Approval of PRX-102, Plant-based ERT for Adults, Sought for Europe

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by Patricia Inácio, PhD |

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Protalix BioTherapeutics and its partner Chiesi Global Rare Diseases have applied to the European Medicines Agency (EMA) for the approval of PRX-102 (pegunigalsidase alfa), an investigational enzyme replacement therapy, to treat adults with Fabry disease.

This approval request, in the form of a marketing authorization application, has been validated by the EMA and now will be reviewed by its Committee for Medicinal Products for Human Use (CHMP).

CHMP will make a recommendation on whether PRX-102 should be approved. The EMA will forward this opinion to the European Commission, which typically adopts the EMA’s scientific opinion.

If approved, PRX-102 will be available for patients across the European Union.

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“The submission marks a considerable accomplishment in the development of PRX–102 and is an important step forward in navigating regulatory channels in the European Union,” Dror Bashan, Protalix’s president and CEO, said in a press release.

PRX-102 is a recombinant (man-made) version of the enzyme alpha-galactosidase A (Gal A) — missing or markedly deficient in Fabry patients — developed using Protalix’s proprietary ProCellEx technology platform, which uses plant cells to produce recombinant enzymes.

PRX-102 delivers a working version of Gal A directly into patients’ bloodstream. In this case, however, the enzyme is tweaked to last longer, potentially lowering dosing frequency compared with other enzyme replacement therapies (ERTs).

The companies’ MAA s is supported by data from multiple clinical trials, including recent findings in the ongoing BALANCE Phase 3 trial (NCT02795676), which is comparing PXR-102’s safety and effectiveness to that of Fabrazyme (agalsidase beta) — an approved ERT marketed by Sanofi Genzyme — in adults with Fabry and progressive kidney disease.

Interim, 12-month study data showed that PXR-102 was as effective as Fabrazyme at preventing kidney function decline.

Data from two other completed Phase 3 trials — the BRIDGE (NCT03018730) and BRIGHT (NCT03180840) — also support the application

BRIDGE tested the safety and effectiveness of PRX-102 in adults with Fabry disease previously treated with Replagal (agalsidase alfa), another approved ERT for Fabry disease. Findings showed PRX-102 safely and effectively slowed kidney disease progression in these patients, and lowered levels of globotriaosylsphingosine (Lyso-Gb3) — a Fabry biomarker of — further supporting the therapy’s potential to lessen disease burden.

BRIGHT tested the safety, pharmacokinetics (a therapy’s movement into, through, and out of the body) and effectiveness of PRX-102 in 30 Fabry patients previously on a stable dose of a commercial ERT every other week for at least three years. PRX-102 was infused at 2 mg/kg every four weeks for up to one year.

The trial’s top-line data showed that once-a-month treatment was well-tolerated and successful at maintaining patients’ kidney function, quality of life, and biomarker levels. Many patients (75%) also reported a reduction or stabilization in pain severity.

Findings from a completed Phase 1/2 trial (NCT01678898) in patients not using an ERT and extension studies dosing patients with 1 mg/kg every two weeks were also included in the MAA.

“We believe that the safety and efficacy data demonstrated by PRX-102 in clinical trials strongly supports this application and we look forward to completing the final stages of regulatory review,” said Giacomo Chiesi, head of Chiesi Global Rare Diseases.

A similar application submitted to the U.S. Food and Drug Administration was accepted and granted priority review in September 2020.

The FDA, however, rejected the companies’ request for accelerated approval of PRX-102 in April 2021, citing difficulties in required inspections of Protalix’s manufacturing facility in Carmiel, Israel, and issues in manufacturing processes at a third-party site in Europe among its reasons. A new approval request may be made to the agency.

“We are committed to bringing PRX-102 to market and look forward to providing an alternative treatment option for people with Fabry disease,” Bashan said.