PRX-102 Slows Kidney Disease Progression in Fabry Patients Previously on Replagal

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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PRX-102 Phase 3 results

One year of treatment with PRX-102 (pegunigalsidase alfa), an investigational enzyme replacement therapy (ERT), safely and effectively slowed kidney disease progression in adults with Fabry disease who were previously treated with Replagal (agalsidase alpha), according to final results from the Phase 3 BRIDGE clinical trial.

Data also showed that improvements in patients’ kidney function were accompanied by a reduction in the levels of globotriaosylsphingosine (Lyso-Gb3) — a biomarker of Fabry disease — further supporting the therapy’s potential to lessen disease burden.

Findings were presented through both an oral and poster presentation at the 17th Annual WORLDSymposium 2021, held virtually Feb. 8–12.

Both presentations were titled “Switching from agalsidase alfa to pegunigalsidase alfa to treat patients with Fabry disease: 1 year of treatment data from BRIDGE, a phase 3 open-label study,” and presented by Ales Linhart, MD, PhD, the trial’s principal investigator from Charles University in Czech Republic.

“The final analysis of the BRIDGE Study in Fabry patients previously treated with [Replagal] demonstrates a potential benefit of [PRX-102] on renal function,” Linhart said in a press release.

Being jointly developed by Protalix BioTherapeutics and Chiesi Global Rare Diseases, PRX-102 delivers a lab-made, stabilized version of alpha-galactosidase A (Gal A), the missing enzyme in Fabry disease, to patients. This helps cells break down a fatty molecule called globotriaosylceramide, preventing its toxic accumulation in different tissues and organs, such as the kidneys.

Made with Protalix’s plant-based ProCellEx platform, PRX-102 was chemically modified to last longer in the body, requiring less frequent dosing than existing enzyme replacement therapies.

A regulatory application seeking the therapy’s approval for treating adults with Fabry disease is currently being reviewed under priority status by the U.S. Food and Drug Administration, with a decision expected by April 27. A similar application is expected to be submitted to the European Medicines Agency in the future.

The international open-label, switch-over BRIDGE study (NCT03018730) evaluated the safety and effectiveness of PRX-102 in 22 adults with Fabry (15 men and seven women) who were previously treated with Replagal for at least two years, and on a stable dose for at least six months.

Also an ERT, Takeda’s Replagal is approved for Fabry disease in several countries, including Canada, Russia, the U.K., Mexico, Israel, and many members of the European Union, but not in the U.S.

Participants were screened and evaluated for three months while on Replagal and then switched to PRX-102 (1 mg/kg), administered directly into the bloodstream every two weeks for one year.

The trial’s main goal was to determine PRX-102’s safety through the proportion of patients experiencing treatment-related adverse events. Secondary goals included changes in kidney disease progression — as assessed through the mean annualized change in the estimated glomerular filtration fate (eGFR) — and in the levels of disease biomarkers, such as Lyso-Gb3.

A total of 20 (90.1%) participants, with a mean age of 45.8 years, completed treatment and 18 of them chose to enter a long-term extension study (NCT03566017), in which they will continue PRX-102 treatment for up to four years or until the therapy becomes commercially available.

Interim findings from the first 16 patients completing the study suggested that PRX-102 was well tolerated and effective at slowing the progression of kidney disease in these patients.

Final data from all 20 participants completing the study confirmed the interim results, with one year of PRX-102 treatment resulting in a slower decline in patients’ kidney function than that observed when receiving Replagal — mean annualized eGFR drop of -1.19 vs. -5.9 mL per minute per 1.73 m2.

Notably, following the switch to PRX-102, fewer patients showed moderately progressing or fast-progressing kidney disease, with 60% of patients achieving a stable kidney disease status. Similar kidney-related responses were observed between men and women.

In addition, patients’ lyso-Gb3 levels dropped by 31.5%, with men showing an even more pronounced reduction than women (by 32.4% vs. 29.8%). Of note, men had lyso-Gb3 levels nearly four times higher than women at study entry.

Regarding safety (in all 22 participants), switching to PRX-102 was found to be generally safe and well-tolerated, with most adverse events being mild or moderate in severity. The most common moderate adverse events included common cold, headache, and shortness of breath.

Treatment-related adverse events were reported in five patients (22.7%), leading to treatment discontinuation in two of them (9.1%) due to the development of an immune reaction that was resolved.

Four patients (20%) developed persistent antibodies against the therapy-delivered Gal A enzyme, which were found to effectively suppress its activity in two of these patients, who already had antibodies against Gal A before PRX-102 treatment.

In addition to BRIDGE, PRX-102’s Phase 3 development program includes two other Phase 3 trials with completed enrollment — BALANCE (NCT02795676) and BRIGHT (NCT03180840).