PRX-102 at Least as Effective as Fabrazyme, Interim Data Show

One year of treatment with PRX-102 (pegunigalsidase alfa), an investigational enzyme replacement therapy (ERT), was at least as effective as Fabrazyme (agalsidase beta) at preventing kidney function decline in adults with Fabry disease, interim data from the BALANCE Phase 3 clinical trial show.

These findings add to the growing body of clinical trial evidence supporting PRX-102, the first plant-based, every-other-week ERT, as a potential new treatment option for Fabry patients.

“The BALANCE study continues as planned through its 24-month treatment duration to support its final analysis,” Dror Bashan, Protalix BioTherapeutics’ president and CEO, said in a press release. Protalix is developing PRX-102 in collaboration with Chiesi Global Rare Diseases.

“Based on the entire clinical development program, which includes the BRIGHT and BRIDGE studies, we believe that PRX–102 has the potential to become an important treatment option for both male and female Fabry patients,” Bashan said.

Protalix and Chiesi plan to file an application with the European Medicines Agency (EMA) this year seeking the approval of PRX-102 for treating adults with Fabry disease.

A similar application was rejected by the U.S. Food and Drug Administration (FDA) in late April due to issues with facility inspections and manufacturing processes. The companies plan to request a type A meeting with the FDA to discuss the path for PRX-102’s approval.

“We look forward to submission of the [regulatory application] to EMA for the European Union and to continuing to work with the FDA toward approval in the United States,” Bashan said, adding that “these regulatory milestones are currently our primary focus.”

Like other ERTs, PRX-102 delivers lab-made alpha-galactosidase A — the missing enzyme in Fabry disease — directly into patients’ bloodstream. But the enzyme, made with Protalix’s plant-based ProCellEx platform, was chemically modified to last longer in the body, potentially allowing less frequent dosing than existing ERTs.

The global BALANCE Phase 3 trial (NCT02795676) is comparing the safety and effectiveness of PXR-102 versus Fabrazyme — an approved ERT marketed by Sanofi Genzyme — in 78 adults with progressive kidney disease.

Participants, all receiving Fabrazyme for at least one year before enrollment, were assigned randomly to either continue on Fabrazyme or to switch to PXR-102 (1 mg/kg), both administered every two weeks for up to two years.

The trial’s main goal is to assess whether PXR-102 is at least non-inferior to Fabrazyme at slowing kidney disease progression, as assessed through the mean annualized change in the estimated glomerular filtration rate.

Secondary goals include changes in heart function, levels of disease biomarkers, pain and use of pain medication, as well as quality of life and safety measures.

The main goal of the interim, one-year analysis was to assess PXR-102 non-inferiority after at least one year of treatment.

The analysis was conducted in two pre-defined sets of patients: the intention-to-treat group, consisting of all 77 patients who received at least one dose; and the per-protocol group, comprised of all 74 patients who completed at least one year of treatment.

The intention-to-treat group included 47 men (61%) and 30 women (39%) with a mean age of 44.3 years.

Interim data showed that PRX-102 was at least not inferior to Frabazyme at slowing kidney function decline in the group of patients who completed at least one year of treatment, but not in those who received at least one dose.

At the time of the analysis, two patients had left the trial due to adverse events, which were deemed related to treatment in one of them. No deaths occurred. Safety data appeared favorable and consistent with what was reported in previous PRX-102 clinical trials.

All patients will continue to receive treatment, without knowing which group they were assigned to, for up to two years. Unblinded final data is expected between April and June 2022.

BRIDGE and BALANCE

In addition to BALANCE, PRX-102’s development program includes two other Phase 3 trials with completed enrollment — BRIDGE (NCT03018730) and BRIGHT (NCT03180840).

The completed BRIDGE evaluated PRX-102’s safety and effectiveness in 22 men and women with Fabry who were treated previously with Replagal (agalsidase alpha) for at least two years, and on a stable dose for at least six months.

Final results showed that PRX-102 was safe and resulted in a slower decline in patients’ kidney function than that observed when receiving Replagal, meeting the trial’s main goal.

The ongoing BRIGHT is testing the safety, pharmacokinetics, and effectiveness of PRX-102 — at a more convenient dose of 2 mg/kg, given every four weeks for up to one year — in 30 Fabry patients previously treated with a stable dose of a commercially available ERT every other week for at least three years. Pharmacokinetics refers to a therapy’s movement into, through, and out of the body.

The trial’s top-line data showed that the once-a-month regimen was well-tolerated and effectively maintained patients’ kidney function, biomarker levels, and quality of life. In addition, 75% of patients reported reduction or stabilization in pain severity.

Final data from this trial, due to conclude in December, is expected later this year.

Two open-label extension studies including patients treated with PRX-102’s every-other-week regimen (NCT03566017) and once-a-month regimen (NCT03614234) in the BRIDGE, BALANCE, and BRIGHT trials are currently ongoing.

“We thank the patients and clinicians participating in our completed and ongoing clinical studies evaluating PRX-102,” said Giacomo Chiesi, head of Chiesi.

“As we plan for [regulatory application] submission in the EU, we remain committed to advancing our development program for PRX-102 in the United States while also making access to therapy available to eligible patients through our U.S. expanded access program,” Chiesi added.

Launched in October, this expanded access program (NCT04552691) provides pre-approval access to PRX-102 to U.S. patients who, in the opinion of their physician, lack satisfactory treatment options and/or could not participate in ongoing Fabry trials.