease patients in the U.S., Canada, and Europe, including the U.K.

All three Phase 3 clinical trials are planned to end in 2019.

More details

PRX-102 was granted orphan drug designation by the European Commission in December 2017. In 2018, the U.S. Food and Drug Administration granted fast-track designation to PRX-102, a move that will speed up the development and review process of the drug.

In October 2017, Protalix licensed PRX-102 to Italy-based Chiesi Group for all markets outside the U.S.

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